SUMMARY National Institutes of Health (NIH) released the biomedical research project NIH Roadmap Initiatives, including 3 themes, new pathways to discovery,research teams of the future,and re-engineering the clinical research enterprise. The purpose of the project is to catalyze to transform our new scientific knowledge into tangible benefits for people. Now,Mostly of the Project have begin to carry into practice.

Objective To investigate the effect of Eicosapentaenoic scid (EPA) on the sensitivity of glioma cell line U87 to temozolomide (TMZ) and the mechanism behind this effect.Methods U87 cells were randomly divided into four groups:control group,TMZ group,EPA+TMZ group and endoplasmic reticulum stress (ERS) activation tunicamycin group (EPA+TMZ+TM group).MTT method was used to evaluate inhibition ratio of cell proliferation.The apoptotic ratio was examined by flow eytometry.Western blot was used to detect the protein expressions of apoptosis cytokines (caspase-3 and Bax) and ERS cytokines [glucose-regulated protein 78 (GRP78) and inositol-requiring enzyme 1 (IRE-1)].Results EPA causes concentration-dependent and time-dependent inhibition of the cell proliferation (all P=0.00).EPA significantly enhanced the sensitivity of glioma cell line U87 to temozolomide.Compared to TMZ treatment alone,the inhibition ratio [(56.27+6.15)％ vs.(42.32±4.12)％,P=0.03] and apoptotic ratio [(49.78±5.94)％ vs.(37.74± 4.24)％,P=0.04] of U87 cells were enhanced by EPA+TMZ treatment.Western blot showed that the expression of apoptotic factor caspase-3 and Bax proteins were increased by EPA+TMZ treatment,while the protein expressions of ERS-related factors (GRP78 and IRE-1) were significantly inhibited (P=0.01).However,the salutary effects of EPA were reversed by ERS activation tunicamycin.Conclusion EPA enhances the sensitivity of glioma cell line U87 to temozolomide,the mechanism of which may be the suppression of ERS response.

Objective:To analyze the overall layout of coronavirus genetics research in the past 20 years from the perspective of publication time, journals, keywords, citations and funds, identify core research institutions and their cooperation networks in this field, and explore current research hotspots.Methods:PubMed and Web of Science databases were searched separately for the research literature and citations data about coronavirus genetics from 2003 to 2021, and Excel was used to analyze the distribution of the literature and institutions, and then the Citespace software was selected for institutional cooperation network and reference co-citation cluster analysis.Results:The literature about coronavirus genetics had increased significantly in 2020. The top 10 journals have collected 23.4% of relevant literature. Chinese Academy of Sciences has published the most documents in this field, in the top 10 high-yielding institutions, 7 are from China. In the cooperation network, the Chinese Academy of Sciences, University of Hong Kong and University of Sao Paulo have high betweenness centrality. The total litation times and average citation times of funded papers were higher than those of non-funded papers. There have been 7 research hotspots in the past 20 years. The research on " the gene sequence and functional receptors of the Middle East respiratory syndrome coronavirus" , " the gene traceability and drug development of the SARS-Cov-2" as well as " genotyping, origin and economic impact of paroxysmal porcine epidemic diarrhea virus in the United States" are still active in the past five years.Conclusions:Coronavirus genetics research will be at a sustained high level in the next few years or even longer. It is difficult to publish papers in journals with high impact factors (IF>5.00) in related fields. Chinese research institutions are active in this field. The Chinese Academy of Sciences and the University of Hong Kong are the most influential, and they have the closest cooperation with other institutions. The genetic tracing, gene sequence and functional receptor of coronavirus and drug development are likely to be the forefront of the research in this field.our govermment should advance the layout in this field and increase the number of research funds and financial support.

Objective To investigate the effect of endoplasmic reticulum stress on sensitivity of glioma cell line U87 to temozolomide (TMZ) and underlying mechanism.Methods (1) Glioma U87 cells were routinely cultured for 24 h in vitro;different concentrations of TMZ (0,12.5,25,50,100 μmol/L) were added to intervene the cell proliferation of U87 cells for 24 h;MTT method was used to detect the cellular proliferation inhibition rate,and half maximal inhibitory concentration (IC50) of TMZ was calculated;tunicamycin (TM) treatment (0,2,4,8 μmol/L) was given to the cells for 6 h,and then,50 μmol/L TMZ was given for 24 h,and cellular proliferation inhibition rate of U87 was detect by MTT method.(2) U87 cells were randomly divided into control group,TM group,TMZ group and TM+TMZ group;pretreatment of TM for 6 h was given to cells from TM group and TM+TMZ group;and 50 μmol/L TMZ was given to cells from TMZ group and TM+TMZ group;same amount of medium was given to cells from control group;24 h after treatment,the apoptotic rate was examined by flow cytometry;Westem blotting was used to detect the protein expressions of caspase-3,B-cell lymphoma 2 associated X protein (Bax),O-6-methlguanine-DNA methyltransferase (MGMT),glucose-regulated protein 78 (GRP78),and inositol-requiring enzyme 1 (IRE-l).Results (1) MTT showed that IC50 of TMZ was 50 μmol/L.As compared with that of 0 μmol/L TM+50 μmol/L TMZ group or 2 μmol/L TM+50 μmol/L TMZ group,the cellular proliferation inhibition rate of 4 μmol/L TM+50 μmol/L TMZ group and 8 μmol/L TM+50 μmol/L TMZ group was significantly decreased (P＜0.05).(2) As compared with TMZ group,TM+TMZ group had significantly decreased apoptotic rate (46.98％±4.79％ vs.35.74％ ±4.09％),significantly decreased caspase-3 and Bax protein expressions,and significantly increased MGMT,GRP78 and IRE-1 protein expressions (P＜0.05).Conclusion Endoplasmic reticulum stress can increase the resistance gene MGMT expression,decrease the chemotherapy sensitivity to TMZ,and induce chemoresistance ofglioma cell line U87.

BACKGROUND/OBJECTIVES: This study examined the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood during the 1959–1961 Chinese Famine. SUBJECTS/METHODS: A total of 3,418 individuals aged 35–74 years free of diabetes from two studies in 2006 and 2009 were followed up prospectively in 2009 and 2012, respectively. Famine exposure was classified as unexposed (individuals born in 1962–1978), fetal exposed (individuals born in 1959–1961), child exposed (individuals born in 1949–1958), and adolescent/adult exposed (born in 1931–1948). A logistic regression model was used to assess the relationship between famine exposure and diabetes after adjustment for potential covariates. RESULTS: During a three-year follow-up, the age-adjusted incidence rates of type 2 diabetes were 5.7%, 14.5%, 12.7%, and 17.8% in unexposed, fetal-exposed, child-exposed, and adolescent/adult-exposed groups, respectively (P < 0.01). Relative to the unexposed group, the relative risks (95% confidence interval) for diabetes were 2.15 (1.29–3.60), 1.53 (0.93– 2.51), and 1.65 (0.75–3.63) in the fetal-exposed, child-exposed, and adolescent/adult-exposed groups, after controlling for potential covariates. The interactions between famine exposure and obesity, education level, and family history of diabetes were not observed, except for the urbanization type. Individuals living in rural areas with fetal and childhood famine exposure were at a higher risk of type 2 diabetes, with relative risks of 8.79 (1.82–42.54) and 2.33 (1.17–4.65), respectively. CONCLUSIONS These findings indicate that famine exposure in early life is an independent predictor of type 2 diabetes, particularly in women. Early identification and intervention may help prevent diabetes in later life.

Objective To explore the clinical differences between patients with early-onset myasthenia gravis (EOMG)and those with late-onset myasthenia gravis(LOMG).Methods This was a retrospective study enrolling 157 MG patients.Based on the age of onset,patients were divided into the EOMG group(n=85)and the LOMG group(n =72).The groups were compared on clinical characteristics,including clinical manifestations,MG classification,electrophysiological findings on repetitive nerve stimulation(RNS),single fiber electromyography(SFEMG),levels of antibody against acetylcholine receptors(Ach-R Ab),antibody to muscle-specific kinase(MuSK Ab),titin antibody(Titin Ab),ryanodine receptor antibody(RyR Ab),thyroid function,thymectomy,thymus pathology and responses to treatment.Results The mean ages of onset were markedly different [(40.9 ± 9.7) years vs.(62.0 ± 12.2) years,P＜ 0.05] between the EOMG and LOMG groups.The LOMG group was associated with a significantly higher rate of the ocular form(50.0 ％,n=36 vs.32.9％,n=28,P＜0.05),a lower rate of the general form(50.0％,n=36 vs.67.1％,n=57,P＜0.05),and an increased risk of bulbar involvement(41.7％ n=30 vs.23.5％,n=20,P＜0.05)than those in the EOMG group.There was no significant difference in positive rates of RNAS and SFEMG,and levels of AChR Ab,MuSK Ab and double serum negative(DSN)MG between the groups (P＞0.05).Moreover,patients in the EOMG group were more likely to have abnormal thyroid function and higher percentages of receiving steroids,tacrolimus,plasma exchange therapy,and thymectomy (P＜ 0.05).Conclusions The clinical profiles of LOMG are different from those of EOMG in clinical manifestations,thyroid function,thymectomy frequency,striational antibody levels and disease-modifying drug options.

Objective:To analyze the clinical features and mutation of myeloid differentiation factor 88 (MYD88) L265P in patients with diffuse large B-cell lymphoma (DLBCL) of central nervous system (CNS).Methods:The clinicopathological materials of 45 cases of DLBCL of CNS were retrospectively collected in Xuanwu Hospital, Capital Medical University from September 2014 to February 2017. The clinicopathological data were retrospectively analyzed, combined with immunohistochemistry, EB virus in situ hybridization, imaging and medical history. The mutation of MYD88 L265P gene was detected by pyrosequencing and its clinical significance was analyzed. Results:The age of the patients ranged from 42 to 82 years [(57.6±8.8) years], including 24 males and 21 females. Totally 93.3% (42/45) of the patients had supratentorial tumours, which were single or multiple. The cerebral hemisphere (31/45, 68.9%) was the most common involved site, and 21 cases (21/45, 46.7%) had multiple lesions. Histologically, DLBCL in the CNS showed diffuse infiltration of tumor tissue, some of which grew around blood vessels in a "sleeve" arrangement. CD 20 and CD 79a were diffusely and strongly positive. Thirty-nine cases (39/45, 86.7%) were non-germinal center B cell (non-GCB) subtype and 6 cases (6/45, 13.3%) were germinal center B cell (GCB) subtype. MYD88 L265P mutation was found in 64.4% (29/45) patients. There was statistically significant difference between non-GCB type (71.8%, 28/39) and GCB type DLBCL (1/6, P=0.017). Compared with the operation/biopsy group without chemotherapy, operation+chemotherapy, biopsy+chemotherapy, operation/biopsy+chemotherapy+stem cell transplantation can improve the survival and prognosis ( HR=0.05, 95% CI 0.01-0.33 , P=0.002; HR=0.04, 95% CI 0.01-0.36 , P=0.004; HR=0.01, 95% CI 0.00-0.17 , P=0.001; respectively). Conclusions:DLBCL of the CNS is aggressive tumor with poor prognosis, the clinical manifestations are complex and diverse, and the diagnosis is challenging. MYD88 L265P is a common and specific gene mutation in primary CNS lymphoma(PCNSL), which is of great significance in the diagnosis and treatment of lymphoma. The MYD88 L265P mutation was more frequently detected in non-GCB than GCB subtype. Chemotherapy can improve the survival rate of PCNSL patients. If chemotherapy achieves complete remission and autologous hematopoietic stem cell transplantation is performed, there may be a chance of long-term survival.