Objective:The study aims to gain information on medical research status and cooperative needs of medical universities/colleges from China and Association of Southeast Asian Nations (ASEAN) and provide evidence to guide the regional cooperation and development in medical reserach.Methods:A self-constructed questionnaire survey was adopted to collect information on the cooperative intentions, expertise and challenges of the 43 member institutions of China-ASEAN University Consortium on Medicine and Health in medical research.Results:In total, 20 Chinese members and 10 ASEAN members completed the survey. The study found that both Chinese and ASEAN medical universities/colleges were particularly interested in cooperation in academic conferences, multi-center clinical trials and joint research projects /flagship projects, followed by large cohort studies and medical journal/publication. In terms of research priority, both Chinese and ASEAN institutions were very interested in big data, followed by cancer precision medicine; while ASEAN members were more interested in natural drugs and dengue than Chinese ones.Conclusions:Both Chinese and ASEAN medical universities/colleges had strong interest in international cooperation in medical research. They should further explore the advantages and characteristics of both sides in medical research based on the interests of two sides, adopt appropriate scientific research cooperation methods, and establish sound scientific research cooperation mechanism so as to deepen cooperation in medical research, promote the development and improve the outcome of regional medical research, and facilitate the building of a community of common health for mankind.

Glutinous rice wine is a traditional food in south of China and it can coagulate milk. It has been proved that its function of coagulating milk is because of the presence of milk-clotting enzyme produced by microorganisms in glutinous rice wine. The aim of this work is to isolate milk-clotting enzyme producing strain from glutinous rice wine and study the fermentation condition. We screened out four bacteria and fungus by gradient dilution. It was proved that mold played the most important role in the production of milk-clotting enzyme. This is further confirmed by casein plate method. The optimization of fermentation conditions revealed that two times concentrated potato medium supplemented with 5% glucose without additional nitrogen was better for production of the enzyme. The enzyme activity was increased 144% under the conditions established.
Aspartic Acid Endopeptidases ; biosynthesis ; Bacteria ; isolation & purification ; metabolism ; Culture Media ; Fermentation ; Oryza ; metabolism ; Wine ; microbiology ; Yeasts ; cytology ; isolation & purification ; metabolism

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

OBJECTIVETo explore the immuno-effect of plasmacytoid dendritic cells (pDC) on bacteria infection induced spontaneous remission (SR) of leukemia.

METHODSBoth pDC and myeloid dendritic cells (mDC) were isolated and purified from leukemic patient with SR and healthy donor by combination of immunomagnetic beads and flow cytometry. pDC were cultured in RPMI1640 medium and stimulated with different bacteria. The T cells proliferation was detected by MTT, and cytokine production by ELISA kits.

RESULTSThe human bacterial pathogen Staphylococcus aureus and Pseudomonas aeruginosa stimulation for 48 h resulted in the maturation of pDC with production of high quantity of IFN-α at (15.34 ± 2.91) ng/ml and (10.38 ± 1.41) ng/ml, respectively, comparing with that of negative group at (1.36 ± 0.13) ng/ml (P<0.01). Activated pDC could promote the differentiation of naive CD4⁺ T cells to Th1 cells with secretion of IFN-γ at (2.16 ± 0.37) ng/ml and (2.73 ± 1.11) ng/ml, respectively, comparing with that of positive control at (2.55 ± 0.23) ng/ml (P > 0.05). Activated pDC showed higher T cell stimulatory capacities [proliferation index (PI) was 4.36 and 4.05, respectively] than that of non-activated pDC (PI was 1.23 and 0.13, respectively) (P < 0.01).

CONCLUSIONStaphylococcus aureus and Pseudomonas aeruginosa activated pDC may play a key role in SR of leukemia following severe infections.

CD4-Positive T-Lymphocytes ; Dendritic Cells ; immunology ; Flow Cytometry ; Humans ; Interferon-alpha ; Leukemia ; diagnosis ; immunology ; Lymphocyte Activation ; Pseudomonas aeruginosa ; immunology ; Remission, Spontaneous ; Staphylococcus aureus ; immunology