Objective To understand the sensitivity of cytopathogenic effect (CPE) in MadinDarby canine kidney cells(MDCK) that cultured influenza A pharyngeal swab specimens of patients for one,two and three passages. Methods Influenza A pharyngeal swab specimens of patients were inoculated in MDCK for three blind passages. The presence of CPE of every passage was observed by inverted microscope. Results Of the 279 influenza A pharyngeal swab specimens of patients tested by colloidal gold, the presence of CPE in MDCK for one,two and three passages was 65.9%(184/279),91.4%(255/279) and 96.4%(269/279), respectively. Two hundred and seventy-one of 279specimens were identified as influenza A by multiplex reverse transcription-polymerase chain reaction (RT-PCR). Conclusion The positive separation rate can reach more than 95% by inoculating influenza A pharyngeal swab specimens of patients in MDCK for three blind passages.

Objective To establish a clinical test assay for detecting common respiratory viruses and enteroviruses (EV) by using mixed cultured Madin-Darby canine kidney cells (MDCK), human epidermoid cancer cells (Hep-2) and African green monkey kidney cells (Vero) to isolate common respiratory viruses and enteroviruses. Methods Throat swabs with influenza A and B viruses,adenovirus and EV71 were incubated with mixed cultured MDCK, Hep-2 and Vero in a single vial to observe the presence of cytopathic effects. Polymerase chain reaction (PCR), reverse transcription (RT)-PCR and monoclonal antibody-based immunofluorescene assay were also used for confirmatory test. Results The sensitive cell lines developed obvious cytopathic effects to the corresponding viruses, which were confirmed by the specific green particles observed by immunofluorescence assay and specific target PCR segments. Conclusions The shell-vial of mixed cells can simultaneously isolate different common respiratory viruses and EV. The isolated pathogens can be further confirmed by antigen test and PCR. This assay may improve the diagnosis of clinical viral diseases.

This article referred to the relevant guidelines for vaccine clinical trials and the accumulated experience in the development and review of human rabies vaccines, as well as combined the technical recommendations for human rabies vaccines from major health facilities such as WHO, to discuss the key considerations in the design of clinical trials for human rabies vaccines, including control vaccines, evaluation of efficacy endpoints, clinical subjects, the sample size, immunity persistence, re-exposure immunization schedule and post-marketing study. This article aimed to provide reference for the design of human rabies vaccine clinical trials.

Objective To investigate the changes and related factors of maternal thyroid autoantibodies during early pregnancy. Methods Urinary iodine concentration( UIC) , serum thyroid stimulating hormone( TSH) , free thyroxine ( FT4 ) , thyroid-peroxidase antibody ( TPOAb ) , thyroglobulin antibody ( TgAb ) concentrations were determined in 7 190 women during early pregnancy in an iodine-sufficient region of China. Results The prevalence of TPOAb positivity and TgAb positivity were 8. 7% and 12. 0% respectively. The prevalence of overt hypothyroidism and subclinical hypothyroidism increased significantly in group of thyroid antibody positivity. The prevalence of TPOAb positivity and TgAb positivity presented a U-shaped curve, ranging from mild iodine deficiency to iodine excess, especially increased significantly in the group with UIC<100 μg/L. Conclusion Prevalence of thyroid antibodies positivity became higher during early pregnancy. The positive thyroid autoantibodies during pregnancy were significantly associated with maternal hypothyroidism. Both iodine excess and iodine deficiency are risk factors of positive thyroid antibodies.

β-thalassemia is a single-gene genetic disease caused by β globin gene mutations leading to the fact that red blood cells are unable to form normal adult hemoglobin, and then patients develop hemolytic anemia. Current treatment regimens mainly include allogenetic hematologic stem cell transplantation, symptomatic regular blood transfusions and the use of iron removers to reduce iron load. Some severe patients have quite poor prognoses and deadly consequences if not treated timely. Genetically modified autohematopoietic stem cells can provide a new treatment option for patients with β thalassemia, which may achieve a long-term and stable increase in hemoglobin level through a single dose, making one-time cure β-thalassemia possible. This paper reviews the key elements of clinical trial design for β-thalassemia gene therapy from the aspects of efficacy evaluation endpoints, clinical trial design, enrollment population, and subject monitoring in order to provide a reference for pharma-therapeutic research and development enterprises.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we puts forward a series of thoughts and suggestions on the common problems of safety study on vaccine, including the hypothesis of safety study, the consideration of inclusion/exclusion criteria and suspension/termination criteria for study; the routine requirements of safety study and some special issue such as medical laboratory test index, vaccine virus shedding and safety of adjuvant, and further clarifies the requirements of safety observation on sequential enrollment; also emphasized the scientific judgment of causality and the quality of safety monitoring. It can be used for reference by vaccine researchers and to explore appropriate solutions to promote vaccine research & development and risk control in China.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we summarized the common problems in safety analysis and report and accordingly puts forward a series of thoughts and suggestions, including discussing the role of statistics in safety analysis, putting forward the framework of safety analysis and report involved analysis content, analysis index and analysis dimension, in which attention is paid to the severity analysis; emphasizing the initiative analysis on risk signal and encouraging the evidence-based initiative safety evaluation. At the same time, this paper discusses the basic principles of the presentation of safety data in the package inserts, as well as the comprehensive consideration of the safety data of each phase of the trial and different subjects. It can be used for reference by sponsor to promote vaccine clinical research and evaluation in China.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we puts forward a series of thoughts and suggestions on the common problems of safety study on vaccine, including the hypothesis of safety study, the consideration of inclusion/exclusion criteria and suspension/termination criteria for study; the routine requirements of safety study and some special issue such as medical laboratory test index, vaccine virus shedding and safety of adjuvant, and further clarifies the requirements of safety observation on sequential enrollment; also emphasized the scientific judgment of causality and the quality of safety monitoring. It can be used for reference by vaccine researchers and to explore appropriate solutions to promote vaccine research & development and risk control in China.

The safety of prophylactic vaccine is one of the key points both in clinical trials and evaluation. Based on the review practice of vaccine registration clinical trials in recent years, we summarized the common problems in safety analysis and report and accordingly puts forward a series of thoughts and suggestions, including discussing the role of statistics in safety analysis, putting forward the framework of safety analysis and report involved analysis content, analysis index and analysis dimension, in which attention is paid to the severity analysis; emphasizing the initiative analysis on risk signal and encouraging the evidence-based initiative safety evaluation. At the same time, this paper discusses the basic principles of the presentation of safety data in the package inserts, as well as the comprehensive consideration of the safety data of each phase of the trial and different subjects. It can be used for reference by sponsor to promote vaccine clinical research and evaluation in China.

Chimeric antigen receptor (CAR) T lymphocyte has shown attractive prospects in the treatment of lymphohematopoietic malignancies including B-cell lymphoblastic leukemia, B-cell lymphoma and multiple myeloma. Many applicants have submitted investigational new drug (IND) applications to Center for Drug Evaluation of National Medical Products Ggency, however, many of the INDs have problems in patient selection, prognostic indicators and risk management, etc, which might hinder the evaluation of the safety and efficacy of CAR-T cells. Thus, we made some suggestions on the above-mentioned problems through summarizing clinical experience and communicating with domestic clinical experts, which the sponsors and researchers can refer to when conducting CAR-T cell clinical trials for registration.