Objective To evaluate the clinical efficacy of low molecular weight heparin in treatment of patients with severe community-acquired pneumonia (CAP).Methods PubMed, BMA, EMbase, ASP, Cochrane Library, EMCC, CBM, CNKI, CECDB, CQVIP, and VIP databases were searched to identify the relevant randomized clinical trials (RCTs) from the publications during the period from January 1994 to January 2014. The search terms were “low molecular heparin”, “severe community-acquired pneumonia”, “prognosis” in both Chinese and English. The quality of the included studies were strictly evaluated and data were extracted. Stata/SE version 12 software was used for systematic review and meta-analysis.Results Six RCTs were ifnally qualiifed in the analysis, including a total of 208 cases in treatment group and 196 cases in control group. The patients in control group received conventional therapy, while the patients in treatment group received low molecular weight heparin by subcutaneous injection as add-on to conventional therapy. Meta-analysis showed that after treatment with low molecular weight heparin for 7 days, the APACHE II score of severe CAP patients signiifcantly decreased (P = 0.43,I2 = 0%, SMD = -0.70, 95%CI: - 0.90, -0.49) with controllable publication bias (bias_p = 0.93, bias_95CI: -6.79, 6.37). The PaO2 of severe CAP patients signiifcantly increased (P = 0.858,I2 =0%, SMD = 0.51, 95%CI: 0.30, 0.72) with controllable publication bias (bias_p =0.770, bias_95CI: -4.82, 5.90). However, after low molecular weight heparin treatment for 7 days, the PaCO2 of severe CAP patients did not change significantly (SMD = -0.17, 95 %CI: -0.38, 0.04).Conclusion Low molecular
weight heparin is beneifcial in the treatment of severe CAP patients in terms of signiifcantly decreased APACHE II score, increased oxygenation, and improved clinical symptoms.

Objective To explore the effect of hesperidin on cardiac function and ventricular remodeling following myocardial infarction (MI) in mice.Methods Ligation of left anterior descending (LAD) was operated to establish MI model.Forty-two C57BL/6 mice were randomly (random number) divided into control and MI group;and 24 h after LAD ligation,mice in MI group were further divided into MI control and hesperetin group.Eight weeks later,cardiac function and structure changes were determined by the methods of hemodynamic measurement and echocardiography.HE staining was used to measure crosssectional area (CSA) of atrial myocytes,and PSR staining was applied for observe collagen deposition and calculation of collagen volume fraction (CVF).Real-time PCR was used to detect the mRNA expressions of cardiac hypertrophy markers (ANP,BNP and β-MHC) and cardiac fibrosis markers (Collagen Ⅰ,Collagen Ⅲ and CTGF).The contents of superoxide anion and hydroxy radical were detected by colorimetric method.Results Compared with control group,left ventricular posterior wall thickness (LVPWT) and interventricular septum thickness (IVST) were increased to be thicker,left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly lower,and ± dp/dtmax was remarkably reduced in MI control group (P ＜ 0.05).Compared with MI control group,hesperetin could increaseLVFS [(29.48±3.87)％ vs.(20.69±3.99) ％],LVEF [(46.40±1.68)％ vs.(30.51± 1.17) ％] and ±dp/dtmax [(3 344.33 ±269.57) mmHg/S vs.(2 205.19 ±224.17) mmHg/S;(2250.40±218.35) mmHg/S vs.(-1 566.91 ±217.37) mmHg/S];but could reduce LVPWT [(2.29±0.05) mm vs.(2.85±0.10)mm]andIVST[(1.44±0.09) mm vs.(1.89±0.06) mm].Compared with control group,CSA and CVF were significantly increased in MI control mice.However,hesperetin could reduce CSA and CVF.Compared with control group,the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers were significantly increased in MI control mice;but hesperetin could significantly inhibit the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers.Additionally,hesperetin could significantly reduce the contents of superoxide anion and hydroxy radical.Conclusion Hesperetin intervention can inhibit ventricular structure change,and improve hemodynamics and cardiac function after acute myocardial infarction via inhibiting the production of reactive oxygen species (ROS).

Objective:To evaluate the effects of comprehensive reform of clinical education on cultivating the clinical thinking ability of medical students in internal medicine.Methods:A total of 44 clinical interns on medicine rotation were included in this study and divided into experimental group and control group, and a series of measures for clinical teaching reform, which included undergraduate tutorial system, team-based learning (TBL) mode, combination of electronic medical record and handwritten medical record, as well as formative assessment, were applied to fully promote clinical thinking ability of medical students. SPSS 17.0 software was used to compare the scores of final academic tests of rotation and competition of medical record writing between the control and the experiment groups. Self-designed questionnaires on undergraduate tutors and clinical interns were applied to comprehensively evaluate the effects of this education reform.Results:Independent-sample t tests showed there were statistically significant difference ( P<0.01) in the scores of final academic tests of rotation and competition of medical record writing between the two groups, and the mean score of the experiment group was higher than that of the control group. Questionnaire survey showed that tutors and clinical interns both fully affirmed the positive effects of the education reform on cultivating clinical thinking ability of medical students in internal medicine. Conclusion:Application of comprehensive education reform in clinical teaching of internal medicine, which based on introduction of undergraduate tutorial system and TBL mode, could effectively promote the clinical thinking ability of medical students and the teaching quality.

Purpose To investigate the effect and molecu-lar mechanism underlying SOX9 during esophageal squamous cell carcinoma(ESCC)cells.Methods Immunohistochemistry(IHC)was used to detect the expression of SOX9 in ESCC tis-sues and adjacent normal tissues.The correlation of SOX9 ex-pression with clinicopathological features and prognosis of ESCC was analyzed.The differentially expressed genes in Eca109-Vec-tor and Eca109-SOX9 cells were detected by Affymetrix miRNA array.qRT-PCR was used to determine the differential gene in TE-1 and TE-1-siSOX9 cells.The relationship between SOX9 and active/unphosphorylated β-catenin levels was detected by Western blot.The effects of Wnt inhibitor LGK974 on the prolif-eration of ESCC cells were detected by CCK-8.Results SOX9 was highly expressed in ESCC(4.58±3.04)as compared with that in adjacent normal tissues(1.56±2.08,P＜0.001).SOX9 was related to histopathological grade and invasion depth(P＜0.05).Kaplan-Meier analysis indicated high SOX9 expres-sion in ESCC was significantly correlated with shorter overall sur-vival(P＜0.05).Transcriptome profiling and qRT-PCR analysis suggested that SOX9 contributed to the regulation of AXIN2,FZD7 and WNT5A.Overexpression of SOX9 in Eca109 cells in-creased active/unphosphorylated β-catenin levels,whereas silen-cing SOX9 caused a decrease.Significant attenuation of cell pro-liferation was observed at various concentrations of LGK974 with-out affecting SOX9 expression on SOX9-expressing cell lines.As expected,this inhibitory effect was not obvious in Eca109-Vector cells when compared with Eca109-SOX9 cells treated with the same concentration of LGK974.Conclusion SOX9 is highly ex-pressed in ESCC and SOX9-mediated Wnt/β-catenin signal path-way activation at least partially contributes to the SOX9-induced ESCC growth.These findings suggest that SOX9 is a promising prognostic marker and therapeutic target for ESCC.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective:To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15(Siglec15)derived from M2 tumor-associated macrophages(M2-TAMs)on promoting the malignant biological behavior of the esophageal squamous cell carcinoma(ESCC)through bioinformatics analysis,and to validate the findings through cell experiment.Methods:The Tumor Immune Estimation Resource(TIMER)online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells.Based on the non-contact co-culture of M2-TAMs and ESCC cells,the following groups were set up,such as EC109/KYSE150 group,EC109/KYSE150+si-NC group(transfected with si-NC sequence),and EC109/KYSE150+si-Siglec15 group(transfected with si-Siglec15#1 and si-Siglec15#2 sequences).CCK-8 method was used to detect the proliferation activities of the cells in various groups;wound healing assay was used to detect the wound healing rates of the cells in various groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal tissue,the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer,colon cancer,and head and neck squamous cell carcinoma tissues were increased(P＜0.05 or P＜0.01),and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages(P＜0.05).Compared with the EC109 cells and KYSE150 cells,the expression level of Siglec15 mRNA in M2-TAMs was significantly increased(P＜0.01).There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group,EC109/KYSE150+si-NC group,and EC109/KYSE150+si-Siglec15 group(P＞0.05).Compared with EC109/KYSE150 group,after treated for 24 and 48 h,the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased(P＜0.01),the numbers of migration and invasion cells were increased(P＜0.05),and the apoptotic rate was decreased(P＜0.01).Compared with EC109/KYSE150+si-NC group,the wound healing rates of the cells in EC109/KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased(P＜0.05),the numbers of migration and invasion cells were decreased(P＜0.05),and the apoptotic rates of the cells had no significant difference(P＞0.05).Conclusion:Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells.