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)

Don’t get me wrong about these English (8)

Eminem, an American rapper, brought the film to perfection in the last part of his semi-autobiographical film "Eight Miles". Jimmy, who he played, won the championship in the impromptu rap contest in Detroit’s black area. When all the rappers waved their arms up and down with the music, you might feel excited. Many rappers saw this part and strengthened their belief in making Chinese rap music, but this English that made the audience high was easily misunderstood as other meanings.

1. bring down the house.

Get a house full of applause, not knock down the house.

Don't get me wrong about these English (8)

2. have a fit.

Lose one’s temper, fly into a rage, not trying on clothes

Don't get me wrong about these English (8)

3. make one’s hair stand on end.

It’s creepy, not outrageous.

Don't get me wrong about these English (8)

4. be taken in.

Deceived, not accepted.

Don't get me wrong about these English (8)

5. pull up one’s socks.

Courage, not socks.

Don't get me wrong about these English (8)

In a blink of an eye, 2013 is over half. How is your dream coming true? Courage to pursue your dream can be not only someone else’s business, but also your business. I also wish you pull up your socks and chase your dream. See you next week!

Related reading

Don’t get me wrong about these English (7)

Don’t get me wrong about these English (6)

Don’t get me wrong about these English (5)

Don’t get me wrong about these English (4)

Don’t get me wrong about these English (3)

Don’t get me wrong about these English (2)

Don’t get me wrong about these English meanings (1)

About the author:

Don't get me wrong about these English (8)

Leon, graduated from Harbin Institute of Technology, is a bilingual psychotherapist. Former editor-in-chief, good at American English, friends ashes powder, hobby HipHop and raising dogs. Now I live in Beijing and have my own psychological studio.

(Editor of China Daily English Dianjin Julie)

China’s economic development is full of stamina and keeps moving forward.

       CCTV News:Today (October 27th), News NetworkBroadcast a reportA number of data in China’s economic field have been published. Key words such as "growth" and "high level" have highlighted the overall development trend of China’s economy, and at the same time, other fields have also frequently achieved good results. The "big ship" of China’s economy will surely ride the wind and waves and continue to move forward.

In the third quarter, the profits of industrial enterprises nationwide increased by 7.7% year-on-year.

According to the data released by the National Bureau of Statistics today (October 27th), since the beginning of this year, with the continuous improvement of market demand and the steady growth of industrial production, the revenue and profits of industrial enterprises have continued to improve. Among them, the profits of industrial enterprises above designated size increased by 7.7% year-on-year in the third quarter, and the profits of industrial enterprises showed an accelerated recovery trend. On a monthly basis, in September, the profits of industrial enterprises above designated size increased by 11.9% year-on-year, achieving double-digit growth for two consecutive months.

The revenue of industrial enterprises has obviously improved. In the first three quarters, the operating income of industrial enterprises above designated size nationwide reached 96.35 trillion yuan, which was the same as that of the same period last year, and the growth rate was faster than that of the first half and the first quarter.

       In the third quarter, the profit of manufacturing industry increased by 11.8% year-on-year, of which the profit of raw material manufacturing industry increased by 60.8% year-on-year and the profit of consumer goods manufacturing industry increased by 11.8% year-on-year.

In the first three quarters, the investment scale of transportation fixed assets remained high.

According to the latest data released by the Ministry of Transport, in the first three quarters, China’s transportation fixed assets investment reached 2,877.5 billion yuan, a year-on-year increase of 5.6%, and the scale of transportation fixed assets investment remained high. Port cargo throughput also maintained rapid growth in the first three quarters. 1— In September, the total cargo throughput of ports nationwide was 12.54 billion tons, up 8.5% year-on-year, of which the foreign trade cargo throughput was 3.77 billion tons, up 10.1% year-on-year. Container throughput reached 230 million TEUs, up 5.2% year-on-year.

Data sorting out the achievements of the 134th Canton Fair.

The second phase of the 134th Canton Fair ended today (October 27th). Up to now, this year’s Canton Fair has carried out 53 "Bridge of Trade" global trade docking activities, attracting more than 220 buyers and more than 620 suppliers for "one-on-one" docking negotiations, with an intended purchase amount of about 100 million US dollars. Since the opening ceremony, more than 157,000 overseas buyers from 215 countries and regions have attended the meeting, an increase of 53.6% over the same period last year. Among them, there are more than 100,000 buyers in the "Belt and Road" countries, accounting for about 64%.

The third phase of the Canton Fair will be held from October 31st to November 4th, with more than 11,000 enterprises participating offline. The exhibition is divided into five sections: toys and pregnant babies, fashion, household textiles, stationery and health and leisure.

In October in Yangcheng, all merchants gather. In Guangzhou these days, not only is the booth crowded, but many hotels in the city are also hard to find a room. Against the background of sluggish demand in the world economy, such a scene is very emotional. The bustling passenger flow is people’s confidence in China’s economy.

The 24th Central China Agricultural Expo opened.

       The 24th Central China Agricultural Expo opened today in Changsha, Hunan. This year’s Expo set up special exhibition halls such as the Central Inter-provincial Pavilion and the Agricultural Service Pavilion, which attracted nearly 5,000 enterprises to focus on the exhibition and sale of high-quality agricultural products. During the exhibition, China Central Agricultural Brand Promotion Conference and other activities will be held.

The latest scientific and technological achievements of start-up technology enterprises are concentrated in appearance.

Recently, the 17th Innovation China was held in Beijing Shougang Park. Nearly 100 outstanding start-up technology enterprises from all over the country brought their latest scientific and technological achievements to the show. Focusing on the theme of artificial intelligence, this activity covers intelligent manufacturing, life sciences, new energy and green economy, intelligent interconnection and new businesses. Since the launch of the activity in 2006, more than 1000 investors have been gathered to connect with entrepreneurs on the spot to help the entrepreneurial team grow rapidly.

In the third quarter, civil aviation completed 180 million passenger trips.

In the third quarter, China’s civil aviation maintained a safe and orderly recovery trend, and transportation production continued to improve. The total transportation turnover of the whole industry was 33.68 billion tons kilometers, an increase of 89.3% year-on-year; There is a strong demand in the passenger transport market. The whole industry has completed a total of 180 million passenger trips, up 108.3% year-on-year, and the passenger transport scale of the industry has reached a quarterly record high.

This year, China’s digital supply chain market will exceed 32 trillion.

The relevant person in charge of China Federation of Logistics and Purchasing introduced at the 6th Digital Supply Chain Platform Development Conference today (October 27th) that China’s economy is recovering continuously and its growth momentum has been enhanced. Under the background of accelerating the reconstruction of the global industrial chain supply chain, the development of China’s digital supply chain platform has entered the fast lane.

According to the relevant person in charge of China Federation of Logistics and Purchasing, it is estimated that as the largest manufacturing and consumer market in the world, the market size of China’s digital supply chain will increase from 8.25 trillion yuan in 2018 to 27.2 trillion yuan in 2022, with a compound annual growth rate of 26.94%. In 2023, the market size of digital supply chain will exceed 32 trillion yuan. The security and stability of the supply chain provides strong support for smooth double circulation, promoting high-quality economic development and enhancing international competitiveness.

China has boosted the global mining market to stabilize and recover.

The Global Mining Development Report 2023 shows that China’s economy has recovered rapidly, and the demand for mineral resources has remained high, effectively stimulating the global consumption demand for energy resources.

       According to the latest data, in 2022, with the global demand for mineral resources shrinking, China’s energy and mineral resources remained stable and its consumption continued to grow, which played an important role in stabilizing the global mining market. For example, in 2022, China’s coal consumption reached 3.041 billion tons, a year-on-year increase of 4.3%. The domestic coal production capacity was released steadily, and the coal mine operating rate remained high, with the annual output reaching 4.496 billion tons, up 9% year-on-year.

In the first three quarters, residents spent a total of 3.69 trillion yuan on domestic trips.

       The Ministry of Culture and Tourism released the data of domestic tourism in the first three quarters of 2023 today (October 27). According to the statistical results of domestic tourism sampling survey, the total number of domestic tourists in the first three quarters of this year was 3.674 billion, an increase of 1.58 billion over the same period of last year and a year-on-year increase of 75.5%. In the first three quarters, residents spent 3.69 trillion yuan on domestic trips, an increase of 1.97 trillion yuan or 114.4% over the previous year.

Ministry of Commerce: I am confident to achieve the goal of promoting stability and improving quality of foreign trade throughout the year.

On October 26th, the Ministry of Commerce held a regular press conference. The spokesman said that China’s foreign trade is running smoothly on the whole, and it is confident to achieve the goal of promoting stability and improving quality of foreign trade throughout the year.

The Ministry of Commerce said that since the beginning of this year, due to high inflation, high inventory and geopolitical risks, global trade has continued to be weak. According to the data of the World Trade Organization (WTO), global exports fell by 4.6% in the first half of the year. Based on concerns about growth difficulties and challenges, the WTO recently lowered the growth rate of global merchandise trade in 2023 from the previous forecast of 1.7% to 0.8%.

In the face of multiple risk challenges, China has solidly promoted the policy of stabilizing foreign trade, and China’s foreign trade has generally operated smoothly, especially in recent months.

Shu Yuting, spokesperson of the Ministry of Commerce:In terms of scale, China’s import and export scale rose quarter by quarter, and increased month by month in the third quarter. In September, the import and export volume reached a single-month high in the year. In terms of share, WTO data show that China’s export international market share reached 14.2% in the first half of the year, 0.4 percentage points higher than the same period last year.

From the main point of view, the number of foreign trade enterprises with import and export performance in the first three quarters was 597 thousand, which was close to the level of last year. From the perspective of kinetic energy, superior products such as automobiles, ships, lithium batteries and luggage maintained a relatively high growth rate, and new cross-border e-commerce formats continued to contribute to the increase.

Shu Yuting, spokesperson of the Ministry of Commerce:These positive changes are inseparable from the persistence and innovation of the majority of foreign trade subjects, the effective implementation of stable foreign trade policies, and the resilience and vitality of China’s foreign trade. With the continuous accumulation of positive factors, we are confident that we will continue to consolidate the good operation situation in the fourth quarter and we are confident that we will achieve the goal of promoting stability and improving quality of foreign trade throughout the year.

In addition, recently, the National Data Bureau was established. The newly established National Data Bureau is responsible for coordinating and promoting the construction of data infrastructure, coordinating the integration, sharing, development and utilization of data resources, and coordinating the planning and construction of digital China, digital economy and digital society. 

Sharp l sales plummeted, abnormal sound, gearbox frustration, car machine not updated into pain points

L Hybrid Since then, with the blessing of a new hybrid system,Changed consumers’ inherent impression of American fare oil.Coupled with the appearance of the atmosphere and good control, it has won the support of many consumers. However, with the passage of time, many car owners reported the existence of the car.qualityproblem

Recently, a Mr. Chen from Haikou, Hainan, told the Chief of Staff about the car feedback:

In April 2024, I bought a Ford Sharp L. Soon after I picked up the car, I found that when the vehicle was in the starting state, when it was at low speed or when it was accelerating or decelerating, it would send out ".Cough cough "The voice.

in additionA Mr. Li from alsoTo the chief of staffTalking about car feedback

In addition to abnormal sound, lThe gearbox still has a setback problem.The driving experience is a bit poor.

Going to the 4S shop for inspection, the after-sales staff explained: "This voicenormal, yesGear-driven",and said that the test drive also has this voice.

Faced with the helplessness of the 4S shop, the above two car owners were very confused and anxious, questioning why a car manufacturer could not repair the car?

I often listen to this questionThe chief of staff said that all riders on the car show know that the main reason is thatLack of experience in the field of mixingIt is difficult to cope with all kinds of complicated problems in actual use.

But cars, as a mass consumer product,And gearbox, as one of its core components, the problem of failure can not be ignored. WeHope Chang ‘an FordActively communicate with users to find solutions.Otherwise, it will reduce users’ trust in the brand.

Besides the gearbox problem,The car has not been updated for a long time and the navigation version is old.It is also the hardest hit area for vehicle complaints.

Many old car owners reported:

The locomotive system has not been updated for two or three years., there is a phenomenon of caton;The navigation version is old.Many routes are not accurately navigated; When buying a carOfficial propaganda can be connected to mobile phones, but as of today, this function is still not supported.



There are also some sharp car owners who have feedback:The front and rear doors are uneven, the chassis/exhaust pipe is rusted, the car crashes/black screen, and the engine lights up.











The above complaints from car owners have undoubtedly had a certain impact on the sales of Sharp L.

It is understood that from January to May 2024, the cumulative sales volume of Sharp L was 9,768 vehicles.It decreased by 61.7% year on year.. (This is just a microcosm of Changan Ford’s models. )

after allNowadays, consumers are more rational in buying cars and pay more attention to the quality and reliability of vehicles..

When a brand has frequent quality problems, it will definitely flinch and choose other brands with more quality assurance. Even former loyal fans may turn to other competitors because of their concerns about quality.


Therefore, if Changan Ford wants to get rid of the current predicament and regain the market share and the trust of consumers, it must face up to the quality problems and improve the quality control and after-sales maintenance level of its models. Only in this way can we achieve a counterattack in the fierce market competition and return to the track of sales growth.

Today’s topic:After reading this article, will you still buy Ford Sharp L?Please leave a message in the comments section.

Reading: Where is the application entrance of Huawei HarmonyOS system? Introduction to the application entrance of Huawei HarmonyOS system [Detailed explanation] Where is the application entrance of H

  As we all know, except for Apple’s ios system, other brands of mobile phone operating systems are developed and changed based on Android system. Recently, however, Huawei finally pushed the HarmonyOS System 2.0 beta version developed by Huawei. Friends who want to test can apply for developers for free and participate in the test. Let’s take a look at the specific methods below.

  1. First, click "Huawei" on Huawei’s mobile phone to enter the application.

  2. Then click "Upgrade early adopters"

  3. Find and click "Try it now", as shown in the figure.

  4. Find the model of your mobile phone and click "Register for public beta".

  5. After agreeing to a series of agreements, you can download the description file.

  6. After downloading the description file, enter "System and Update" in the phone settings.

  7. Enter "Software Update" to download and update the HarmonyOS system.

  8. At present, the models that can be updated are: Huawei Mate 40 series, Mate 30 series, P40 series, Mate X2 and MatePad Pro.

  1. If our mobile phone has not been added to the latest test list, we can participate in the beta test. After registering as a developer, you can sign up for the test on the website. [Huawei HarmonyOS Test]

  2. We can pay attention to WeChat official account, the developer of HarmonyOS.

  3. Then click "B eta beta" below.

  4. You can register to become a developer for free.

  6. At present, the test models that can participate are: Huawei P40, P40 Pro, Mate 30, Mate 30 Pro, MatePad Pro, and there is no latest Mate 40 series.

  1. How to upgrade HarmonyOS 2.0 to 3.0?

  Click on the phone settings, then enter the software update, find the corresponding page, click on the update, download, upgrade and install.

  2, HarmonyOS charging prompt tone setting tutorial

  Open the Smart Assistant and select the charging tone, and then you can set and operate it in this page.

Putin: This weapon makes the enemy "think twice before you act"

  The reference news network reported on September 6. According to the US Newsweek website reported on September 2, after Russia said that it had put an advanced intercontinental ballistic missile (ICBM) into military service, Russia stepped up its nuclear rhetoric. Putin once said that this missile will make Moscow’s enemies "think twice before you act."

  According to the official Russian news agency Tass, Yuri borisov, head of the Russian National Aerospace Group, said that the "sarmat" intercontinental ballistic missile had "taken up the combat mission".

  What is "sarmat" intercontinental ballistic missile?

  RS-28 sarmat is a liquid-fueled intercontinental ballistic missile produced by Russian Makeyev Rocket Design Bureau.

  This missile was originally designed to replace the R-36 intercontinental ballistic missile with a range of 9940 miles (1 mile is about 1.6 kilometers). NATO calls R-36 Satan, so its successor model is usually informally called Satan 2.

  The RS-28 sarmat missile is 116 feet long and weighs 220 tons. It is said that it can carry up to 15 light nuclear warheads. This missile has a range of 11,000 miles and can strike targets in the United States and Europe.

  In contrast, the American LGM-30 Militia intercontinental ballistic missile weighs about 36 tons, has a range of about 8,100 miles and a diameter of 5.5 feet (about 4 feet smaller than that of sarmat).

  Sarmat is a missile based on silo. It is believed that its initial launch stage is very short, which means that the monitoring system has little time to track its launch.

  On April 20, 2022, Russia test-fired this missile from Plesetsk, Arkhangelsk region, 500 miles north of Moscow. It is reported that the missile hit the target on the kamchatka peninsula, which is 3,700 miles away from the Russian Far East.

  As a part of the "next generation" nuclear missile technology, the "sarmat" intercontinental ballistic missile is one of six new Russian strategic weapons announced by Putin in his State of the Union address on March 1, 2018.

  After the first successful test launch in April 2022 (the United States has been informed of the test launch in advance), Putin said that the missile has "the highest tactical and technical characteristics and can overcome all modern anti-missile defense means."

  He said that the missile is unique in the world and "there will be no similar weapons for a long time to come". Putin also said that this weapon will make those who try to threaten Russia "think twice before you act."

  On the Russian -1 Channel’s "60 Minutes" program, Alexei Zhuravlev, chairman of the nationalist party Motherland Party, said that as long as there is a "sarmat" missile, "the British Isles will cease to exist".

  However, Pavel Podvig, who is in charge of the research project of "Russian Nuclear Forces" in Geneva, wrote on the X website (the former Twitter website) that in February this year, Russia’s second test-fired "sarmat" intercontinental ballistic missile failed due to a secondary fault. He wrote: "Besides, people have other questions. So before it was confirmed, we returned to a state of success, failure and no deployment. " (Compile/Yang Xuelei)

Mobile phone follow-up, mobile phone prescription … Internet medical treatment makes it easier to see a doctor.

  Since 2020, in the process of fighting the COVID-19 epidemic, public hospitals all over the country have launched Internet medical services, which has effectively improved patients’ medical experience.

  According to the data released by National Health Commission, at present, there are more than 1,100 Internet hospitals in China, and 7,700 hospitals above the second level provide online services. The online appointment rate of tertiary hospitals has reached more than 50%, and 3,300 hospitals will make appointments by time to 30 minutes. More than 90% of tertiary public hospitals have realized the sharing of hospital information. The telemedicine collaboration network covers more than 24,000 medical institutions in all prefecture-level cities. 30 provinces have established Internet medical service supervision platforms.

  Mobile phone follow-up, simple and quick operation.

  On-line follow-up saves time and money for patients and their families, saves patients from the pain of travel and fatigue, and is conducive to postoperative rehabilitation.

  "Director Chen, I have a cough. What’s the matter?"

  "When the nutrition tube is placed in the throat, it will be irritating, and it is normal to cough occasionally."

  "It’s been a month since the operation. Can I unplug the tube and eat by myself?"

  "The nutrition tube is yours ‘ Lifeline ’ If you pull it out, there will be obstacles to eating directly. The intubation is really uncomfortable, but I hope you can bear it again … …”

  This is Chen Keneng, director of the Department of Thoracic Surgery, Peking University Cancer Hospital, who is giving a follow-up visit to Ms. Li who is far away from home in Xiamen, Fujian Province through the Internet.

  At the end of January this year, Ms. Li had esophageal cancer resection in Peking University Cancer Hospital, and returned home to recuperate after discharge. Earlier, Ms. Li had bought a plane ticket to Beijing and was going to Beijing for a follow-up visit. My friend said that she could make a follow-up visit online. She felt very fresh and wanted to try it, so she returned her ticket. With the help of her son, Ms. Li made an appointment with Chen Keneng’s follow-up number by using the mobile phone software of "North Swelling Cloud Medical Records" and successfully completed the follow-up visit. "It’s so convenient to return to the mobile phone!" Ms. Li told reporters through video.

  How to operate the mobile phone follow-up visit? The staff of Peking University Cancer Hospital opened the "North Swelling Cloud Medical Record" to demonstrate to the reporter: On the day of the visit, the patient can log in to the "North Swelling Cloud Medical Record" 30 minutes in advance, click "Online Follow-up" on the homepage, and enter the "online consultation room" to wait for treatment. After that, the doctor will take the initiative to invite the consultation, and the patient can start the consultation by clicking "Answer". The whole process is easy to operate, even for elderly patients who can’t surf the Internet, they can easily complete it with the help of their families.

  In April 2020, Peking University Cancer Hospital was granted the qualification of Internet diagnosis and treatment. Up to now, the cumulative number of online follow-up visits has exceeded 40,000, of which 22.8% have been followed up more than three times. Chen Keneng said that the patients in Peking University Cancer Hospital come from all over the country. After the initial diagnosis and operation, patients need to return to the clinic, even for many times. If you have to travel long distances to Beijing for each follow-up visit, some of them need to be accompanied by their families, which will cost a lot. Many follow-up visits don’t have to go to the scene, and they can also be solved through video. Network follow-up saves time and money for patients and their families, saves patients from the pain of traveling by boat and is conducive to postoperative rehabilitation.

  Zhao Chengsong, assistant to the president of Beijing Children’s Hospital affiliated to Capital Medical University and director of the outpatient department, said that Beijing Children’s Hospital recognized the results of the mutual recognition program for children in local hospitals of the same level or Beijing, Tianjin and Hebei. After the child has finished the examination in the local hospital, the film or examination report will be uploaded to the Internet medical platform of Beijing Children’s Hospital, which can also be seen by the attending doctor.

  "Ensuring the quality of medical care is the life of Internet medical care." Zhao Chengsong said that for large public hospitals, it is an inevitable trend to carry out Internet diagnosis and treatment. In order to ensure the quality of medical care, doctors should be trained on the Internet to improve their online diagnosis and communication skills. "Internet medical care is not exclusive to young doctors. Experienced experts should take the lead in embracing the Internet so that more patients can enjoy quality medical resources."

  Heng Fanxiu, director of the Information Department of Peking University Cancer Hospital, believes that the smooth progress of Internet diagnosis and treatment in large hospitals is inseparable from an efficient information management system. The Internet diagnosis and treatment system of Peking University Cancer Hospital has been updated for 38 times since it was launched. Each version update is to fix loopholes and improve the efficiency and security of the system. "The hospital’s Internet medical data should be encrypted and stored on an independent server to ensure the safety of patient medical data." Heng anti-repair theory.

  Prescribe drugs online and deliver them home by express delivery.

  Doctors need to use electronic signature when prescribing drugs online, and pharmacists sign after passing the internal system of the hospital to ensure that the prescription is reasonable, legal and compliant.

  "The medicine prescribed online in the morning arrived home by express delivery before dark, so fast!" Mr. Zhang, who lives in Tianjin, took his 8-year-old daughter with precocious puberty and used her mobile phone to use the WeChat applet — — A follow-up visit was made on the "Beijing Children’s Hospital Service Number". Doctors make prescriptions online after video consultation. After a few minutes, the pharmacist approved it.

  After seeing a doctor, Mr. Zhang clicks on the button of "online drug purchase", selects the prescription to be paid, clicks on "immediate payment and delivery", selects the service of "express delivery to home" in "delivery mode", fills in the address, telephone number and other information and pays, and then completes the drug purchase process. "Simple operation and fast payment. It is also very easy to buy medicine online! " Mr. Zhang said.

  In April 2020, Beijing Children’s Hospital opened Internet diagnosis and treatment service, and patients can enjoy online follow-up, online prescription and prescription drug delivery service through their mobile phones. At present, the vast majority of departments in Beijing Children’s Hospital have carried out Internet diagnosis and treatment, and the hospital is equipped with corresponding equipment to facilitate doctors to go out to the Internet clinic.

  How to ensure the safety of doctors prescribing drugs online? Zhao Chengsong introduced that Beijing Children’s Hospital has established a relatively complete Internet management system and implemented an electronic signature system and a drug pre-audit system. Doctors need to use electronic signature to prescribe drugs online, and pharmacists should sign after passing the internal system of the hospital to ensure that the prescription is reasonable, legal and compliant.

  How to send the medicine to the patient’s home safely and quickly after the prescription is made? Zhao Chengsong said that Beijing Children’s Hospital cooperated with China Resources Pharmaceutical Group to develop a prescription circulation platform. On the platform, the hospital is responsible for reviewing the prescription and then pushing it to China Resources Medicine. China Resources Medicine will arrange the nearest pharmacy according to the patient’s location, use professional medical logistics to send drugs and deliver them to the patient’s home in time.

  In September, 2020, Peking Union Medical College Hospital’s Internet medicine distribution service was officially launched. In order to make the express delivery arrive more accurately, the hospital selects high-quality drug delivery contractors and signs long-term cooperation agreements. National non-medical insurance patients can enjoy the "peer-to-peer" delivery service of drugs to their homes after returning to Peking Union Medical College Hospital online, and can inquire about prescriptions and medication guidance on the mobile phone client of Peking Union Medical College Hospital. If in doubt, they can also consult with Concord pharmacists online.

  Some Chinese medicine hospitals are also exploring online express delivery services for Chinese herbal medicine prescriptions. In April 2020, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine issued the first online prescription of Chinese herbal medicine in Shanghai. This prescription was delivered to patients’ homes in Yancheng City, Jiangsu Province free of charge within two days through the distribution system of traditional Chinese medicine decoction pieces in the hospital. Previously, Longhua Hospital has built a relatively mature distribution system for Chinese herbal pieces. The relevant person in charge of Longhua Hospital said that it will continue the free drug delivery measures in Jiangsu, Zhejiang, Shanghai and Anhui to provide more convenience for patients.

  "At present, the hospital’s Internet diagnosis and treatment platform needs to be continuously improved. For example, the types of drugs in some hospitals’ Internet diagnosis and treatment platforms are not complete enough to issue laboratory tests and checklists." Zhao Chengsong suggested that in order to better serve patients, hospitals and drug distribution enterprises should strengthen cooperation, optimize the Internet diagnosis and treatment platform, provide more quality services, and further enhance patients’ sense of medical treatment.

  Online payment, real-time settlement of medical insurance

  "internet plus" medical services are included in medical insurance payment, and online and offline medical services are treated fairly.

  Aunt Jing, who lives in Jinan City, Shandong Province, is 69 years old and suffers from high blood pressure. She usually needs to go back to the clinic regularly to get medicine. She completed the medical insurance identity verification and medical insurance binding on the "Shandong Medical Insurance Great Health" WeChat official account, and chose the Internet hospital for treatment, so she could use medical insurance to pay. "Mobile phone WeChat pays fees, medical insurance is settled in real time, and the operation is not complicated." Aunt Jing said.

  In order to facilitate patients with chronic diseases to seek medical treatment, Shandong Province has established a Shandong medical insurance platform, relying on Internet hospitals to open online payment for medical insurance for Internet hospitals stationed in the platform, and medical insurance information can be verified immediately. At present, a comprehensive medical security service system of "internet plus Medical Insurance+Medical Care+Medicine" has been established in Shandong Province, which realizes the seamless connection of key links such as medical insurance certification, follow-up check-up, online prescription and delivery of medicines to home. Insured people in Shandong province can get one-stop convenient services such as online follow-up, prescription and online payment of medical insurance through mobile phones without leaving home.

  For some elderly people, the mobile phone operation is not smooth, and the Shandong Medical Insurance Platform has also opened a manual customer service hotline to help patients with chronic diseases complete the first signing and follow-up service. Uncle Lin, who has been bedridden with hemiplegia for more than 20 years, used this service. Uncle Lin and his old couple only have an old man-machine machine. Uncle Lin’s daughter signed the platform for him for the first time with a smart phone and saved the hotline on the old man’s mobile phone. In the future, the elderly only need to make a phone call and wait for the medicine to be delivered at home. The medical insurance is settled online in real time, and the self-paid part is collected by the delivery staff.

  In March, 2020, in order to meet the drug demand of patients with chronic diseases during the epidemic prevention and control in COVID-19, the National Medical Insurance Bureau and the National Health and Health Commission issued the Guiding Opinions on Promoting the "internet plus" medical insurance service during the epidemic prevention and control in COVID-19, clarifying that qualified Internet medical institutions provide the insured with online follow-up services for common diseases and chronic diseases, and make online electronic prescriptions and offline prescriptions, so that the insured can enjoy the medical insurance payment treatment as if they were in a physical hospital. "internet plus" medical insurance service was welcomed by patients shortly after its opening. Taking Shanghai as an example, as of June 2020, 12 medical institutions have realized online real-time settlement of medical insurance, with more than 17,800 settlement times and a total cost of 2,598,200 yuan.

  In October, 2020, the National Medical Insurance Bureau issued the Guiding Opinions on Actively Promoting the Medical Insurance Payment for internet plus Medical Services, which clarified the consultation fees and drug fees incurred by patients with chronic diseases and special diseases for online follow-up, and prioritized them into the scope of medical insurance reimbursement, supported the circulation of prescriptions for medical follow-up visits in internet plus, and explored the interconnection of prescription information purchased by designated medical institutions with designated retail pharmacies.

  Lu Qingjun, director of the office of National Health Commission Telemedicine Management and Training Center of China-Japan Friendship Hospital, said that the "internet plus" medical insurance payment policy made it clear that the "internet plus" medical service should be included in the specific content of medical insurance payment, and the online and offline medical services should be treated fairly, and priority should be given to ensuring the demand for follow-up visits for chronic diseases and special diseases in outpatient clinics, and supporting the circulation of purchased prescriptions, which not only facilitated patients, but also reduced the pressure on hospitals. Internet medical care has broken the time and space restrictions for patients to seek medical treatment, which has made it easy for many patients to seek medical treatment across provinces and different places, helped to promote the homogenization of medical resources, and enabled patients in remote areas to enjoy high-quality medical resources conveniently and better meet the people’s medical and health needs. (photo by Shen Shaotie)

Jinzhong, Shanxi: Two "silly roe deer" were trapped in the county town at night for two days.

Jinzhong, Zhongxin. com, July 16 (Lu Qiguo, Jin Fengren Jie) One roe deer was stuck in the gap of the gate railing, and the other roe deer fell under the river dam. On July 15th and 16th, Zhangzi was trapped in Zuoquan County and Xiyang County, Jinzhong, Shanxi, respectively. The local fire rescue department rescued Zhangzi and handed it over to the forestry department.

At 7 o’clock on the 15th, Zuoquan County Fire Rescue Brigade received an alarm: a roe deer was stuck in the gap of the gate railing of a waste collection station at the back door of Taihang apartment in the county. When the firemen arrived at the scene, the roe deer struggled violently because of excessive shock, causing its right hind leg to break and its bone to be exposed.

Firefighters cooperate with animal protection personnel of forestry department to perform amputation operation on the injured roe deer. Lu yuguo

In order to rescue the roe deer as soon as possible, firefighters used hydraulic expansion tools to expand the gate railing, rescued the trapped roe deer and brought it back to Zuoquan County Fire Rescue Brigade. Subsequently, the animal protection staff of Zuoquan County Forestry Bureau rushed to Zuoquan County Fire Rescue Brigade to perform "amputation" on the injured roe deer. Unfortunately, this roe deer died because it was stuck for a long time and was seriously injured.

At 6 o’clock on the 16th, Xiyang County Fire Rescue Brigade received an alarm: a roe deer fell under the dam in the urban section of Xiyang County of Songxi River and hid on the side of the rubber dam because of fright.

The Xiyang County Fire Rescue Brigade first sent five firefighters down to the bottom of the dam, tied the trapped roe deer with ropes, and then fixed the roe deer with a multifunctional rescue stretcher and lifted it to the ground.

After on-site inspection, there is no wound on this roe deer. More than an hour later, the firemen handed over the roe deer to the forestry police station and took it to the wild for release.

Firefighters rescued the roe deer trapped under the river dam. Ren Yushe

In recent years, with the continuous improvement of the ecological environment and the strengthening of wildlife protection, many places in Jinzhong City have been trapped in the county town of Zhangzi at night. On May 28th last year, a roe deer was trapped in the fence at the entrance of the government affairs hall of heshun county City at night, and was rescued and released by the local fire rescue department.

The fire department reminds that although the roe deer is nicknamed "silly roe deer" because of its stupidity, it belongs to the "three-owned" protected animals, and illegal hunting, trading and eating are strictly prohibited. If you find that the roe deer is trapped, please call 119 in time, and the fire rescue department will rescue the roe deer and notify the local forestry department to handle it properly. (End)

It turns out that seals are so interesting that they have increased their knowledge!

When it comes to seals, I believe everyone will be familiar with them. Like walruses, they are all flippers, but the two hind flippers of seals can only bend backwards, so they can only crawl on land.

Seals spend most of their time in the sea. Their bodies are spindle-shaped and have short hairs all over their bodies. Their forelegs are shorter than their hind feet, and there are nails on these flippers. Seals also have ears, but their ears have become very small and can be opened and closed freely when swimming. They are good at swimming, and their hind feet are like divers’ fins, which can swing back and forth in the water and move forward quickly. Seals dive for a long time, usually up to more than half an hour. When diving underwater, their heart rate will drop very low, which can reduce oxygen consumption.

Most seals live in cold waters, but they are not afraid of the cold, because they have a thick layer of fat, so seals usually like to live in places with ice in the North or South Pole. Seals also live in some sea areas of China, such as Bohai Sea. These sea areas freeze every winter, especially in Liaodong Bay and ice period for 130 days. These thick ice layers are inaccessible, and seals thrive here, the most of which are spotted seals.

These spotted seals are small, generally only 1.5 to 2 meters long. The maximum weight of males is 150 kilograms, while females are slightly smaller, about 100 kilograms. Their biggest feature is that their backs are covered with irregular brown-gray or brown-black spots, hence the name of spotted seals. They are very cute, so they are also permanent residents of the aquarium.

In the seal society, polygamy is practiced, so the number of wives and concubines usually depends on the male seal’s own physique. In order to compete for females, males often fight. Seals fight a bit like sumo. They use their hind legs to support themselves and try their best to pounce on each other. Sometimes seals will bite each other’s fur and blood will flow. At the end of the battle, the winner wins the right to mate, while the loser can only continue to look for the next female seal.

In early spring, baby seals will be born. At this time, we can see a young seal lying next to the female seal, which is very interesting. The young seal is raised by both parents, and the female seal is fed several times a day. Of course, the mother seal will only breast-feed her baby. If other baby seals come near, they will be rudely driven away. Some people may think that the mother seal is selfish, but this may be the law of nature.

The fat content in seal milk is very high, so baby seals will grow very fast. Young seals don’t have a thick layer of fat, but their hair is very fluffy and soft, and baby seals rely on these hairs to keep warm. But fluffy hair makes it inconvenient for them to swim, so baby seals rarely go into the water during lactation. Most of the fur of baby seals is white. From a distance, it is like snow, which is not easy to be found. They are not afraid of the cold and live a very leisurely life.

The lactation period of seals is not long, especially spotted seals, which only lasts for one month. After lactation, the mother seal will become skinny, and they will leave their children to recover. At this time, the seal family will end and the baby seal will begin to live independently in the water.

The leathers of seals are tough, comparable to cowhide, and can be processed into purses and leather shoes. Their thick fat can extract oil, and their meat is edible and has high nutritional value. In addition, the testicles of male seals are valuable Chinese herbal medicines, which have the effects of enriching blood and strengthening yang, and their livers are valuable tonics. Seals are all treasures, so they have always been the target of human hunting. Every spring, seals go ashore. In the 19th century, many countries used well-equipped ships to catch seals in the Antarctic, among which the crab-eating seals were the most caught. These hunting teams kill seals like crazy, and they can get tens of thousands of leopard skins from South Georgia in just one season.

Before the 1980s, fishermen along the Bohai Sea in China also had a tradition of killing spotted seals, but later legislation prohibited the killing of spotted seals, and now the population has recovered. In 2009, EU legislated to ban the trade of seal products, and Russia also banned the commercial seal slaughter.

Inventory of 4 major declared cars: Tesla Model 3 pushes up the performance version

Recently, a large number of new cars have been declared by the Ministry of Industry and Information Technology, including many car models. Among them, four new cars are highly concerned, namely Tesla Model 3 Performance, Extreme Yue 07, New Deep Blue SL03 and Mazda EZ-6.

1. Tesla Model 3 Performance

Tesla Model 3 Performance is also the high-performance all-wheel drive version of Tesla Model 3. The appearance of the new car continues the normal version, with a very simple front face and sharp headlights.

The side part of the car body adopts hidden door handles. In terms of size, the length, width and height of Tesla Model 3 Performance are 4724/1848/1430 mm and the wheelbase is 2875 mm, which is basically the same as the ordinary version.

The tail is duck-tailed and the taillights are sharp.

The interior is likely to continue the design of the "blank room" with cash.

In terms of power, the new car front induction asynchronous motor+rear permanent magnet synchronous motor, the comprehensive power of the system is 343 kW, the comprehensive torque is 723 Nm, and the 0-100 km/h acceleration time is 3.1 seconds.

2. Extreme Leap 07

Extreme Vietnam 07 is expected to be listed in the second half of 2024. In terms of appearance, the new car continues the family-style design language, and the front light group is very sharp. The closed grille adopts grid design.

The side part is not equipped with a door handle design, which looks very simple. In terms of size, the new car has a length, width and height of 4953/1989/1475 mm and a wheelbase of 3013 mm.

In terms of tail modeling, it adopts large slip back design and is equipped with through taillights.

In terms of power, the Extreme Yue 07 has a single motor version and a double motor board. The maximum output power of the single motor version is 200 kW, and the maximum power of the motors before and after the double motor version is 200 kW.

3, the new dark blue SL03

The name of the new dark blue SL03 may be changed to dark blue L07. In terms of appearance, it continues the current design style, and the front face is very radical and simple.

The side part of the car body adopts a hidden door handle design. The wheel hub is very stylish. In terms of body size, the length, width and height of the new dark blue SL03 are 4875/1890/1480mm and the wheelbase is 2900mm respectively.

In terms of power, the new dark blue SL03 pure electric version is equipped with a motor with a maximum power of 185kW. As a range extender, the extended-range 1.5L engine has a maximum power of 72kW and a peak power of 160kW.

4. Mazda EZ-6

The front face of Mazda EZ-6 adopts gradient grille design, and the headlights are very sharp. Add chrome-plated elements to the front enclosure.

The side part of the car body adopts a hidden door handle. In terms of dimensions, the length, width and height of Mazda EZ-6 are 4921/1890/1485mm and the wheelbase is 2895mm respectively.

The tail has a duck tail shape, and the taillights are designed through.

In terms of power, the Mazda EZ-6 pure electric version is equipped with a rear single motor with a maximum power of 190kW. The extended range version uses a 1.5L engine as the range extender, with a maximum power of 70kW and a motor power of 160kW.