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 investigate the technical charactenstics ot SYSMEX XS1000i 5-part differential automated hematological analyzer and its clinical applications.Methods 209 samples were analyzed with the analyzer of XS1000i and compared to the results from Beckman-Coulter LH750 analyzer.The main parameters from XS1000i,such as precision within-run,day to day precision and carryover contamination rates etc,were recorded respectively in 509 samples to compare the difference between the instrumental and optical examination.Results All variation coefficients of precision from XSI000i were within the manufacturer.The carryover contamination rates of WBC,RBC,Hb,HCT and PLT were 0.19%,0.93%,0,-0.88%,-0.76%,respectively.The parameters of XS1000i were correlated with the results of LH750 except basophil granulocyte.The correlation coefficients of WBC,RBC, HGB and PLT were 0.994 5,0.996 8,0.997 0 and 0.974 6 ,respectively.The sensitivity of warning flags in immature leukocytes was 100% and the specificity was 69.7%,the sensitivity of warning flags in atypical lymphocyte was 100% and the specificity was 66.7%.Especially in 3 leukocytopenia that was induced by chemotherapy in patients with leukemia who had only few immature cells existed in the peripheral blood,the parameters of XS1000i were positive,and correlated with the results of detection of minimal residual disease with flow cytometry.Conclusions The warning system of XSIO00i provides more valuable information for manual microscopic examination.If it is combined with flow cytometry,the advantages in detection of residual leukemic cell will be fully displayed.

Radiotherapy is an importment local treatment for non-small cell tung cancer. In recent years,with the development of molecular biology and radiotherapy technique and the update of equipment,radiation pattern with different doses segmentation and the concept of the combined therapy including radiotherapy and chemotherapy have been applied in clinic gradually,which get better effects.

Objective To investigate the role of NFIC on the stimulation effects of cAMP-induced differentiation of stem cells from the apical papilla ( SCAPs) in vitro. Methods SCAPs isolated from dental papilla of human imma-ture third molars were cultured by enzyme digestion. SCAPs were transfected with lentivirus that overexpressed NF-IC gene ( ov-NFIC) or an empty vector ( LV-empty) and co-treatment with Forskolin. Mineralized nodule formation of each group was measured by alizarin red staining. Quantitative real-time reverse-transcription polymerase chain reaction was performed to test the expressions of RUNX2,ALP,OCN mRNA. Results Forskolin increased the ex-pression of Runx2, ALP, OCN mRNA as well as matrix mineralization in SCAPs, and the stimulation effects of For-skolin were enhanced by overexpressing NFIC gene. Conclusion The results indicate that NFIC can promote cAMP-induced differentiation of SCAPs.

Objective To investigate the characteristic of theta oscillation in patients with frontal lobe epilepsy (FLE) by the analysis of multi-channel electroencephalographs (EEGs) during rest state and working memory(WM) maintenance. Methods The 19 FLE patients and 17 healthy subjects underwent EEG recording with 34-channel EEG machine during visual working memory task performance. The differences of behavioral results were analyzed between FLE group and controls. Short-time Fourier transform was used to calculate the power spectral density of different frequency bands in 34 channels. The theta power values during the retention period of working memory and rest state were compared between two groups. Results Compared with controls, reaction time of FLE increased significantly (P<0.01) and accuracy decreased (P<0.05). The power spectral density of theta band for FLE increased both in Fz and frontal region during rest state (P<0.01). Compared with controls, the power spectral density of theta oscillation decreased significantly in the frontal region for FLE during WM maintenance. Conclusion Our results suggest that working memory in patients with FLE was impaired. The absence of theta oscillation during the WM delayde period may provide a possible neural mechanism for the working memory dysfunction in FLE.

Objective To evaluate the effect and clinical value of ultrasonography-guided Argon-Helium targeted ablation on treatment of liver tumor.Methods By means of ultrasound inducing,217 patients of liver tumors were selected for percutaneous Argon-Helium targeted cryoablation.Results All of liver hemangioma shrank in different degrees after cryoablation; 12 cases of small hepatic cancer were followed up for over one year,the one-year survival rate was 83.3% (10/12). 82.1% (165/201) advanced patients became better and clinical symptom ameliorated.One hundred and seventy-five cases of advanced patients were followed up for over one year,the one-year survival rate was 69.7% (122/175).The common complications after Argon-Helium cryoablation treatment were hemorrhage( 3.7% ,8/217), pleural effusion( 2.8% , 5/217). Conclusions Ultrasound-guided Argon-Helium targeted ablation in treatment of liver tumor is simple,safe and effective.

Objective To explore the relationship between plasma mannose-binding lectin (MBL), lipopolysaccharide (LPS) and body mass index in pregnant women with gestational diabetes mellitus (GDM). Methods 45 newly diagnosed GDM pregnant women and 45 healthy women (control group) were selected in this study. Plasma concentration of MBL and LPS were measured. All the groups were sub-divided into obesity (BMI ≥ 25 kg/m2) and non-obesity (BMI < 25 kg/m2) subgroup. The relationships of levels of plasma LPS, MBL with BMI were analyzed. Results The level of plasma MBL in GDM group was significantly lower than that in control group(P < 0.05), while the concentration of LPS in serum was much higher than that in healthy pregnant women (P < 0.05). Pearson analysis showed the level of MBL in GDM group was negatively correlated with BMI(r=-0.28, P<0.05), serum LPS concentration was positively correlated with BMI(r = 0.62, P < 0.05) and LPS was negatively correlated With MBL(r = -0.43, P < 0.05) . The above correlations were not found in control group. Conclusion Serum MBL and LPS maybe two important risk factors for those pregnant women being overweight, and could offer great significance for the prevention and treatment of GDM.

Objective To investigate the diagnostic value of breast MRI in patients presenting with microcalcifications on mammography.Methods Eight four patients were retrospectively analyzed,who had mammographically detected BI-RADS (breast imaging reporting and data system) 3 to 5 microcalcifications and underwent breast MRI before surgical biopsy.All mammography and MR images were reviewed with BI-RADS.With histopathological diagnosis as golden standard,the sensitivity,specificity and accuracy of the two methods were calculated and compared with x2 test or Fisher exact test.The diagnostic efficacy of the two methods was compared with ROC curve.Results Pathologic examination revealed 91 lesions in 84 patients including 49 benign lesions and 42 malignant lesions.For 21 lesions of category 3 microcalcifications,the specificity of mammography and MR was 100.0％ (21/21) and 95.2％ (20/21),which had no significant difference (P=1.000).For 51 lesious of category 4,sensitivity,specificity and accuracy of mammography were 100.0％(23/23),0 and 45.1％(23/51).The corresponding values for MR were 91.3％(21/23),82.1％ (23/28) and 86.3％ (44/51).The difference for specificity and accuracy between the two methods was statistical significant(x2 value was 30.030 and 19.182,respectively,with P＜0.01),but not for sensitivity(x2=0.523,P=0.470).Nineteen lesions of category 5 were all correctly diagnosed on mammography and MRI.For all the 91 lesions,the sensitivity,specificity and accuracy of mammography were 100.0％(42/42),42.9％(21/49) and 69.2％(63/91),respectively.The corresponding values for MRI were 95.2 ％(40/42),87.8％(43/49) and 91.2％(83/91).There was significant difference for specificity and accuracy between the two methods (x2 value was 21.798 and 13.851,respectively,with P＜0.05),but not for sensitivity (x2=0.512,P=0.474).The areas under ROC curve for mammography and MR were 0.844,0.945(P＜0.01),for the estimation of the benign and the malignent.Conclusions Compared with mammography,breast MRI significantly improved the diagnosis of category 4 microcalcifications with increased specificity and accuracy.But for microcalcifications of category 3 and 5,MR didn't improve the diagnostic effect.

Background and purpose:Progranulin (PGRN) is a novel growth factor that plays an important role in the tumorigenicity, tumor cell migration and cell cycle. Its expression in many malignant tumor cells is high. It is not only involved in tumor cell growth, but also closely related with the occurrence and evolution of tumor. This study was to investigate the expression of PGRN in gastric cancer and the effects on proliferation and senescence in gastric cancer cell line BGC823. Methods:Immunohistochemical method was used to detect the expression of PGRN in gastric cancer tissues and adjacent normal tissues; Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of PGRN in PGRN-siRNA BGC823 cells;MTT method, cell colony formation and cell senescence experiments were used to explore the effects of PGRN on proliferation and senescence in BGC823 cell. Results:PGRN protein levels were high in gastric cancer tissues;Knocking down the PGRN gene in BGC823 decreased the proliferation and clonogenic capacity, cloning efifciency in PGRN-siRNA group was (25.3±3.1)%, in the control group was (72.1±5.7)%, and in the normal cells was (80.3±4.0)%, there was no signiifcant difference between normal group and control group, but there were signiifcant differences among PGRN-siRNA group and the other two groups (P<0.05);Knocking down the PGRN gene in BGC823 cells could promote cell senescence. The positive rate of aging in PGRN-siRNA group was (27.6±2.1)%, in the control group was (3.2±1.3)%, and in the normal group was (1.9±1.2)%, there was no signiifcant difference between normal group and control group. But there were signiifcant differences among PGRN-siRNA group and the other two groups (P<0.05). Conclusion:PGRN can be used as a new marker for gastric cancer, and provide new ideas to the treatment of gastric cancer.

Objective To investigate the changes and correlation of retinol binding protein 4 (RBP4) and homocysteine (Hcy) levels in patients with diabetic retinopathy (DR).Methods 124 cases selected from the department of endocrinology admissions of patients with type 2 diabetes,divided into diabetic patients with non proliferative retinopathy group (NPDR group,40 cases),diabetes with value-added retinopathy group (PDR group,41 cases),diabetic retinopathy group (NDR group,n=43) and healthy volunteers group (NC group,40 cases),fasting venous blood indexes,correlation and multiple regression analysis in parallel.Results The RBP4,Hcy in PDR group were higher than NPDR group and NDR group,the difference was statistically significant(P<0.05);The RBP4 and Hcy in NPDR group were higher than NDR group,the difference was statistically significant(P<0.05);RBP4 and FPG,HbA1c,TC,TG,LDL-C and Hcy showed a positive correlation(P<0.05),and HDL-C showed a negative correlation(P<0.05),FPG and Hcy;HbA1c,TC,TG,LDL-C and RBP4 showed a positive correlation(P<0.05),and HDL-C showed a negative correlation(P<0.05);multi factor regression analysis,diabetic retinopathy and Hcy,RBP4 and HbA1c showed a positive correlation(P<0.05).Conclusion The levels of Hcy and RBP4 in patients with DR are highly expressed,and gradually increase with the progression of the disease,which is positively related to the occurrence and development of DR,and can be used as an important risk factor.