Objective To investigate the influence of atorvastatin combined with trimetazidine therapy on blood rheology and endothelial function in elderly patients with unstable angina pectoris.Methods 94 elderly patients with unstable angina pectoris were randomly divided into two groups.Group 1 was treated with ordinary thera-pies,while group 2 was treated in addition of atorvastatin in combination with trimetazidine.The Patients'clinical effects,blood rheology,endothelial function before and after treatment was compared between the two groups.Results The effective rate of group 1 was 74.5%,which was significantly higher than that of group 2(93.6%,P =0.011). The improvement of abnormal ECG turned to be the same result (80.9%,93.6%,P =0.008).There was no differ-ence between the two groups in all above indices (t =0.289,P =0.774;t =0.218,P =0.828;t =0.382,P =0.703;t =0.616,P =0.540;t =1.096,P =0.276;t =0.221,P =0.825;t =0.406,P =0.685).After treatment,the levels of blood and plasma specific viscosity and endothelin-1 in both groups all decreased (group 1:t =6.180,P <0.01;t =10.002,P <0.01;t =4.532,P <0.01;t =4.303,P <0.01;t =4.239,P <0.01;VS group 2:t =15.108,P <0.01;t =14.798,P <0.01;t =7.653,P <0.01;t =7.981,P <0.01;t =8.461,P <0.01),the levels of nitric oxide and FMD all significantly increased (group 1:t =3.627,P <0.01;t =4.833,P <0.01;VS group 2:t =9.945,P <0.01;t =9.707,P <0.01 ),and there was a significantly difference between 2 groups(t =8.750,P <0.01;t =4.388,P <0.01;t =3.415,P <0.01;t =5.132,P <0.01;t =3.052,P =0.003;t =5.754,P <0.01;t =4.503,P <0.01).Conclusion Atorvastatin combined with trimetazidine has an excellent effect on elderly unstable angina pec-toris,with significantly improving blood rheology and endothelial function.

The national standards for biological products include three types of reference materials,vaccines,biotherapeutics,and diagnostics,among which the national standards for vaccines play a crucial role in the production,issuance,and supervision inspection of vaccines. In recent years,the vaccine industry in China has developed rapidly,and especially,the application of new technology platforms such as mRNA in vaccines has highlighted the urgency of further improving the level of national standards for vaccines in China. Referring to WHO(World Health Organization)development requirements for reference materials of vaccines and taking Chinese national standard for SARS-CoV-2 neutralizing antibody as example,this paper summarized the thinking on national standards for vaccines in China,and presented the priority principles of establishing national standards for vaccines which are not traceable to WHO international standard(IS),in view to provide ideas for the further improvement of development and application of national standards for vaccines in China.

At present, the mode of Drug Quality Management has developed from the mode of“Quality by Test”and“Quality by Manufacture”to the mode of“Quality by Design”, emphasizing the application of risk assessment, process control, continuous monitoring and improvement in the production process. The concept of“Quality by Design(QbD)”has been widely used in the field of therapeutic monoclonal antibodies, but less in other biological products, especially in vaccines, which is due to the complex structure of vaccine, traditional technologies and the large variability of quality control methods. It is of great significance to speed up the implementation of the concept and framework of QbD for improving the quality, safety and efficacy of vaccines, especially new vaccines in China. In this paper, the application progress of QbD in vaccine research and development has been reviewed, and the existing problems and challenges have been analyzed, so as to provide a reference for promoting the application of QbD concept in vaccine industry and further improving the level of vaccine development and quality control in China.

Reference materials for vaccine are the standard rulers for quality control,dose determination and effectiveness evaluation of vaccines. Manufacturer's reference materials are a kind of the working standards that are directly used by vaccine enterprises in the process of production,quality control and evaluation,of which the accuracy and stability play a key role in ensuring the consistency between batches,safety and effectiveness of vaccines. Based on the investigation into the current management situation of manufacturer's reference materials in domestic representative vaccine enterprises,and combined with the relevant guidelines and regulations such as World Health Organization guidelines and Chinese Pharmacopoeia,this paper put forward the key points that should be considered in the establishment and application of manufacturer's reference materials of preventive human vaccines. It is also suggested to formulate the guidelines about manufacturer's reference materials in order to regulate the development and application of working reference materials.

Reference material is a kind of criteria“ruler”for the quality control and evaluation of biological products. WorldHealth Organization(WHO) technical reports and guidelines, China's management regulations about biological referencematerials and Chinese Pharmacopoeia play an important guiding role in the development,distribution and use of standards. Inorder to meet the needs of the development of the biological product industry, WHO guidelines and Chinese national manage-ment regulations about biological reference materials have been revised for several times. This paper summarizes the evolu-tion and current situation of the definition, classification and technical requirements for WHO international biological stan-dards and national biological standards in China, aiming to further improve the preparation and application of national biologi-cal reference materials in China.

Stability represents a critical quality attribute of reference materials. To ensure the stability of biological reference standards, World Health Organization(WHO) has continuously refined and elaborated the stability requirements in guidelines for both international(primary) and national(secondary) biological reference materials, aiming to enhance the scientificity and operability of stability studies and monitoring. Based on a summarization of the WHO guidelines on stability studies for biological reference standards and case studies of international reference standards development documented in the literature, this paper proposes considerations and recommendations for improving stability studies and stability monitoring of national biological reference standards in China.

Targeted agents for small cell lung cancer (SCLC)include inhibitors of angiogenesis,tyro-sine kinase inhibitors and signal transduction pathway inhibitors.Bevacizumab,a class of antiangiogenic agent, tends to have no effects on patients.The tyrosine kinase inhibitor,for example sunitinib,may be used as a monotherapy.Signaling inhibitors including Amuvatinib and LDE225 are undergoing phaseⅠand Ⅱ trials.Pri-mary data show that SCLC is not sensitive to targeted therapy,needing more selection,so further studies are requested.

Objective To compare the overall diagnostic accuracy of MRCP with EUS for the detection of choledocholithiasis and malignant obstruction in patients with suspected biliary obstruction.Methods A fully recursive literature search was conducted in The Cochrane Central Register of Controlled Trials CENTRAL,MEDLINE or PUBME (1980-2012),EMBASE (1980-2012),OVID Database (1980-2012),CBM (1980-2012),VIP database (1989-2012),Chinese journal of full-text database (CNKI) (1980-2012),and WANFANG database(1980-2012).The prospective diagnostic studies which evaluated or compared the diagnostic accuracy of MRCP and EUS were included combined with manual searches.We also searched the references of all included articles of important meetings and journals.QUA-DAS items were used to evaluate the quality of the included studies.SEN,SPE,+ LR,-LR and the areas under SROC were detected,then t-test was used to evaluate whether statistically significant difference existed between EUS and MRCP.Results Thirteen studies including 1200 cases were recruited.The overall pooled sensitivities of MRCP and EUS for the detection of choledocholithiasis were 0.870 (95％ CI:0.826-0.906)and 0.935 (95％ CI:0.90-0.96) respectively,whereas their specificities were 0.952 (95％ CI:0.926-0.971) and 0.947 (95％ CI:0.920-0.967),respectively.The overall pooled positive likelihood ratio for MRCP and EUS were 14.055 (95％ CI:6.259-31.561) and 16.653 (95％ CI:6.896-40.212),respectively,with the corresponding negative likelihood ratio of 0.177 (95％ CI:0.108-0.290) and 0.076 (95％ CI:0.049-0.118),respectively.Areas under the ROC curve were 0.9693 and 0.9771,respectively.There were no statistically significant difference for sensitivity (0.84 ± 0.16 vs 0.93 ± 0.07,P =0.108) and specificity (0.93 ±0.10 vs 0.90 ±0.15,P =0.555) between MRCP and EUS.The overall pooled sensitivities of EUS and MRCP for the detection of malignancy were 0.959 (95％ CI:0.908-0.987),and 0.805 (95％ CI:0.724-0.871),respectively,whereas their specificities were 0.975 (95％ CI:0.954-0.988) and 0.927 (95％ CI:0.897-0.951),respectively.The overall pooled positive likelihood ratio for EUS and MRCP were 23.398 (95％ CI:12.987-42.155) and 13.448 (95％ CI:4.961-36.456),respectively,with the corresponding negative likelihood ratio of 0.059 (95％ CI:0.028-0.122) and 0.134(95％ CI:0.046-0.391),respectively.Areas under the ROC curve were 0.9870 and 0.9686,respectively.There were no statistically significant differences for sensitivity (0.95 ± 0.55 vs 0.88 ± 0.14,P =0.22) and specificity (0.96 ±0.03 vs 0.91 ±0.11,P =0.31) between MRCP and EUS.Conclusion MRCP and EUS are both valuable in differential diagnosis of biliary obstruction caused by choledocholithiasis or malignant lesions.

Objective To investigate the effects of combination of aniso-dosage of Astragalus and Arctium on the glycolipin metabolism and renal lesion in diabetic rats.Method Streptozotocin (STZ)-induced diabetic rats were established as experimental model.The diabetic rats were randomized into model group and mixture-treated group.Astragalus and Arctium were divided into three dosages (low,moderate,high) respectively and combined according to orthogonal experimental design and were administrated to the mixture-treated group.At the 4th and 8th week,parameters of blood,urine and renal tissue were examined.The blood sugar,cholesterol,triglycerol,HbA1c were detected by analysis meter of biochemistry,urine microalbumin by radioimmunoassay (RIA) and 24 h urine protein by colorimetry.The HE and PAS staining were used to observe the change of glomerular ECM.Results At the 4th weekend,the combination of Arctium high-dosage had better effects on decreasing blood sugar and cholesterol.While at the 8th weekend,the effects of mixture were gradually augment with the Astragalus dosage increasing on decreasing triglycerol,24 h urine protein and ECM.Conclusion The compatibility of aniso-dosage of Astragalus and Arctium could rectify the metabolic disturbance of glycometabolism and lipid metabolism,and lessen the renal lesions.The compatibility had different effects on various experiment phases.

AIM: To investigate the influence of Fructus Arctii and its extracts to the renal pathological changes of diabetic rat and its protective mechansim METHODS: The rat model induced by 55mg/kg STZ once intraperitoneally was adoped as the diabetic nephropathy of early stage, the extract and the powder of Fructus Arctii were given to the diabetic rat for six weeks. We observed the changes of general condition, and examined the expressions of TGF-? 1 (transforming growth factor-? 1) mRNA and MCP-1mRNA (monocyte chemoattractant protein-1) by reverse transcription-polymerase chain reaction (RT-PCR). CONCLUSION: The ethanol extract of Fructus Arctii relieved renal pathological changes of diabetic rat. The mechanism perhaps was related to the reduction in the expression of MCP-1mRNA and TGF-? 1mRNA in kidney; The study proved that the ethanol extract of Fructus Arctii was more effective than its water extract and coarse powder.