With the development of antibody manufacturing technology and improvement of new drug research in domestic industry, more innovative monoclonal antibody products submitted investigational new drug (IND) application. At the same time, monoclonal antibody products from abroad which have been approved marketing authorization and/or conducted clinical trials submitted IND applications in China. The National Medical Products Administration (NMPA) issued the "Guideline of Investigational New Drug Application" (No. 16, 2018) which emphasized the chemical, manufacturing, and control (CMC) regulatory, and dossier requirements in IND application, greatly promoted the application quality of innovative biological products. However, compared to the Food and Drug Administration (FDA) and European Medicines Agency (EMA), our particular guidelines are insufficient, such as guideline on virus safety evaluation of biotechnological investigational medicinal products. This review investigated the questions raised by sponsors from 2018 to 2020, including the end of production cell (EOPC) and/or unprocessed bulk (UPB) testing and virus removal or inactivation validation. Meanwhile, sponsors submitted different dossiers due to differences in understanding of stage requirements of guidelines from domestic and abroad. Based on the guidelines of virus safety from NMPA, FDA, and EMA, and the technical considerations, this review puts forward personal suggestions on the adventitious agents testing and virus removal or inactivation validation in manufacturing process, aim to ensure virus safety of innovative monoclonal antibody products in clinical trials.

Objective To observe the inhibitory action of Qigefang on cell proliferation,movement,secreting MMP-2 and MMP-9 of MGC gastric cancer cell line.Methods MGC cell line of gastric cancer was cultured and divided into five groups randomly:low-,middle-,high-dose group of Qigefang,5-FU group,control group.Qigefang was added in Qigefang group to make final concentration of 35,70,140 mg/mL,5-FU in chemothapy group to 50 ?g/mL,and PBS in control group.Tumor cell proliferation was detected by MTT,moving ablity of tumor cell by agar drop,and MMP-2,MMP-9 activity by gelatinase zymography.Results Qigefang had obviously depressant effect on proliferation of MGC cell.It became more obviously with raising drug density.Moving ability of all dose Qigefang groups and 5-FU group were more feeble than control group.The difference was significant(P

Objective To investigate the clinical and skeletal muscular pathological features of chronic progressive external ophthalmoplegia(CPEO).Methods The clinical and skeletal muscular pathological data of 6 patients with CPEO were analyzed retrospectively.Results All of the 6 patients onset were 4 to 18 years old.The first symptom was blepharoptosis.The clinical mainly manifestations were limited activity of eyeball,accompanied with limbs muscle fatigue,weakness and level elevatation of serum creatine kinase(CK).5 cases had myogenic changes in electromyography(EMG).The skeletal muscular pathological examination showed that the ragged red fibers(RRF)were scattered among the muscle fibers,and the deficient or absent of COX activity in many fibers.A few degenerating and necrotic fibers were observed in 4 cases.Lipid-drops were increased by oil red "O" stain in 3 cases.Electromicroscope showed that abnormal mitochondria increased in number and aggregated under sarcolemma or in cytoplasm.Crystalloid inclusion body could be observed.Conclusions The clinical mainly features of CPEO are external ophthalmoplegia and accompanied with limbs weakness.RRF and COX activity deficiency or absence according to skeletal muscle pathology can be suggest and support the diagnosis of CPEO.Gene sequencing based on skeletal muscle biopsy is necessary to make the final diagnosis of CPEO.

Objective To observe the regulatory effects of the preventive acupuncture and moxibustion at Guanyuan (RN4) points in ovariectomized rats, and discuss the mechanism of preventive acupuncture and moxibustion on hyoathalamus-pituitary-ovary (HPO) axis. Methods Totally 48 female SD rats were divided into 5 groups, including normal group, sham operation group, ovariectomized rats group, preventive acupuncture group and preventive moxibustion group. Except normal group and sham operation group, rats were ovariectomized after preventive acupuncture and preventive moxibustion for 30 d in corresponding groups. ELISA was used to determine the levels of E2, ER, GnRH, FSH and LH in the tissues including hypophysis, hypothalamus and uterus. Results Compared with the normal group, E2, ER and GnRH level in the tissue of the model group was significantly lower (P<0.01), the levels of FSH and LH increased obviously (P<0.01). Compared with the model group, E2, ER and GnRH level of preventive acupuncture group and preventive moxibustion group increased in different degree (P<0.05). FSH and LH level reduced in different degree (P <0.05). There was no obvious difference between preventive acupuncture and preventive moxibustion group (P>0.05). Conclusions The preventive acupuncture and preventive moxibustion at Guanyuan (RN4) has benign modulation to disordered HPO axis of ovariectomized rats. The ability of preventive acupuncture and preventive moxibustion are almost the same.

Female ; Genes, p53 ; immunology ; Humans ; Ovarian Neoplasms ; genetics ; pathology ; Ovary ; pathology ; Proto-Oncogene Proteins ; immunology ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Proto-Oncogenes ; immunology ; Sertoli-Leydig Cell Tumor ; genetics ; pathology ; ras Proteins ; immunology ; metabolism

Coloboma ; Humans ; Infant, Newborn ; Male ; Optic Nerve ; abnormalities

Objective To investigate the effect of treadmill running pretreatment on the expression of CyclinA and CyclinE protein in hippocampus of rats after global cerebral ischemia and reperfusion.Meth-ods 60 healthy male wister rats were randomly divided into control group, model group and experiment group.Global cerebral ischemia reperfusion model was generated by improved four-vessel occlusion as de-scribed according to the description of Pulsinelli's method.Rats in the experiment group were performed treadmill running for 2 weeks before injury.The water maze test was performed at 24 h and 48 h respectively after injury to determine the spatial memory ability of rats.Morphological changes of hippocampus were ob-served by HE staining ( hematoxylin-eosin staining) at 3 h,6 h,24 h,48 h after injury and the expression of CyclinA and CyclinE were detected by immunohistochemical staining.Results Compared with control group,the survival rate of neurons in the model group was significantly decreased at each time point.Morris water maze test showed that the escaping latency of rats in the model group was significantly prolonged( 24 h (24.35±3.99)s,48 h(33.08±5.85)s),and the frequency of crossing the platform was decreased(24 h(6.80 ±0.79),48 h(4.00±0.67)).The expression of CyclinA was increased significantly in the model group ((8.40±0.52)/high view,(11.70±1.06)/high view,(15.50±0.53)/high view,(22.40±0.52)/high view) as well as the expression of CyclinE((20.30±0.48)/high view,(15.20±0.63)/high view,(10.00± 0.82)/high view,(7.70±0.68)/high view) (P<0.05).Compared with model group,the survival rate of neurons in the model group was significantly increased at each time point.Morris water maze test showed that the escaping latency of rats in the experiment group was significantly shorten(24 h(13.21±2.73) s,48 h (24.20±4.66)s),and the frequency of crossing the platform was increased(24 h(9.70±0.95),48 h(6.30± 1.16)).The expression of CyclinA was significantly increased in the model group((10.60±0.84)/high view),(16.70± 0.68)/high view),(24.50±0.53)/high view),(36.20±1.40)/high view) as well as the expression of CyclinE((31.60 ±0.70)/high view),(24.50±0.70)/high view),(16.80±0.63)/high view),(9.10±0.74)/high view) (P<0.05).Con-clusion The treadmill running pretreatment improves the function of spatial memory after global cerebral ischemia and reperfusion,potenlially mediated by regulating the expression for cell cycle proteins,which have a protective effect on cerebral brain tissue.

Objective To examine the teaching effects of case-based learning in the class of functional experiment. Methods Students (n=139) of five-year clinical medicine specialty were ran-domly divided into control group (n=70) and case group (n=69). The students of control group were taught with traditional teaching method and the case-based learning was adapted in the case group. Namely the clinical cases were led into teaching and the teaching process was completed through case import, problem sets, and the literature review and discussion. The teaching effects were evaluated through questionnaire survey (Analysis by the χ2-test, the test level is 0.05) and the analysis of test scores (Analysis by the t-test, the test level is 0.05). Results The score of the case group was better than the control group in the operation test (P=0.042 0). The total evaluating score and test score were also better in the case group in comparing to the control group (P=0.007 8 or P=0.008 2). As indicated by the questionnaire survey, more than 80%students thought the case teaching method could improve their learning interests and the independent learning abilities. Moreover, the skills of problem analysis and knowledge application were increased through case teaching. Conclusion The teaching effects of case-based learning were superior to the traditional teaching.

Laboratory opening pattern was researched in order to increase the practical ability and spirit of innovation. The study focused specifically on teaching form,teaching method and evaluation systems in laboratory opening.Surver research was made in students and showed good effects.

Objective To provide the experimental evidence for clinical application of taurine,rat model of intrauterine growth restriction (FGR) was made to investigate influence of prenatal administration of taurine on neurogenesis.Methods Fifteen pregnant rats were divided into control,FGR model and taurine groups,5 rats for each group.Rats in the control group were supplied with unlimited food and drink while the other two groups were fed by 40％ food intake of the control group throughout pregnancy.Since gestational day 12,taurine (100 mg/kg) was added into diet of taurine group every day until term delivery.Brain tissues were obtained immediately after baby rats were born.Expression of proliferating cell nuclear antigen (PCNA),neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) of brain tissue was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry; meanwhile,numbers of PCNA-immunoreactive cells in subventricular zone,subgranular zone and cerebral cortex were compared with ANOVA test or q test.Results Levels of PCNA mRNA and GFAP mRNA expression in FGR group were significantly higher than those of control group (PCNA mRNA:1.002±0.011 vs 0.894 ± 0.040,P＜0.01; GFAP-mRNA:1.012±0.013 vs 0.913±0.012,P＜0.01).Compared to FGR model group,mRNA expressions of PCNA and GFAP in taurine groups were higher (1.090±0.029,P＜0.01 ; 1.034±0.011,P＞0.05).There was a significant decrease in the expression of NSE mRNA in FGR group compared with control group (0.796±0.036 vs 1.582±0.057,P＜0.01),while the expression in taurine group (0.933±0.027) was significantly higher than that in FGR model group (P ＜ 0.01).PCNA immunoreactive cells were mostly distributed in subventricular zone,followed by subgranular zone and cerebral cortex.Conclusions Prenatal application of taurine could enhance neurogenesis of FGR newborn rats and improve survival of neurons to ameliorate FGR brain damage.