Hypoxia and inflammation are risk factors for acute myocardial injury in patients with coronavirus disease 2019 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the risk factors for acute myocardial injury in coronavirus disease 2019 (COVID-19) patients.@*METHODS@#This is a retrospective analysis of a COVID-19 cohort, in which 149 confirmed COVID-19 patients enrolled were divided into the group of myocardial injury (19 cases) and the group of non-myocardial injury (130 cases). Myocardial injury was defined according to Fourth universal definition of myocardial infarction released by European Society of Cardiology (ESC) in 2018, that cardiac troponin (cTn) was above 99th percentile of the reference level. Clinical information and results of laboratory tests of the eligible patients were collected. Factors associated with myocardial injury in COVID-19 patients were evaluated.@*RESULTS@#Compared with the group of non-injury, the patients in the group of injury were older and had a larger proportion of severe or critical cases (P < 0.05), higher respiratory rate and lower percutaneous oxygen saturation (SpO2) without oxygen therapy on admission (P < 0.05). All inflammatory indexes except for tumor necrosis factor α (TNF-α) showed significant elevation in the patients of the group of injury (P < 0.05). Analyzed by Spearman correlation test, we showed that the levels of circulatory cTnI were in positive correlation with the levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, receptor of interleukin-2 (IL-2R), interleukin-6 (IL-6) and interleukin-8 (IL-8) (ρ > 0, P < 0.05). Lower SpO2 without oxygen therapy on admission (OR: 0.860, 95%CI: 0.779-0.949, P=0.003) and higher plasma IL-6 levels (OR: 1.068, 95%CI: 1.019-1.120, P=0.006) were independent risk factors for acute myocardial injury in the patients with COVID-19 by multivariate Logistic regression analyses.@*CONCLUSION@#Hypoxic state and inflammation may play a key role in the pathogenesis of acute myocardial injury in COVID-19 patients.

Risks factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes / 北京大学学报(医学版)

OBJECTIVE@#The pathogenesis of myocardial injury upon corona virus disease 2019 (COVID-19) infection remain unknown,evidence of impact on outcome is insufficient, therefore, we aim to investigate the risk factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes in this study.@*METHODS@#This was a single-centered, retrospective, observational study. Patients of Sino-French Eco-City section of Tongji Hospital, Wuhan, China attended by Peking University Supporting Medical Team and admitted from Jan. 29, 2020 to Mar. 20, 2020 were included. The positive nucleic acid of COVID-19 virus and combination with hypertension, coronary heart disease or diabetes were in the standard. We collected the clinical data and laboratory examination results of the eligible patients to evaluate the related factors of death.@*RESULTS@#In the study, 94 COVID-19 patients enrolled were divided into the group of death (13 cases) and the group of survivors (81 cases), the average age was 66.7 years. Compared with the survival group, the death group had faster basal heart rate(103.2 beats/min vs. 88.4 beats /min, P=0.004), shortness of breath(29.0 beats /min vs. 20.0 beats /min, P<0.001), higher neutrophil count(9.2×109/L vs. 3.8×109/L, P<0.001), lower lymphocyte count(0.5×109/L vs. 1.1×109/L, P<0.001), creatine kinase MB(CK-MB, 3.2 μg/L vs. 0.8 μg/L, P<0.001), high sensitivity cardiac troponin Ⅰ(hs-cTnⅠ, 217.2 ng/L vs. 4.9 ng/L, P<0.001), N-terminal pro brain natriuretic peptide(NT-proBNP; 945.0 μg/L vs. 154.0 μg/L, P<0.001), inflammatory factor ferritin(770.2 μg/L vs. 622.8 μg/L , P=0.050), interleukin-2 recepter(IL-2R, 1 586.0 U/mL vs. 694.0 U/mL, P<0.001), interleukin-6(IL-6, 82.3 ng/L vs. 13.0 ng/L, P<0.001), interleukin-10(IL-10, 9.8 ng/L vs. 5.0 ng/L, P<0.001)were higher than those in the survival group. Univariate logistic regression analysis showed that the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, abnormal increase of IL 2R, IL-6, and IL-10. Multivariate regression showed that old age (OR=1.11, 95%CI=1.03-1.19, P=0.026), low non oxygen saturation(OR=0.85, 95%CI=0.72-0.99, P=0.041), and abnormal increase of IL-10(＞9.1 ng/L, OR=101.93, 95%CI=4.74-2190.71, P=0.003)were independent risk factors for COVID-19 patients combined with hypertension, coronary heart disease or diabetes.@*CONCLUSION@#In COVID-19 patients combined with hypertension, coronary heart disease or diabetes, the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, and abnormal increase of IL-2R, IL-6, and IL-10. Old age, low non oxygen saturation and abnormal increase of IL-10 were independent risk factors.

Effects of Diallyl Disulfide on the Proliferation and Apoptosis of Epithelial Ovarian Cancer Cells by Inducing G2/M Arrest / 中国医学科学院学报

Objective To explore the effects of diallyl disulfide(DADS)-induced G2/M phase arrest on proliferation and apoptosis of ovarian cancer cells and its possible molecular mechanism.Methods DADS was used to incubate SK-OV-3 and OVCAR-3 cells,respectively,in different concentrations. Cell proliferation was measured by MTT assay and cell apoptosis rate was detected by flow cytometry assay. Xenograft model assay were performed to analyze the antitumor effect in vivo. Cell cycle phase distribution was detected by flow cytometry. Expressions of cell cycle G2/M phase as well as proliferation- and apoptosis-related proteins were measured by Western blotting.Results MTT assay showed that,after treatment of SK-OV-3(F=247.86,P=0.000)and OVCAR-3 cells(F=302.54,P=0.000)with different concentrations of DADS,the cell proliferation inhibition rate was significantly elevated with the increase of DADS concentrations in a concentration-dependent manner. The inhibition rate of SK-OV-3(F=335.12,P=0.000)and OVCAR-3 cells(F=347.43,P=0.000)at 24 h was significantly higher than that at 12 h and 48 h,showing a significant time-dependence manner. Flow cytometry showed that,after SK-OV-3 and OVCAR-3 cells were treated with different concentrations of DADS,the apoptosis rates increased significantly with the increase of DADS concentration in a concentration-dependent manner(P<0.05). The apoptotic rates of SK-OV-3 and OVCAR-3 cells treated with DADS at 24 h was significantly higher than that at 12 h and 48 h in a significant time-dependence manner(P<0.05). Compared with the blank treatment group,intraperitoneal injection of DADS solution significantly inhibited the xenograft volume of ovarian cancer cells in nude mice(F=548.23,P=0.000;F=311.84,P=0.000). After 30 mg/L of DADS was applied to SK-OV-3 and OVCAR-3 cells for 24 h,the percentage of cells in G2 phase of SK-OV-3 and OVCAR-3 cells increased significantly(F=375.11,P=0.000;F=256.48,P=0.000),compared with the blank cells. After 30 mg/L DADS was applied to SK-OV-3 and OVCAR-3 cells for 24 h,the expressions of p-Chk1(ser345)(F=108.89,P=0.013;F=97.58,P=0.018),p-CDC25C(ser216)(F=87.25,P=0.025;F=114.25,P=0.009),p-P53(ser15)(F=112.41,P=0.011;F=255.87,P=0.000),P21WAF1(F=246.38,P=0.001;F=141.36,P=0.005)and p-CDK1(Thr14/Tyr15)protein(F=298.12,P=0.000;F=233.15,P=0.000)were significantly increased,whereas the expressions of CDK1(F=308.24,P=0.000;F=257.55,P=0.000)and CyclinB1 protein(F=223.15,P=0.001;F=241.28,P=0.000)were significantly reduced.The expressions of proliferation and apoptosis-related proteins PCNA(F=77.36,P=0.031;F=157.28,P=0.001),Ki-67(F=205.64,P=0.007;F=315.22,P=0.000)and Survivin(F=122.13,P=0.013;F=188.24,P=0.000)were significantly decreased and Cleaved-caspase3 protein was significantly increased(F=86.46,P=0.023;F=99.11,P=0.009).Conclusion DADS can inhibit the proliferation of ovarian cancer cells and induce their apoptosis,which may be related to the activation of Chk1-CDC25C and P53-P21WAF1 signaling pathways in G2/M checkpoint,decreased kinase activity of CDK1,down-regulated expressions of CDK1 and CyclinB1 proteins,and ultimately cell cycle arrest at G2/M phase.

Expression of metastasis-associated in colon cancer-1 in different stages of epithelial ovarian cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of metastasis-associated in colon cancer-1 (MACC1) in different International Federation of Gynecology and Obstetrics(FIGO)stages of epithelial ovarian cancer and its relationship with prognosis.</p><p><b>METHODS</b>Between May 2008 and August 2010, 52 epithelial ovarian cancer patients were selected from the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Zhengzhou University. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression of MACC1 mRNA and protein in the primary lesions of epithelial ovarian cancer patients, the levels of MACC1 in different stage patients were compared, and the relationship between expression of MACC1 and prognosis of ovarian cancer patients was analyzed by Kaplan-Meier analysis.</p><p><b>RESULTS</b>The relative expression levels of MACC1 mRNA in epithelial ovarian cancer from 1 stage to 4 stage were 0.72±0.01, 0.75±0.01, 0.78±0.01, and 0.81±0.02, respectively (F=51.305, P=0.000). The expression levels of MACC1 protein from 1 stage to 4 stage were 0.71±0.04, 0.73±0.02, 0.76±0.01, and 0.84±0.05, respectively (F=65.142, P=0.000). At the end of the follow-up, the expression of MACC1 protein in recurrence and dead patients of 3-4 stages was obviously higher than that in the patients with stable disease (0.85±0.03 vs.0.74±0.05, F=72.324, P=0.000). Compared to 1-2 stage patients with lower MACC1 expression, the survival time of 3-4 stage patients with higher MACCC1 expression was significantly shorter (χ(2)=29.804, P=0.000).</p><p><b>CONCLUSIONS</b>Increased expression of MACC1 may indicate poor prognosis of ovarian cancer patients. Therefore, MACC1 may be a potential biomarker for advanced ovarian cancer.</p>

Expressions of MACC1, HGF, and C-met protein in epithelial ovarian cancer and their significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of metastasis-associated in colon cancer-1 (MACC1), hepatocyte growth factor (HGF), and C-met proteins in epithelial ovarian cancer and their significance.</p><p><b>METHODS</b>The expressions of MACC1, HGF and C-met in 20 specimens of normal ovarian tissues, 19 specimens of benign epithelial ovarian tumor and 52 specimens of epithelial ovarian cancer were measured by immunohistochemistry and Western blotting. The correlations of the expressions of MACC1, HGF and C-met protein to the clinicopathologic characteristics of epithelial ovarian cancer were analyzed, and the correlations between the expressions of the 3 proteins were also evaluated.</p><p><b>RESULTS</b>The positivity rates of MACC1, HGF and C-met proteins were 73.1%, 63.5% and 78.8% in epithelial ovarian cancer with relative expressions of 0.72∓0.05, 0.64∓0.04 and 0.79∓0.04, respectively, showing significant differences from those in normal ovarian tissues and benign ovarian tumors (P<0.05). In epithelial ovarian cancer, the up-regulation of MACC1, HGF and C-met expressions were associated with advanced FIGO stage, poor differentiation and lymph node metastasis (P<0.05). MACC1 expression was positively correlated to HGF (r=0.350, P=0.011) and C-met expressions (r=0.429, P=0.002), and the latter two was also positively correlated (r=0.487, P=0.000).</p><p><b>CONCLUSIONS</b>MACC1 may serve as a potential biomarker for advanced ovarian cancer. Deregulation of MACC1, HGF and C-met proteins may synergistically participate in the malignant progression of epithelial ovarian cancer.</p>

Expression of TGF-beta1 and E-cadherin in primary and metastatic ovarian carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the expression of the protein of TGF-beta1 and E-cadherin in the primary and metastatic lesions of ovarian carcinoma and explore the mechanism of the metastasis of ovarian carcinoma.</p><p><b>METHODS</b>Immunohistochemistry (IHC) was performed to detect the expression of TGF-beta1 and E-cadherin proteins in primary and metastatic ovarian carcinoma, benign epithelial ovarian tumor and normal ovarian tissue.</p><p><b>RESULTS</b>The expression of TGF-beta1 was significantly higher in ovarian carcinoma (67.2%) than in benign tumors (28.6%) and normal ovarian tissue (18.9%) (Chi2=26.94, P<0.001), but E-cadherin expression showed a reverse pattern. TGF-beta1 expression in the primary ovarian carcinoma carcinoma was associated with the FIGO stage, lymph metastasis and ascites of the tumor (P=0.01, P=0.01, and P=0.04, respectively). E-cadherin expression in the tumor was associated with the differentiation (P=0.02) and lymph metastasis of ovarian carcinoma (P=0.04). The expressions of TGF-beta1 and E-cadherin were all significantly lower in the primary tumors than in the metastatic tumor (Chi2=4.70, P=0.03; Chi2=5.91, P=0.015). A significant correlation was found between the expressions of the TGF-beta1 and E-cadherin in the primary carcinoma (Kappa value of -0.32, P=0.01).</p><p><b>CONCLUSION</b>TGF-beta1 and E-cadherin are closely associated with the metastasis of ovarian carcinoma and might be potential targets for controlling the metastasis of ovarian carcinoma.</p>

VIR576 inhibits antigen-specific T cell activation by binding to the transmembrane domain of T cell receptor / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the mechanism underlying the inhibitory effect of the anti-HIV peptide VIR576 on antigen-specific T cell activation.</p><p><b>METHODS</b>CCK-8 assay was used to investigate the effect of VIR576 on the proliferation of splenocytes of OVA-specific DO11.10 Tg mice in response to chicken OVA. Hemolysis test, hemolysis inhibition assay and fluorescence binding assay were used to investigate the interaction of VIR576 with the transmembrane domain (TMD) of the T cell receptor (TCR).</p><p><b>RESULTS</b>VIR576 inhibited HIV glycoprotein gp41 fusion peptide-mediated antigen specific T cell activation, and VIR576 itself also inhibited splenocyte proliferation in responses to OVA (P<0.05). Hemolysis test, hemolysis inhibition assay and fluorescence binding assay demonstrated that VIR576 suppressed TCR-TMD-mediated hemolysis and competitively inhibited Rho-VIR576 binding to TCR-TMD peptide.</p><p><b>CONCLUSION</b>VIR576 is effective in suppressing the antigen-specific T cell activation via TCR and can interact with TCR-TMD. VIR576 may serve as a potent microbicide candidate to block sexual transmission of HIV due to of its inhibitory effect on both HIV entry and antigen-specific T cell activation.</p>