Flash! CDE issued the Technical Guiding Principles for Pharmaceutical Research and Evaluation of Specific Human Immunoglobulin.

      In order to standardize and guide the R&D, production and registration of specific human immunoglobulin, and further clarify the technical evaluation standards, under the deployment of National Medical Products Administration, the Drug Testing Center organized and formulated the Technical Guiding Principles for Pharmaceutical Research and Evaluation of Specific Human Immunoglobulin (see Annex).
       According to the requirements of the Notice of the General Department of National Medical Products Administration on Printing and Distributing the Release Procedures of Drug Technical Guidelines (No.9 [2020] of the General Administration of Drug Administration), with the approval of National Medical Products Administration, it is hereby promulgated and shall come into force as of the date of promulgation.
       This is for your information.

       Appendix: Technical Guiding Principles for Pharmaceutical Research and Evaluation of Specific Human Immunoglobulin
National Medical Products Administration yaoshen center
May 20, 2022   
I. Overview

Specific human immunoglobulin (HIG) is a highly effective immunoglobulin preparation prepared from plasma containing specific antibodies.

The sources of plasma include plasma with high titer antibody after the patient recovered from infection with a pathogen, and plasma containing specific antibodies by hyperimmune injection of healthy blood donors, that is, injection of vaccines or other antigens to make the injected people produce antibodies. Specific human immunoglobulin (hereinafter referred to as "special immune product") is an indispensable blood product because it contains specific antibodies with high titer, and its effectiveness in preventing and treating specific diseases is better than that of ordinary human immunoglobulin.

In order to encourage, standardize and guide the research and development of special exemption products, this guiding principle is formulated with reference to the relevant technical requirements at home and abroad and combined with the actual situation in China. This guiding principle is only based on the current technical development and scientific cognition, aiming at the general pharmaceutical research technical requirements of special exemption products. The applicant/holder can also adopt other more effective methods and means according to the actual situation of the research and development of the exempted products, but it should conform to the law of drug research and development and provide scientific and reasonable basis to ensure the safety, effectiveness and controllable quality of the products. 

Second, the scope of application 

These guiding principles are applicable to the special immunity products made of specific antibody plasma obtained by direct screening of specific antibody of plasma donors and active immunization. They have similar product characteristics and pharmacological characteristics, and their pharmaceutical requirements are both common and different. At present, the varieties included in People’s Republic of China (PRC) Pharmacopoeia (hereinafter referred to as China Pharmacopoeia) include hepatitis B human immunoglobulin, rabies human immunoglobulin, tetanus human immunoglobulin, etc. The research and development and registration of special exemption products at home and abroad are shown in Schedule 1, and the modes of administration are divided into intravenous injection, intramuscular injection and subcutaneous injection.

III. General principles 

1. Security. 

Because of the particularity of blood products, there is a potential risk of virus pollution, and virus safety control is the core content of blood products quality control. The collection, inspection, storage, transportation, traceability and the immune requirements of plasma donors of the plasma exempted products shall conform to the provisions of "Plasma for Blood Products Production" in China Pharmacopoeia and "Quality Management Standard for Plasma Collection Stations". It is suggested that screening research on B19 and other pathogens should be carried out according to product characteristics and clinical users, especially some special varieties (such as anti-D immunoglobulin). It is suggested that the applicant/holder cooperate with relevant departments to carry out epidemiological monitoring in the area where the plasma station is located. Actively promote the detection technology of nucleic acid in raw plasma and mixed plasma, and formulate standards and requirements. Special attention should be paid to the epidemic situation and detection methods of new and sudden infectious diseases.

2. Specific antibody screening. 

The accuracy and reliability of specific antibody screening results is the key to ensure the quality of raw plasma. In the case of large-scale production, the amount of single plasma detection involved is large, so it is necessary to establish a suitable antibody titer detection method and fully verify it by the method in the early stage of research and development. Single plasma can be screened for specific antibodies by immunolabeling method, and the correlation between binding titer and neutralization titer can be established. The combined plasma, stock solution and preparation shall be tested for specific antibodies by the method specified in China Pharmacopoeia or the verified method. Usually, based on virus neutralization test (mouse neutralization test, micro-cell lesion count and plaque reduction test), immunolabeling test (enzyme labeling, fluorescence labeling, isotope labeling, etc.), hemagglutination inhibition test, immunodiffusion test, immunoturbidimetry test or other immune/biochemical tests, the research is carried out by quantitative and semi-quantitative methods based on reference materials.

3. Production technology 

The process development of this kind of products can refer to the process of similar products that have been listed, and platform technology can be used. The use of chromatography is encouraged to improve the purity of products, but the selection of chromatographic parameters and the influence of the quality of chromatographic resin on the quality of products should be fully considered, and the inactivation and removal ability of viruses by the process should be paid special attention to. The verification of virus inactivation/removal should meet the requirements of General Principles of China Pharmacopoeia "Virus Safety Control of Biological Products", "Technical Methods and Verification Guidelines for Virus Removal/Inactivation of Blood Products" and technical documents such as ICH and WHO.

Management rules and operating procedures should be established for personnel safety protection and wastes in the production process, bioactive substances and viruses should be inactivated according to proven inactivation treatment methods, and effective protective measures should be taken to protect operators to avoid risks such as virus transmission.

Four, pharmaceutical research and evaluation points 

(1) Raw plasma and materials for production 

1, plasma source and quality control 

Quality control of single plasma: single plasma must meet the relevant quality control requirements issued by the national health administrative department. Raw plasma used for production must have legal sources (plasma station certification documents, etc.) and pass inspection and quarantine, and should have complete reagent data (marketing certification documents, etc.) and screening records (antigens/antibodies/nucleic acids) for screening blood-borne infection markers.

Immune procedure: immune procedure and dosage of antigen used are the key factors to determine the concentration and titer of antibody in plasma. It is necessary to define the immunization methods. For example, when active immunization is carried out with approved vaccines or other antigens, these immunogens should have complete source certification information and batch information. The immunization program should refer to the requirements of vaccine instructions, or be formulated according to the immunogenicity of antigen and the reactivity of plasma donors, but the specific immunization program adopted should prove its safety. Subjects should have full right to know, and at the same time make corresponding countermeasures for possible problems. 

Quality control of mixed plasma: A certain amount of plasma should be mixed, which should meet the requirements of China Pharmacopoeia in combination with product characteristics. At present, ordinary people are required to mix the plasma of at least 1000 plasma donors. Specially exempted products generally require plasma mixing from at least 100 plasma donors, except for some special varieties (such as anti-D immunoglobulin products).

No matter the plasma obtained by active immunization with approved vaccine or immunogen or the plasma immunized after natural infection, the specific antibody content standard of each plasma and combined plasma should be formulated at the time of IND declaration. The plasma whose antibody level is up to the standard is used for plasma production. For varieties that have not been recorded in China Pharmacopoeia, there should be a clear basis and a proven detection method for determining the titer of specific antibodies in raw plasma and preparations. When NDA is declared for the varieties included in China Pharmacopoeia, the antibody titer standard should not be lower than the requirements of China Pharmacopoeia.

2. Raw materials for production 

Strict quality control of raw materials used in the production of special exemption products is a necessary measure to reduce the risk of contamination by exogenous factors or toxic impurities in products and avoid the activation of other factors in plasma. In addition to clear sources, quality standards and inspection reports, raw materials for production should also focus on the use of animal-derived raw materials (such as heparin) and avoid using animal-derived raw materials as much as possible. TSE/BSE risk assessment should be conducted for raw materials used in production. 

When using filter AIDS (perlite, diatomaceous earth, etc.), filter membranes and filter element materials in the separation process, it is necessary to establish appropriate quality control standards according to the requirements of different process stages, control the introduction risk of exogenous factors, control bacterial endotoxin and heavy metals, and formulate reasonable limit requirements. In addition, it is necessary to pay attention to the risk of residues that may be mixed into the final product and potentially harmful to human body, and control them if necessary.

(2) Production technology 

1. Stock solution 

The initial raw material of the special immunity products is raw plasma or plasma components. The modified Cohn method or KistlerNitschmann method can be used to separate the special immunity products, and other methods can also be used for separation and purification, such as octanoate precipitation and chromatography. 

The separation and purification process adopted should ensure that the physicochemical and biological properties of the product and the biological activity of the Fc segment of IgG are well preserved. The production process must avoid or eliminate the pollution of microorganisms (bacteria, viruses) and their metabolites (pyrogens) to the maximum extent. It is necessary to strengthen the control of production process and consider the influence of the removal of filter AIDS and the selection of filter media on the products. It should be paid attention to that IgG fractions obtained by different separation methods may contain higher levels of IgA and IgM. At the same time, attention should be paid to the rationality of sterilization and filtration steps, and the integrity of the filtered membrane should be checked.

It is necessary to specify the amount of slurry for pre-clinical, clinical samples and market-scale samples. Generally, continuous production should be carried out, and the production capacity of each process step should be matched with each other, and the processing should be completed at one time. In each process step, it is the key to determine the process control parameters and scope and meet the requirements. When using ethanol and other precipitation methods, it is necessary to control the quality of ethanol and other reagents, and study the protein concentration, temperature, pH value, ionic strength, treatment time and so on, so as to define the acceptable limit range. In the process of dissolution and precipitation of plasma components, avoiding IgG coprecipitation is the key to improve the product yield, especially the key indexes such as temperature and adding time should be fully studied to investigate the influence on the key quality indexes such as protein purity and molecular size distribution. When chromatographic method is used, it is necessary to optimize chromatographic conditions and determine reasonable parameters according to the nature and concentration of protein in the product, such as the capacity of chromatographic column, ionic strength of feed solution and buffer solution, pH value of buffer solution, flow rate, contact time and temperature, etc. The determination of these parameters should be based on the research data of process development, and limit standards and allowable ranges should be formulated. At the same time, it is necessary to study the cleaning and regeneration (service life) of chromatographic resin, the load of chromatographic column and the extract, especially the use of chromatographic packing with potentially harmful ligands. It is necessary to pay attention to the volume, protein concentration, recovery rate and electrophoretic purity of each separation and purification step, and evaluate the process-related impurities (such as ethanol, sedimentation aid, IgA, aluminum, heavy metal ions, etc.) and product-related impurities.(such as polymers, etc.). If necessary, in order to prove the ability of the process to remove impurities, it may be necessary to use standard addition test to evaluate the ability of the process to remove some potential pollutants. If operations that may affect product quality, such as temporary storage and transportation of intermediate products, need to be supported by necessary stability research data.

Encourage the use of innovative and improved processes (including the improvement of ethanol separation process) to improve the utilization rate of plasma and improve the quality of special exemption products. In the early stage of process development, attention should be paid to the identification of key process parameters, the integrity of process control in different separation stages and the rationality of process parameter setting. If the applicant/holder has already marketed products with the same separation and purification process, and the existing process research data and control parameters can be used for reference, the process verification of three batches of new special exemption products should be carried out. 

Considering the preciousness of plasma resources, the pilot-scale research data suitable for clinical trials can also be used for the declaration of IND stage. However, when applying for NDA, it is necessary to have complete commercial scale research data.

2. Preparation 

Clarify single prescription and batch prescription, and explain the basis of rationality of preparation prescription. Auxiliary materials suitable for medical use should be used, and the stability of the supply chain should be ensured. For accessories from multiple suppliers, it is necessary to carry out full research. For brand-new excipients that have not been used in similar preparations at home and abroad, a comprehensive study should be carried out and related declarations should be made. No bacteriostatic agent shall be added to the special exemption products for intravenous injection. Because some cosolvents (such as polysorbate 80) have the potential risk of causing allergic reaction and hemolysis reaction, safety evaluation should be carried out. The preparation process (such as stirring speed) should be studied. In principle, the preparation of semi-finished products should come from a batch of stock solutions. If different batches of stock solutions are used to prepare semi-finished products, the possible risks should be evaluated.

The temperature of products, the duration of packaging, the temperature and humidity of packaging environment should be controlled. Special exemption products involving freeze-drying technology should have data such as freeze-drying process parameters and freeze-drying curves verified by commercial batches, indicating the influence of freeze-drying technology on product quality, especially on biological activity.

3. Process verification 

For the products exempt from intramuscular injection, it is necessary to determine the process flow and key process parameters before NDA declaration, and continuously produce three batches of products to verify the stability of the process, so as to provide a supporting basis for the products to go on the market. For the special exemption products for intravenous injection, the process flow and key process parameters should be determined as far as possible before the confirmatory clinical trial, and the stability of the process should be verified by continuous production of three batches. If there are differences between clinical trial samples and commercial scale batches in terms of production technology or site, it is suggested to carry out change research, and it is suggested to carry out research and exploration on the worst process conditions at an appropriate stage, and it is necessary to prove that qualified products can be produced under the determined process parameters and quality control limits. If multiple production sites or production lines are involved, verification research should be carried out. 

(III) Virus safety and virus removal/inactivation verification 

The detection of single plasma and mixed plasma should meet the requirements of China Pharmacopoeia, and the number of cases of mixed plasma should meet the sensitivity requirements of the kit/detection method. For anti-D immunoglobulin, the nucleic acid load of B19 virus in plasma should be ensured to be less than <104 IU/ml.

Because of the differences in the ability of inactivation/removal of lipid-coated and non-coated viruses by various methods, it is recommended to use two virus inactivation/removal methods with different mechanisms to carry out verification, and to clarify the technical conditions and control parameters of virus inactivation/removal process steps, including product uniformity, upper and lower temperature limits, inactivation time, filtration pressure/speed/temperature/solution composition/membrane integrity, etc. Attention should be paid to the rationality of setting the position of deactivation/removal process steps. When selecting virus removal/inactivation method, the effect of virus inactivation/removal should be balanced with product activity and general safety. 

It is necessary to consider the potential interaction between inactivation steps, the influence of inactivation process on antibody integrity and clinical efficacy, whether new immunogens are formed and the risk of toxic residues that may be introduced. If the production process changes, which may affect the virus removal ability, it needs to be verified again. In addition, the samples used for inspection should be representative of the process. With the development of technology, some new methods of virus inactivation can also be applied in special exemption products, which need to be proved to be scientific and effective and fully verified.

If the products with the same process steps have been approved and registered, and the virus inactivation/removal process has been verified, the newly declared products will only change the mode of administration, and the products with the same production equipment, process and operation as the original products in commercial batches can not be subjected to virus inactivation/removal process repeatedly on the premise of meeting the relevant technical requirements such as Technical Methods and Verification Guidelines for Removing/Inactivating Viruses from Blood Products and Technical Guidelines for Pharmaceutical Change Research of Listed Biological Products.

In order to ensure the virus safety of the final product, we should consider the setting of plasma station from epidemiological data, strictly select plasma donors, screen plasma and manage the quarantine period, optimize the production process and add virus removal/inactivation steps, and evaluate the virus removal ability of the whole process steps of producing products. To evaluate the virus inactivation/removal ability of the production process and the maximum load of specific virus that may exist in the initial plasma, and to ensure the virus safety of the product to the greatest extent, it is necessary to ensure that the verification includes the worst case.

(D) Quality research and control 

1. Analysis of physical and chemical characteristics 

It is necessary to gradually improve the analysis of physical and chemical characteristics in combination with product types, preparation types and drug development stages. IND declaration can be made based on the preliminary research data of physical and chemical characteristics, and NDA declaration should be made by comparing the physical and chemical characteristics, including antibody integrity, antibody subtype distribution, circular dichroism analysis, etc.

2. Biological activity 

Biological activity research should be fully carried out, and it is suggested to study the correlation between binding titer and neutralization titer detection methods. From the aspects of supporting the rationality of the process and considering the influence of the process on the product, it is suggested to establish a method for detecting the biological function of Fc, and to study the sialic acid content of Fc segment in the development stage. Production technology, antibody titer, IgG polymer, IgG subclass, etc. will affect the results of biological function test of Fc. In addition, it is suggested to analyze the binding ability of Fc segment to immune cell surface receptors, the activation of complement function by Fc segment, and the regulation of phagocytosis.

3. Purity and impurities 

Attention should be paid to the components that affect the function of this kind of products, and the purity is generally not less than 95%. In addition to carrying out research on impurity residues and proving the ability of the process to remove impurities, the impurity level limits of batches at different stages (if there are clinical and commercial batches) should be set reasonably. It is suggested that a sensitive method should be used to control the content of impurity protein. 

Polymers produced during the preparation of special immunity products are related to anti-complement activity (ACA), and the content of IgG polymers should be controlled. In order to prevent patients with congenital IgA deficiency from causing serious allergic reaction after using special immunity products, the content of IgA should be controlled. The content of anti-A and anti-B hemagglutinin should be studied and the limit standard should be established to prevent hemolytic reaction caused by large amount of infusion. Encourage the detection of coagulation activator levels and establish standards. It is suggested that anti-D antibody detection should be carried out for intravenous special immunity products from special plasma sources. In addition, in order to prevent the risk of thrombosis, it is suggested to control the FXIa content of intravenous special immunity products and establish standards.

Encourage the detection of other miscellaneous proteins in blood, such as kallikrein activator, immunoglobulin M, transferrin, albumin, α1- antitrypsin, α2 macroglobulin, haptoglobin, α1- acidic glycoprotein, ceruloplasmin, fibrinogen, antithrombin III, plasminogen, fibronectin and C1 esterase inhibitor.

Special exemption products, especially those for intravenous injection, should also focus on the control of insoluble particles. Insoluble particles can not be metabolized in human body, and it is easy to induce thrombosis if they stay in tiny blood vessels. The content of aluminum should be controlled. Aluminum has potential risks to the central nervous system, bones and other organs, and this risk is related to the infusion dose.

4, quality analysis and standards 

The listed special exemption products should meet the requirements of China Pharmacopoeia, and the rationality of testing items should be fully considered for new special exemption products. Quality standards should be set reasonably according to the characteristics of products with different administration methods, such as intravenous special exemption products, and FXIa factor, aluminum ion and IgA content should be increased.

When applying for IND, special attention should be paid to antibody titer, harmful residues and other related testing items.

When applying for NDA, the quality standards of stock solution, semi-finished products (if any) and preparation should be reasonably drawn up based on the data of various research and development stages and stability inspection, on the basis of statistical analysis of multiple batches, combined with the requirements of China Pharmacopoeia and the situation of similar products, with emphasis on the quality control of potency, and more stringent internal control standards should be encouraged. Advanced and mature methods should be used for titer detection, and various complementary analysis methods should be encouraged for quality control in the early stage of research and development. If auxiliary materials such as maltose, polysorbate 80 and glycine are added to the preparation, it should be controlled in the quality standard of the preparation and its content range should be defined.

5, analysis method and methodology verification 

Combined with the characteristics of products, select a reasonable analysis method and carry out sufficient methodological verification to ensure the feasibility of the method.
At the time of IND declaration, at least the preliminary verification of antibody titer and harmful residue detection method should be completed.

When applying for NDA, a complete analysis method should be established and verified. Clarify the accuracy, precision (including repeatability, intermediate precision and reproducibility), specificity, detection limit, quantitative limit, linearity, range and durability of the determination method. Methods other than those in China Pharmacopoeia should be fully verified when applying for NDA. If the determination method is changed greatly, the scope of re-verification should be determined according to the degree of revision of the method.

Establishment and verification of antibody titer detection methods: research on product-specific antibody titer detection methods and standards should be carried out before research and development. It is suggested to study the correlation between binding titer and neutralization titer detection methods. Try to use the method of China Pharmacopoeia, and try to choose the classic and industry-standard method for those not included in China Pharmacopoeia. Clarify the test operation flow, test parameters, preparation and calibration of work standards and criteria for judging results. According to the antibody titer detection method itself, select appropriate indicators to carry out methodological verification and establish verification scheme. Generally speaking, in terms of linearity, the correlation coefficient of neutralization titer determination method should meet the pre-set acceptable standards. In terms of accuracy, the ratio between the actual titer of neutralizing antibody and the theoretical titer of serum with different dilution times is 1, or the slope of regression line in covariance analysis is parallel. In terms of precision, the coefficient of variation should be controlled within 30% as far as possible. In terms of durability, it is necessary to investigate the effects of cell density (generation), neutralization virus dose, neutralization reaction conditions and time, and different positions of orifice plates on the test results. In order to study the influence of possible degradation products and degradation pathways on titer determination, the samples can be destroyed by accelerated methods such as strong light irradiation, high temperature and high humidity. Encourage the use of working standards as quality control, reduce test interference factors, and improve the accuracy and reliability of results.

Verification of detection methods for hazardous residues: Usually, hazardous residues are at trace level, and the sensitivity of detection methods determines the reliability of the results. Encourage the use of more advanced methods and instruments with higher sensitivity based on the methods in China Pharmacopoeia, and pay attention to distinguish the detection limits of instruments and methods. The obtained detection limit and quantitative limit data must be verified by samples with similar contents.
say
Test process and detection limit results, including accuracy and precision verification data. The linear indexes such as recovery rate (%) and relative standard deviation (RSD%) should be listed as regression equation, correlation coefficient, residual square sum linear graph, etc. The range should be drawn up within 20% of the specified limit according to the preliminary measured data, and in general, various methods with different principles should be used to verify each other. Methodological verification of product-related impurities: Methodological verification shall be carried out according to the requirements of China Pharmacopoeia. If the commercial kit is used for residue detection, it is suggested to study the selection of detection kit (such as IgA detection), and the detection kit should explain the sensitivity, specificity, detection limit, quantitative limit and linear range. In general, the accuracy, precision, linear range, interference test, reference interval and other indicators of the kit should be verified. The variation coefficient of precision should be within 20%, the accuracy deviation should not exceed 10%, the linear range determination coefficient (R 2) should be ≥ 0.98, and the relative deviation of interference test should be less than 10%. Attention should be paid to identify the factors that affect the accuracy of the determination results during the release test of products, such as pH value, PK activity, ionic strength of product solution, reaction temperature, etc., which will affect the determination results of PKA, and low pH conditions may reduce the PKA activity of products. 

6, reference (standard)

The quality control reference of antibody titer should be established according to the requirements of relevant guiding principles. When applying for NDA, it is necessary to clarify the key information such as the source and quality control of reference materials, and the reference materials should be related to the samples used in clinical experiments, paying attention to the accuracy and traceability of assignment. If international/national standards are adopted, the information of standards used (source, batch, etc.) shall be specified. If it is a self-made reference, the preparation process, calibration and stability should be studied.

(5) Stability study 

Stability test runs through the whole product life cycle and is the basis for formulating product standards and expiration dates. The stability test should be carried out in accordance with the China Pharmacopoeia and the relevant guiding principles of stability research of biological products at home and abroad. In the declaration stage of IND, preliminary stability inspection can be conducted to ensure the quality of samples in clinical stage. Complete a comprehensive stability inspection before NDA declaration, select suitable packaging materials, define storage and transportation conditions, and formulate a reasonable validity period. The investigation of influencing factor test and accelerated test should be studied as far as possible until the product is unqualified. Long-term stability investigation should extend the observation time of products as much as possible. In general, the liquid dosage form should be placed upside down and upright for stability test. Products with different closed systems should be tested for stability respectively. If a new production site is introduced to produce intermediate products, unless there are other reasons, the stability research of intermediate products and finished products should be carried out. The activity of Fc segment is an important indicator of the effectiveness of this kind of products, so it is suggested to investigate the related stability. For the special exemption products in liquid dosage form, the thermal stability test should be carried out, and the visible foreign bodies should be checked. The results should meet the requirements of China Pharmacopoeia.

(6) Packaging and sealing container system 

The source and control standard of inner packaging materials should be clarified, and the compatibility and sealing of packaging materials should be studied in accordance with the relevant guiding principles such as Technical Guiding Principles for Compatibility Research of Chemical Injection with Medical Glass Packaging Container (Trial Implementation), Technical Guiding Principles for Compatibility Research of Chemical Injection with Plastic Packaging Materials (Trial Implementation) and the requirements of ICH related guidelines. Extracts, dissolved substances, sloughs, etc. shall meet the limit requirements. Pay attention to the influence of the extract of inner packing rubber stopper and glass bottle on the preparation. 

V. Explanation of nouns

1. Blood Products refer to therapeutic products derived from human blood or plasma, such as human albumin, human immunoglobulin, human coagulation factor, etc.

2. Human Normal Immunoglobulin (HNIG): also known as gamma globulin or multivalent immunoglobulin, is an immunoglobulin preparation separated from healthy human plasma by low-temperature ethanol protein separation method or other approved protein separation methods, including intravenous immunoglobulin, intramuscular immunoglobulin and subcutaneous immunoglobulin.

3. Specific human immunoglobulin (HIG): It is a high titer immunoglobulin preparation prepared from plasma containing specific antibodies. The sources of plasma include plasma with high titer antibody after the patient recovered from infection with a pathogen, and plasma containing specific antibodies by hyperimmune injection of healthy blood donors, that is, injection of vaccines or other antigens to make the injected people produce antibodies. Different from ordinary immunoglobulins, such preparations must have at least one high titer antibody for the prevention and treatment of specific diseases in clinic.

4. Anti-complement Activity (ACA): A substance in serum or tissue fluid that can nonspecific bind to complement and make it inactive, such as protease and ester. 

VI. References (omitted)

Jiang Xin, who is domineering and tearing up her colleagues, is strong in returning to green tea and cutting short hair, is too queen-like.

The discussion of family and workplace in TV series Our Marriage has aroused a lot of enthusiasm. Women not only have to face the pressure from the workplace, but also shoulder the responsibility of supporting their families. How to balance career and family is a difficult puzzle for them.

Dong Sijia, played by Rulu, comes out with bgm. In the eyes of colleagues, she isA strong woman in real life. Work vigorously, pay attention to efficiency, is the leader in the team.

She is not a soft persimmon for anyone to hold. Her opponent wants to take away the project in her hand. A sentence "Experience and connections are more important" can block the opponent’s back road.

Subordinate ability is not good and love to snitch, she directly broke that little mind and let the other party leave.

If there is always a female leader who kills all sides in the workplace, there is no doubt that,Dong Sijia is slay’s presence in the audience..

Jiang Xin, who cut her hair short, is a bit more capable and domineering. In her memory, she is still the "Hua Fei Niangniang" who is not angry and powerful, and has the same majesty and gas field.

This domineering spirit has also continued to Xiao Shede. In education, she is a veritable tiger mother. She devoted all her efforts to cultivating her son, and that perseverance even gave in to the defeat of Nan Li, who always disliked her. Today’s "Our Marriage", different roles, speaking look is still so similar.

There will always be one in the workplace.The fearsome devil.They can be independent in their work and their business ability is a cinch. Looking at the appearance, you will feel that they are unreasonable. When you get close, you will find that there is a soft heart hidden under the hard appearance.

One second, I was still preparing for the roadshow with my colleagues, and the next second, I received a meeting notice from the leaders. When a phone call came, Dong Sijia was about to put down his work and rush to the company without stopping.

Subordinate don’t understand why she is so hard, she just said, "Work is sorrow and joy.",and then the figure disappeared in the downpour. No one can help you solve the problem, only you can rely on at the critical moment.

She seems to be strong, but in fact she has her own principles. After she hired Shen Comet, the partner hesitated and questioned whether Shen Comet was competent. Dong Sijia spoke of the dilemma of women’s survival in the workplace in a few words: if she is gentle, she will be questioned about her ability, and if she is strong, she will be criticized for unscrupulous means.

No doubt about employing people, no doubt about people. She recruited comet Shen because she valued each other’s ability, which had nothing to do with her background and partner. I have to say,If full-time mothers want to return to the workplace, they will inevitably face many difficulties. They need more professional ability and stronger inner strength to deal with possible problems..

Shen Comet has been a full-time mother for her children, and her husband Sheng Jiangchuan is too busy with work to ask about housework. The economy is not independent and can’t get the respect it deserves, so there are naturally more and more problems in life.

Unlike Shen Comet Sheng Jiangchuan’s husband and wife, Dong Sijia and Yuwen Li’s husband and wife are male and female. Dong Sijia is an executive of a financial company, with a successful career and a husband in the family. Everything is perfect and he is a "winner in life" in everyone’s eyes.

Her success can’t be separated from her husband’s full support. However, in others’ eyes, Yuwen Li is touched by his wife’s light, and she only needs to be a "full-time husband" with peace of mind at home.

At the reunion, someone took the opportunity to connote Yuwen Li, which sounded like praising his good eye and capable wife. In fact, it was somewhat disdainful and ironic that he was a "soft rice man". Looking at her husband being pointed at by others, Dong Sijia certainly has to support her husband. Liao Liao said a few words, and Rulu replied angrily to the uneasy and kind-hearted man for her husband, which was a perfect interpretation of domineering and protecting her husband.

Although I am grateful to my husband for his contribution to the family,Dong Sijia will still inevitably show her dissatisfaction with her husband’s career.. Yuwen Li wanted to find another job, but Dong Sijia blocked her husband’s way out on the grounds that he was "poor and disgraceful".

At this point, she is a sexual version of Sheng Jiangchuan. Unconsciously bringing work style into the family will inevitably suffocate people after a long time.

Every time he changes a play, Rulu will change his style. At first, the audience was attracted by the glamorous arrogance of Empresses in the Palace Huafei, and then they loved and hated Fan Shengmei in Ode to Joy, and then they avoided Tian Yulan’s tricks in Xiao Shede.

There are some similarities between Dong Sijia and Tian Yulan in Our Marriage. They are both housewives, but Dong Sijia’s husband is better at housekeeping than Tian Yulan, so that his wife has no worries.

It is said that every family has a difficult experience. If you want to do the homework of marriage well, both husband and wife should manage it carefully.A good marriage is to do addition to achieve the effect of 1+1 > 2.. Without a perfect marriage, getting along for a long time will naturally lead to contradictions. Take a step back from each other, regardless of who pays more, but Qi Xin should work together to run a good family.

A strong marriage is doomed not to last long. Passion retreats, and love and responsibility are the keynote of marriage management.

85,900 cars, Roewe i5, the key is high cost performance.

Middle-aged people tend to be more interested in sedate models. The atmospheric design and exquisite interior are the characteristics of such models, which are excellent choices for going to work or picking up children. If you don’t consider the cost of using the car later when you buy a car, you will regret it afterwards. For example, today’s performance in this respect is worth talking about. Next, let’s take a look with Xiaobian.

Let’s look at the appearance of Roewe i5 first. The front face of Roewe i5 looks very round and lovely, and it looks very concise with the three-piece grille. Then it adopts exquisite headlight design, which has great visual impact. The car is equipped with LED daytime running lights, delayed shutdown and so on. Coming to the side of the car body, the size of the car body is 4676 mm * 1838 mm * 1498 mm. The car adopts fashionable and simple lines, and the side wall gives people a very personal feeling. With large-size thick-walled tires, it gives people a very fashionable atmosphere. As for the rear end, Roewe i5′ s tail line is dynamic and lively, the taillight style is round and lovely, and the unique exhaust pipe is very fashionable.

When you get into the car, the interior looks very delicate, highlighting the layered effect. The steering wheel of the car is well designed and made of plastic, which gives a good grip experience. Take a look at the central control. The car is equipped with a cold touch-sensitive LCD central control screen, which makes the interior style impressive and meets the aesthetic standards of most consumers. The dashboard and the seat are equally eye-catching, the dashboard design is remarkable, and the shape has taken the sports route. The car uses leather seats, which are wide and thick, and the overall comfort and wrapping are not bad.

Roewe i5 is matched with continuously variable transmission (CVT) gearbox, with maximum power of 95KW and maximum torque of 158N.m.

The car is equipped with traction control (ASR/TCS, etc.), Bluetooth /WIFI connection, cruise control, voice control, intelligent key and other configurations, which greatly improves the convenience of using the car.

This class of cars is usually the first choice for most people. First of all, the price is not expensive, and secondly, all the configurations are quite complete, which is still very worth starting with. If you are excited, you may wish to go offline and actually feel it.

About Wolf Warriors 2: 30 behind-the-scenes stories you definitely don’t know.


1905 movie network news Since its release, its box office performance has been rising all the way, creating a new record for many Chinese films. Up to now, the box office of Wolf Warriors 2 has exceeded 4.9 billion, and it is about to enter the 5 billion mark. As the film will be postponed to September 28th, Wolf Warriors 2 may achieve even more impressive box office results in the future.

Fist-to-fist fights, shocking wars, and flesh-and-blood figures … … After watching Wolf Warriors 2, many viewers were full of praise for the film. "I never thought we could make such a blockbuster ourselves.". In fact, behind such a wonderful film is the condensation of 10 months’ painstaking efforts of Jason Wu and the entire crew of 1,700 people. Today, the film released 30 behind-the-scenes stories about Wolf Warriors 2, and many netizens sighed after understanding them, "Wolf Warriors 2 is definitely worthy of such achievements" and "If nothing else, let’s go".

 

1. The script existed before filming, and I wanted to show the world the power of China.

The script of "Wolf Warriors 2" existed before "Wolf Warriors" was turned on. After four years of polishing, the script has written more than a dozen drafts. Jason Wu’s purpose is to let China’s soldiers go abroad, let the world see China’s soldiers’ wit, courage, kindness and responsibility, and let the world see China’s strength.

 

2. The script moves the action guidance

In order to make the war scene more international, Wolf Warriors 2 not only has two action teams, Hongkong and the United States, but also the American team invited Sam Hargrave, the action director from Captain America: Civil War. Sam also said that after reading the script, he was moved by Jason Wu’s passion and ambition for movies and decided to join.

 

3. Cold front is no longer a soldier?

Compared with Wolf Warriors, the biggest difference of the cold front in Wolf Warriors 2 is that he takes off his military uniform and is no longer a soldier. However, in Jason Wu’s eyes, Lengfeng’s yearning and loyalty to the army has not been lost. On the contrary, he has more responsibility than before, not only to protect his compatriots, but also to protect all those who suffered in the war.

 

4. The villain is greatly upgraded, and the contest is more exciting

The villains in Wolf Warriors 2 are also rich and huge, with the participation of not only female snipers, professional wrestlers, but also gun experts. This diversity also gives Jason Wu more space to show his struggle against villains.

 

5. The first China action movie shot in Africa.

The story of Wolf Warriors 2 is set in Africa. The reason for choosing overseas is that China has encountered many things overseas in recent years, especially several incidents of evacuating overseas Chinese, and several incidents of China people being shot and robbed overseas, which made Jason Wu feel that the spirit of China soldiers should go abroad.

 

6. Africa was robbed and brought a gun into the slum.

In order to capture the most authentic scene, the crew of Wolf Warriors 2 went to Africa twice, and was robbed three times and twice. Not only was it robbed in the slums, but the photography team even passed by the robbery gang. It can be said that the off-stage experience filmed in Africa is more wonderful than the play.

 

7. The photographer was paralyzed by a poisonous spider.

In the process of filming in Africa, in addition to being robbed, a photographer of Wolf Warriors 2 was unfortunately bitten by a local poisonous spider, and the paraplegic wound was amazing, which was very difficult.

 

8. Walking in the snowstorm in Iceland, eating snow when you are thirsty.

When shooting in Iceland, Jason Wu and his party walked for several hours in the snow of minus 10 degrees, but they had to eat snow for several hours without drinking water.

 

9. 6 minutes of underwater scenes with one mirror was once considered impossible to complete.

In the movie, what surprised many viewers was a 6-minute scene, including an underwater action scene, which was considered impossible before shooting because no one had ever played underwater for three minutes before. It is the challenge that makes Jason Wu want to break through. When shooting, neither the actors nor the staff had respirators, and there were only five lifeguards to prevent accidents. And this difficult underwater action scene, invited the underwater photographer to take the mirror. When shooting, because you can’t see anything in the water without glasses, everything can only be done by feeling. This action scene was rehearsed for more than half a month and rehearsed underwater for 4 days. Jason Wu spent more than 10 hours underwater every day, which was very hard.

 

10. Hold your breath underwater for 3 minutes, and Jason Wu almost drowned.

In the movie, Jason Wu moves freely and smartly underwater, actually because he is equipped with four kilograms of lead, which makes the diving speed faster. But after two shots, Jason Wu’s body couldn’t help sinking because the lead was too heavy, and his mouth began to soak. Fortunately, the lifeguard swam quickly to Jason Wu’s side, put the respirator on Jason Wu’s face and dragged him ashore. This dangerous scene also made the atmosphere almost tense and solidified.

 

11. Diving from the 13-meter deck, Jason Wu jumped 26 times in a row.

In the movie, the scene of Jason Wu diving from the 13-meter deck is also impressive. Although the shot was only a few seconds, Jason Wu dived 26 times in a row in order to cooperate with the photographer. When shooting in the open sea, because the ocean current velocity was 15m/s that day, Jason Wu was instantly washed away by the ocean current after entering the water, and finally he had to rely on the crew’s speedboat to intercept people.

 

12. Captain America: Civil War villains joined, and the two men fought Wu Jing to be "slapped"

One of the biggest attractions of Wolf Warriors 2 is a five-minute hand-to-hand combat between Jason Wu and the villain "Crossbones" Frank Grillo in Captain America: Civil War. In order to pursue the realism from fist to flesh, Jason Wu gave up the trick and asked Frank to really hit himself in the face with his fist.

 

13. Fight the villain No.2, and shoot at minus 9 degrees repeatedly.

In addition to the fierce hand-to-hand combat with Captain America: Civil War’s villain, another action scene in which Jason Wu was ill against villain No.2 also made many viewers enjoy it. This fight was also very difficult. At night, it was MINUS 9 degrees, and the two still wore short sleeves and repeatedly fought, sometimes even the knife was unstable.

 

14. The car chase in the slums is thrilling, and Jason Wu has no protective measures.

In the movie, the cold front raced in the narrow streets of slums, which made the audience scream for excitement. When filming this drifting scene, Wu Jing hung on a speeding car with one arm, in fact, there was no protective measures at all, and it was very dangerous to rely on the strength of his arm to ensure that he would not be thrown out.

 

15. The real military tank drifts 180, and the tank hits the oil spill.

Sports car drift is common, but tank drift is believed that many people have never seen it. This time in Wolf Warriors 2, Jason Wu staged a tank version of "Speed and Passion", which made real military tanks collide violently. In order to present a shocking and exciting visual picture, Jason Wu personally drove, took several shots repeatedly, and finally hit the tank and leaked oil, which was at risk of explosion at any time.

 

16. Shooting a tank chase scene almost killed Jason Wu.

In the movie, the villain drives a tank and chases Jason Wu’s scene while madly hitting a roadside post, which makes many viewers feel worried about Jason Wu. While filming this scene, Jason Wu was almost hit by a brick on the post. This sudden accident also made him sigh "fortunately, his life is big."

 

17. The explosion scene shocked the big scene, and Jason Wu was temporarily deaf by bombing.

In the movie, the realistic presentation of explosions such as airplanes, tanks and off-road vehicles brought exciting visual experience to the audience, but behind the scenes of shocking scenes, in order to restore the truth, Jason Wu demanded that the explosion shots should be as real as possible, and blew up hundreds of equipment, including one airplane model, two 20-ton tank models and nearly 100 cars. When an explosion scene was filmed, Jason Wu’s ears were blown to temporary deafness, and he really took his life to make a movie.

 

18. WU GANG practiced his gun for 20 days, suffering from "changing the magazine with one hand"

After watching the movie, many viewers were circled by the veteran played by WU GANG. Why did you choose Wu Gang to play it? Jason Wu admits that WU GANG has the spirit and momentum of a veteran. In order to better interpret this role, WU GANG joined the group ahead of time. It took more than 20 days to practice raising a gun. From the beginning, he couldn’t use a gun, but later he could skillfully change the magazine with one hand. This professional attitude also made Jason Wu frankly admirable.

 

19. With a waist injury, WU GANG took painkillers and insisted on filming.

While filming an explosion scene, WU GANG accidentally fell on a big stone and was seriously injured in the waist, so he couldn’t move at all. In order not to delay the filming progress of the crew, after simple treatment, WU GANG insisted on completing the action scene with ice and painkillers.

 

20. Jason Wu invited Yu Nan by phone, and the prison marriage proposal moved the audience.

In the movie, the memories of Leng Feng and Long Xiaoyun moved many audiences, especially the scene of Long Xiaoyun proposing to Leng Feng in prison. The setting of this scene actually represents Long Xiaoyun’s persistence in love and his recognition and encouragement to the cold front. Whether Leng Feng was in prison or left the army, Long Xiaoyun always recognized Leng Feng. It is this recognition that also stimulated the cold front, because one of his carelessness caused an irreparable regret. Off-stage, Jason Wu invited Yu Nan to join again with a phone call and a letter. Besides his sincerity, Yu Nan’s simple and pure attitude towards movies is also an important reason for their second cooperation.

 

21. Celina Jade spent 10 months alone with the crew without an assistant.

Celina Jade once cooperated with Jason Wu. Although Celina Jade put out the fire on the spot, this second cooperation made Jason Wu bluntly "like finding a treasure". When shooting, Celina Jade didn’t even bring his assistant, so he came to the set alone and worked with the crew for 10 months, desperately.

 

22. Xiong Haizi, which Jason Wu arranged for Hans Zhang to play, was actually the most growing role in the film.

In the movie, Jason Wu designed Hans Zhang’s role as a rich second generation Xiong Haizi. Although this character sounds a little unreliable, it is actually the most growing role in the movie. Many viewers said that Xiong Haizi, played by Hans Zhang, was circled after watching the movie. Jason Wu also said that the character changed from a Xiong Haizi to a good boy, and the role was very beautiful, and Hans Zhang’s accomplishment was also very high.

 

23. Yu Qian’s role has a prototype, and he missed the performance for filming.

In the movie, the profiteer played by Yu Qian impressed many audiences. The reason why Wu Jing designed such a role in the film is because he really met such China people who cheated their compatriots in Africa. Yu Qian also completed this role very well, and even failed to catch up with Deyun’s performance for the sake of trick shooting, which is respectable.

 

24. China, an African actress, was born and did not have stage fright at an early age.

The two cute little African actors in the film were actually born in China, one from Shanxi and the other from Hangzhou, and they can speak fluent Chinese. The reason for choosing these two children is precisely because their feelings are very consistent with Jason Wu’s role setting. One is naughty like a grown-up, and the other is simple and shy, and they have no stage fright when they play at an early age.

 

25.1,000-strong crew, with staff from 26 countries.

The crew of Wolf Warriors 2 has a maximum of 1,700 people, including staff from 26 countries. Such a huge crew also made director Wu Jing feel more responsible. During the filming, Jason Wu was most worried that the life of the staff would be in danger because of the different habits and communication difficulties between China and foreign countries in safety measures. And there was a scene in the factory, because there were hundreds of group performances, and the noise was too loud when filming, which also attracted the local police.

 

26. The evacuation bridge section was filmed smoothly, and the feelings were true and natural.

The movie clips about the evacuation of overseas Chinese made many viewers excited, especially the scene of Wu Jing wearing a national flag and crossing the war zone at last. Jason Wu revealed that these scenes were filmed very smoothly, because all the feelings were true, and everyone was naturally proud of the strength of China and the strong motherland behind them. When shooting, a sense of awe arises spontaneously.

 

27. The American team once dared not let Wu Jing use a real gun.

As a military war action film, there are many exciting gun battles in Wolf Warriors 2. While filming, the American action team was afraid to let Jason Wu use the real gun for fear of safety. However, after more than 10 months’ experience in the special forces, Jason Wu dispelled the concerns of the American team by virtue of his professional quality in the safe control of guns.

 

28. Overtime and overspending are serious, and everything is worth it for the movie.

Wolf Warriors 2 is the first China war film to go abroad. With a team of thousands of people and the theme of modern war, the shooting difficulty can be imagined. In order to achieve better shooting effect and film quality, the film overspent and overtime were very serious. The original four-month shooting plan was shot for 137 days in China alone, but for the final presentation effect, everything was worthwhile. Jason Wu also bluntly said that this shooting experience was a valuable life wealth for himself.

 

29. Jason Wu hasn’t been home for 137 days in China.

Although "Wolf Warriors 2" was filmed in China for 137 days, Jason Wu didn’t have time to go home and has been rooted in the crew. Thanks to Iola’s support and understanding, Jason Wu took his son to visit the crew to cheer Jason Wu up.

 

30. I am proud that the film ends with China passport.

At the end of the film, there is a China passport, and a passage on it makes many viewers excited after watching the film. People’s Republic of China (PRC) citizens: When you are in danger overseas, don’t give up! Please remember, behind you, there is a strong motherland! For this design, Jason Wu said in an interview that with the rise of China, China’s passport has become more and more popular in the world. Having a Chinese face is just like having a passport anywhere in the world. For previous evacuees, having a China passport gives you priority, which is an honor. Holding this passport will make you feel very proud.

23 models of Euler Good Cats were upgraded to "electronic arms" at the store.

  [Aika Auto Domestic New Car Original]

  As a masterpiece of the Euler brand in 2023, the 2023 Euler Good Cat launched a total of five models, with the price range of 129,800 yuan to 165,800 yuan. Now new cars have arrived in stores all over the country. The 2023 Euler Good Cat has achieved nine core functional product upgrades, including the brand-new "bar-table" auxiliary instrument panel, electronic shield, V2L external discharge, Michelin high-performance tires, 50W mobile phone wireless fast charging, CN95 air conditioning filter, steering wheel four-way adjustment, Type-C interface and non-stop electronic toll collection system.

 

Great Wall Motor 2023 Euler Good Cat

Great Wall Motor 2023 Euler Good Cat

Great Wall Motor 2023 Euler Good Cat

Great Wall Motor 2023 Euler Good Cat

Great Wall Motor 2023 Euler Good Cat

Great Wall Motor 2023 Euler Good Cat

    

Great Wall Motor 2023 Euler Good Cat

    

Great Wall Motor 2023 Euler Good Cat

Great Wall Motor 2023 Euler Good Cat

  Editor’s comment:Euler Good Cat has been on the market for three years and gained the trust of nearly 130,000 users. This time, through the upgrade of configuration, it will be more competitive. Of course, in addition to these visible changes and upgrades, the 2023 Euler Good Cat has also optimized key performance indicators such as NVH and handling comfort.

Wonderful content review:

12.98-165,800 yuan: 2023 Euler Good Cat went on the market.

2023 Shanghai Auto Show: The New Good Cat GT Mulan Edition goes on sale.

Euler’s struggle for women needs to tell some new stories.

Weir’s high-end CIS products continue to be used in mainstream mobile phone high-end flagship models.

On the evening of March 18th, at the flagship new product launch conference of Glory Spring, the highly anticipated Magic6 to Zhen Edition and Magic6 RSR Porsche designs were officially unveiled. These two flagship mobile phones are equipped with a newly upgraded SLR super-dynamic Hawkeye camera, which brings the world’s first LOFIC technology (full name: lateral overflow integration capacitor) from the vehicle regulation level.

According to people in the industrial chain, LOFIC technology comes from Howell Group (603501.SH), and Glory will use this technology to take the super-dynamic Hawkeye as the main camera and name it H9800. As the world’s first smart phone image sensor with LOFIC technology, a single exposure can achieve a dynamic range close to the human eye level, setting a new industry standard for high dynamic range (HDR) image capture of mobile phone photography.

In an interview with the media, Yu Renrong, chairman of Howe Group-Weir Co., Ltd. said: "LOFIC technology can now basically approach the level of human eyes, enabling mobile phone image sensors to achieve the maximum dynamic range under limited specifications, opening up the imagination of image innovation."

The official micro-signal of Howe Group also introduced this technology. TheiaCel? technology uses the function of LOFIC to provide excellent single exposure HDR even under challenging lighting conditions. The OV50K4050 megapixel image sensor based on TheiaCel? technology adopts 1.2 micron pixel size and 1/1.3 inch optical format, and has the functions of high gain and correlated multiple sampling (CMS), which can achieve the best performance in low light conditions.

The easy-to-understand explanation is that the basic principle is to place a high-density capacitor on each photodiode of the mobile phone image sensor to collect photoelectrons that may have overflowed due to saturation. When the number of photoelectrons converted by the photodiode exceeds the maximum capacity originally, the excess photoelectrons will flow to the adjacent capacitors instead of being "overexposed" because of overflow, which makes the highlight information in the shooting scene better preserved by the sensor and makes the output film closer to reality.

As early as last September, Howe Group introduced the image sensor OX08D10 with LOFIC technology for the automobile market for the first time. With TheiaCel?, OX08D10 can capture HDR images up to 200 meters away, which can achieve the best balance between SNR1 and dynamic range, and is also the best choice for outdoor camera applications. This year, the company introduced this revolutionary technology into the consumer smart phone industry, showing the infinite possibilities of TheiaCel?’s technological innovation.

In recent years, with the changes in the demand structure of the downstream market, the consumer electronics market is undergoing a round of product cycle structure adjustment. According to the research results of consulting firm TechInsights, the demand of mainstream smartphone manufacturers for mobile phones equipped with high-performance cameras is driving the market demand for 50-megapixel CIS products with large pixel size and larger optical format.

In order to meet the market demand, Howe Group has laid out products with different pixel specifications, which can be covered by all categories, and has made significant progress in the high-end CMOS market. The products have been used in high-end flagship smartphones of many domestic head phone brands. Among them, OV50H product is the beginning of the company’s high-end main camera layout, which is widely known for Xiaomi 14 "Light and Shadow Hunter 900". The poster announced by Xiaomi Company shows that the power consumption of "Light and Shadow Hunter 900" is reduced by 42% under the same size. According to the industrial chain information, in addition to Xiaomi, this product is also equipped with rear-mounted main camera sensors on many high-end models such as VIVO iQOO12 series and glory Magic6.

The release of the new image sensor with LOFIC technology of Howell Group is a further breakthrough in the field of high-end flagship machine image sensors, which sets a new performance benchmark for the flagship rear main camera. Industry analysts pointed out that this also shows that the competitiveness of domestic CMOS manufacturers in the high-end market is expected to be widely recognized by mainstream mobile phone manufacturers around the world, and the launch of the company’s series of core product technologies will also reshape the industry’s head pattern. (CIS)

Proofreading: Zhao Yan

Dialogue between Lan Yu and Zhu Yun | He brought A Writer’s Odyssey back.


Special feature of 1905 film network "At the moment when you really get the Golden Rooster trophy, you should have a sense of responsibility and mission that has been passed down in your mind?" Pointing to the trophy in Zhu Yun’s hand.


"Yes, it was the highlight of life and the climax of life." Zhu Liyun’s eyes sparkled and he was lost in memories.


As early as 2015, he was nominated for the Best Editing Award of the 30th Golden Rooster Award for Chinese Films, which was the first year when the Golden Rooster Award was restored to the Best Editing Award. Four years later, he finally won the Best Editing Award in the 32nd Golden Rooster Award of Chinese Film. On the stage, he thanked that person … …


2021 is the 40th anniversary of the Golden Rooster Award in Chinese films. Blue Feather Living Room specially launched a series of interviews on the 40th anniversary of the Golden Rooster Award, looking back on the glorious years of light and shadow, and talking about the future of China films. Zhu Liyun, director of Lan Yu Dialogue, listened to the video creation in the digital age witnessed by the film editor.


"China’s first haircut" is a great god in my heart.


The winner of the 28th Golden Rooster Award for Lifetime Achievement in Chinese Film is called "China’s First Cut", which is the editing god in his heart. Fu Lao’s speech on life when he won the prize is still hit the floor in his heart. "Heaven rewards diligence, everything depends on human effort." This sentence, which the Fu Lao insisted on all his life, has also become Zhu Liyun’s motto. Under the strong appeal of Fu Lao, the Golden Rooster Award for Best Editing was restored in 2015. For this opportunity of "the predecessors planted trees, and the descendants enjoyed the cool", Zhu Liyun was also shortlisted for the Golden Rooster Award for Best Editing Award for his innovative editing techniques for the concept of time and space in Embroidered Spring Knife.


"Will there be embarrassment for the first nomination?" Lan Yu asked.


"Dare not, because the best editing award was restored for the first time in so many years, I will have a chance to nominate, which is already a historic event," Zhu Yun waved his hand. "Embroidered Spring Knife actually did something different when editing, but it seems that few people except the director agree with what we did, so that nomination is particularly important to me."


In 2019, he finally won the best editing award in the 32nd Golden Rooster Award of China for his inheritance of editing techniques of self-concept of time and space in Entering Beijing. At the highlight of his life, he deeply thanked Fu Zhengyi, a senior in the industry. "Today, this award is particularly heavy in my hand, because the predecessors of China film editing are constantly working hard. Please allow me to express my respect and gratitude to them!"


When Lan Yu asked about the significance of the Fu Lao in his mind, he said that the Fu Lao is a great god in his heart and an example in the mind of every editor in China editing industry. He also said that he was lucky when he won the prize, and these "descendants" had to thank the "predecessors" of Fu Lao for planting trees.


Add fire and material to the film.


"As a filmmaker, you have a research field of your own, which is really a very happy thing. Moreover, this matter was repeatedly recognized at the Golden Rooster Award, which gave me great encouragement. " Zhu Liyun talked excitedly about his creative mood.


Talking about his love for editing, his words are even more dense. "If you immerse yourself in it, it will look tired, lonely and hard to others, but I will feel no, I am not so tired. I think the first and most important thing in the editing industry is that you have to love movies, and you must find something different from what everyone thinks is the same. It needs to be carried out with full attention. "


During the intensive editing of the Golden Rooster Award-winning work "Into the Capital", one day, many opera experts came and said that the opera had not been finished and had to be sung from the beginning. After about an hour, Zhu Yun stood up and said, "Stop, stop, we can’t change it like this. We must ensure the film, and I will respect the opera itself to the maximum extent."


In the end, he drew lessons from many expressions of traditional operas in the editing, and showed many scenes of freeze-frame appearance. "We must do things according to the materials, first take the materials to stroke the plays, and then find ways to add fire and materials to the plays."


In the last month of Embroidered Spring Knife, he and his team, such as the chef with exquisite cooking skills, completely changed the second half of the story into a "dish", and made five large parallel clips of the whole film, completely breaking the time and space, and even mixing the scenes of day and night.


In this year’s Spring Festival movie, there are two scenes that go home during the day and go home at night. He didn’t watch them, so he cut them together — — When a poor man comes home and pushes the door and sees a mansion, a man who is used to a mansion loses his memory and pushes the door when he comes home. This reaction and contrast are the same in specific emotions.


In Lan Yu’s view, the best editing undoubtedly needs to give the director extra points. He agreed, "Right, editor, don’t try to have your own style. What you have to do is to pulse the film, then see what the director needs and try to maximize his demands."


Lan Yu pondered for a moment and asked, "So in the process of your cooperation with every director, will it be very tacit?" I believe that there should be many moments of dispute in the process of cutting. "

Zhu Liyun smiled and said, "I will argue more directly with this relationship. When filming "Embroidered Spring Knife", once we were all about to fight, and there was a scene where we were carrying our backs. Then Liu Shishi said that Zhang zhen was injured, so he helped him cover the wound. At the beginning of filming, I felt that only one shot was needed for that scene; But Lu Yang felt that both sides should be taken care of, so I insisted that it should not be interrupted by editing points in the middle. When we connect the whole film, I won’t argue with him about it anymore, because I think it needs to be interrupted in terms of the rhythm of the whole film, and its rhythm is the same. "


"Later, when I cut it, I told the old road (Yang) that today I won’t cut it first. Let’s discuss one thing first. Can this novel change reality? We discussed this for three to four hours. In fact, the final solution was that we added a voice-over to solve this problem. "


Every movie, he received hundreds of hours of material, so he began to edit it on the spot. "Into the Capital" was roughly cut out for 150 minutes, A Writer’s Odyssey was roughly cut out for 4.5 hours, and "Crowd" was roughly cut out for 5 hours and 40 minutes. He needs to cut them to a reasonable screening duration. "Because the audience will be tired after a long time, we must consider how much information the audience can accept."


Lan Yu noticed the concept of live editing. Zhu Liyun explained that his first contact with live editing was actually when the director was shooting. He was the live editing of that film and helped the director verify this sub-shot. At first, he couldn’t understand. At that time, director Tsui Hark often came over and asked him, "Did we shoot enough?" Because director Tsui Hark came from the film era, in order to save film, every shot will need to be edited.


And when the digital age comes, we don’t need to worry about a provincial material. Although his graduation homework in 2009 was still on film, it was all digitized after graduation. This has reduced the cost of many projects. He said, "I’m the only one in the editing group. Only the digital age can support us to do this. It’s because of the dividend of the digital age that there are so many materials for us to play freely, and then the editing really becomes an editing, not just an execution by the director."


For the future direction of editing, he thinks that the future films will make some breakthroughs in time and space, and take emotions and expressions as the main line to narrate. Therefore, he is also trying hard in this direction, and he also sees many people trying hard to do this kind of attempt.


The man bought a lottery ticket for one month and failed to win the prize. The police found that he bought a fake lottery ticket.

  ▲ Feng, the owner of the fake lottery shop. Compared with the real lottery (right), the fake lottery sold by Feng is obviously different. Our reporter Gan Xiayi photo

  "I may have bought a fake lottery ticket … …” Not long ago, Mr. Wu, who lives in Chen Jiaqiao, Shapingba, came to the police station to report that he had never won a lottery in a lottery shop, so he suspected that the lottery was fake.

  Is Mr. Wu "unlucky" or did he really encounter a fake lottery ticket?

  I bought lottery tickets for a month and didn’t win any small prizes.

  Mr. Wu works in Chen Jiaqiao. When he has a rest, he likes to play an online instant lottery called "Shi Shi Cai" with his friends in the lottery shop. The time lottery belongs to Keno lottery, approved by the Ministry of Finance, and issued by China Welfare Lottery Issuance Management Center in the area under the jurisdiction of Chongqing, which belongs to the regular welfare lottery.

  Mr. Wu said that he had played "Time Lottery" in other places before. Although he didn’t win the grand prize, he often won small prizes. However, he spent a month in this lottery shop in Chen Jiaqiao, invested thousands of dollars and didn’t win any prizes, which made him suspicious.

  On the 16th of this month, Mr. Wu reported the case to the Chen Jiaqiao police station. When he took out the lottery tickets bought in this lottery shop from his bag, the police soon found that these lottery tickets were very different from the regular lottery tickets sold in the market: generally speaking, the regular lottery tickets were colored, with the logo and pattern of the China Welfare Lottery on them, and a line of anti-counterfeiting codes with two-dimensional code patterns. The lottery ticket that Mr. Wu took out is no different from the cashier’s receipt in the supermarket. There is neither a sign of China Welfare Lottery nor an anti-counterfeiting code.

  Hearing this explanation from the police, Mr. Wu shouted that he was fooled. At that time, he only looked at the lottery results on the TV screen and didn’t notice the difference of lottery tickets at all.

  The fake lottery shop has been in business for three months.

  According to the police, according to national laws and regulations, issuing lottery tickets without permission has constituted the crime of illegal business operation. Chen Jiaqiao police station immediately investigated the shop where Mr. Wu bought lottery tickets, and found that in addition to this lottery shop, another lottery shop on the street also illegally sold lottery tickets.

  On the afternoon of 16th, the police seized two shops that illegally sold fake lottery tickets, seized four computers, four televisions and two bill printers for illegally selling lottery tickets, and brought the owners Feng Mou, cashiers Liu Mou, Wan Mou and dozens of people who bought lottery tickets on the spot back to the police station for investigation.

  After inquiry, Feng confessed the criminal fact that he had opened a fake "time color" in Chenjiaqiao Town since November 2016 without the approval of the state.

  The police said that there were no signs hanging outside the two fake lottery shops. However, the setting in the store is almost exactly the same as that in a regular lottery shop, so the customers who come here are not aware of the abnormality.

  Whoever the boss wants to win the prize will win.

  Feng confessed that he had seen such a fake lottery shop in other places before, and thought it was quite profitable, so he bought the system developed by the other party and opened two stores in Chenjiaqiao Town after he came back. The interface of the lottery ticket is almost the same as that of the China Welfare Lottery, and the lottery ticket is awarded every 10 minutes, but there is no sign of the China Welfare Lottery, and the lottery ticket is also printed on ordinary cashier receipt paper. Despite this, many people didn’t notice these details and came to his shop to buy lottery tickets.

  Feng said that the lottery system is controlled by himself. Whoever wants to win the prize can win the prize, and whoever doesn’t want to win the prize doesn’t have a penny. In just a few months, Feng illegally sold lottery tickets for more than 300,000 yuan and made a profit of nearly 100,000 yuan.

  The two female cashiers confessed that they were hired by Feng. Although they knew that this was illegal, they were not very clear about the "mystery" because they had never bought a lottery ticket. They usually collected money according to the boss’s requirements. According to them, dozens of people come to the store to buy lottery tickets every day, all of whom are local residents or migrant workers.

  The police investigating the case said that the amount of fake lottery tickets sold by Feng ranged from 5 yuan to 100 yuan. They have sold thousands of fake lottery tickets in the past three months. At present, the criminal suspect Feng was released on bail pending trial on suspicion of illegal business operation, and the case is still being further processed.

  The police reminded that when buying lottery tickets, you must keep your eyes open, go to the regular sales point of China Welfare Lottery, and pay attention to whether the lottery tickets have the words and anti-counterfeiting codes of China Welfare Lottery, so as not to be deceived. If you find the sales point of fake lottery tickets, please call 110 in time, and the police will crack down on such illegal and criminal acts. Our reporter Tan Yao

Stock dynamics of Haidilao on January 25th: recorded an increase of 2.57%, maintaining a volatile upward trend.

As of the close of January 25th, the share price of Haidilao (HK: 06862) closed at HK$ 13.56, with the lowest point of HK$ 12.96 and the highest point of HK$ 13.58. Hong Kong stocks generally rose, and the Hang Seng Index closed at 16,211.96.

According to Zhang Ying, general manager of Haidilao Community Operation Division, at present, Haidilao delivery has formed a business matrix including "Haidilao Happy Banquet", "Haidilao Hot Pot Delivery" and "Haidilao Hot Pot Dishes". Haidilao’s innovation in delivery business has changed the delivery of catering from a simple "product delivery" to a comprehensive experience of "product+service+scene delivery".

Haidilao brand was founded in 1994. After nearly 30 years of development, Haidilao International Holdings Co., Ltd. has grown into an internationally renowned catering enterprise. As of June 30, 2023, the total number of restaurants in Haidilao was 1382.

Haidilao has been tested by the market and customers for many years, and has successfully built a high-quality hot pot brand with high credibility and integrating the characteristics of hot pots from all over the world. As a large-scale chain catering enterprise whose business involves the whole world, Haidilao adheres to the concept of honest management, and takes improving the stability and safety of food quality as the prerequisite to provide consumers with more intimate services, healthier, safer, more nutritious and more assured food.

Disclaimer: The content of this article reprints enterprise information for this website, which only represents the author’s personal views and has nothing to do with this website. The contents involved do not constitute investment and consumption suggestions, and are for readers’ reference only. Please check the relevant contents yourself.

Original text transferred from: Xianning News Network
Reporting/feedback

Lishui, Nanjing: Women’s Football Team’s Dream Pursuit

Rugby is a competitive sport, attracting more and more attention. In Lishui District, there is a women’s football team run by the municipal team. They are all young players under the age of 20. After hard training, they have achieved good results and delivered many excellent athletes for the national youth team and the provincial team.
After the Mid-Autumn Festival, the reporter met the members of Group B of Lishui Women’s Football Team who were conducting daily training at the track and field of Lishui Sports Park. In the women’s rugby final of the 20th provincial sports meeting, which just ended not long ago, they beat their opponents with an absolute advantage of 33:5 and won five gold medals for Nanjing. At present, the girls are preparing for a provincial professional selection at the end of September, and the outstanding players will have the opportunity to enter the provincial team. "After the contest, everyone needs to take a break for physical and psychological adjustment. Although the current state has not reached the best, the basic physical fitness, speed and strength are slowly recovering." Li Yuanyuan, coach of Lishui Women’s Football Team, told reporters that there are 10 players in Group B, 8 of whom are Lishui people, born in 2006-2007. Because our country has not developed rugby for a long time, most of the girls are "half-way monks". All along, everyone has been studying and training in the track and field of Lishui District Sports Park, rain or shine.
Rugby is an all-round antagonistic sport, which requires athletes to have the qualities of speed, physical fitness, strength and will, as well as the skills of falling to the ground and self-protection. On the field, it is a big challenge for these teenage girls to fight and collide for a ball. Team members Chen Yan and Li Chen are twin sisters from Honglan Street. They began to practice track and field at the age of 10, and both entered the football team through selection at the age of 12. For four years, the two sisters fought side by side and worked together for honor. "I often get injured in the process of training, and there may be secondary injuries in the process of rehabilitation, which will bring me a strong frustration. After each injury, the coach will take the initiative to find me, guide me and help me adjust my mentality. " Chen Yan said that injuries to football players are commonplace, and at first the sisters’ choices were not understood and supported by their parents. "Because after we practiced, we found that we liked this project very much, so we persisted. Plus, we made achievements later, and our parents supported us." Li Chen said frankly that although she was tired from training, her life was very full and happy with her sister and other teammates.
The dazzling achievements are inseparable from the accumulated sweat. No matter whether it is windy or rainy or the sun is shining, the training has never stopped. It is precisely because the coach and the team members are United as one, and with their persistent persistence and strong strength, they handed in a bright report card at this provincial sports meeting. "We also hope that through their efforts, more people will pay attention to the sport of rugby." Li Yuanyuan said.
Rong media reporter Yan Xingyu
Reporting/feedback