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Synthetic lethality is a proven effective antitumor strategy that has attracted great attention. Large-scale screening has revealed many synthetic lethal genetic phenotypes, and relevant small-molecule drugs have also been implemented in clinical practice. Increasing evidence suggests that CDKs, constituting a kinase family predominantly involved in cell cycle control, are synthetic lethal factors when combined with certain oncogenes, such as
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Objective@#Apolipoprotein E (ApoE) is mainly synthesized in the liver. So far, it is unknown the relationship among APOE gene polymorphisms and WML, brain atrophy. Therefore, the aim of the study was to assess the associations of APOE gene polymorphisms in patients with WML and brain atrophy. @*Methods@#A total of 58 patients with WML, 128 patients with brain atrophy, 112 patients with co-occurrence of WML and brain atrophy and 95 healthy elderly volunteers were recruited from Renmin Hospital of WuHan University. @*Results@#Allele E3 was the most common allele. The alleles E2 had significantly higher levels of ApoB and lower age in WML group. The alleles E2 was associated with the lower level of ApoB, LDL-Ch, TCh, and sdLDL in co-occurrence group. The E3/E3 genotype has higher level of sdLDL, but lower age and female frequency in WML. The E3/E4 genotype had higher level of TG, but lower age in WML. Gender, Age, E2, Hyperhomocysteinemia and UA were also significantly associated with disease progression. @*Conclusion@#This study found that clinical data, lipids and metabolic complications were closely related to ApoE genotypes and alleles, and also disease progression and type.
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Objective:To analyze the risk factors of fatal outcome in patients with severe COVID-19.Methods:The clinical characteristics of 107 patients with severe COVID-19 admitted in Renmin Hospital of Wuhan University from February 12 to March 12, 2020 were retrospectively analyzed. During the hospitalization 49 patients died (fatal group) and 58 patients survived (survival group). The clinical characteristics, baseline laboratory findings were analyzed using R and Python statistical software. The risk factors of fatal outcome in patients with severe COVID-19 were analyzed with multivariate logistic regression.Results:Univariate analysis showed that the two groups had statistically significant differences in age, clinical classification, dry cough, dyspnea and laboratory test indicators ( P<0.05 or <0.01). The random forest model was used to rank the significance of the statistically significant variables in the univariate analysis, and the selected variables were included in the binary logistic regression model. After stepwise regression analysis, the patient’s clinical type, age, neutrophil count, and the proportion of CD3 cells are independent risk factors for death in severe COVID-19 patients. Dry cough is an independent protective factor for the death of severe COVID-19 patients. Conclusion:COVID-19 patients with fatal outcome are more likely to have suppressed immune function, secondary infection and inflammatory factor storm. These factors may work together in severe patients, leading to intractable hypoxemia and multiple organ dysfunction and resulting in fatal outcome of patients. The study indicates that timely intervention and treatment measures against above factors may be effective to save the lives of patients with severe COVID-19.
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Objective:To understand the implementation of learning mode of "College in Hospital", and ex-plore the new ideas of vocational education, in order to provide reference basis for enriching talent training mode. Method:Since the fourth semester of February 2016 , nursing specialty of Shandong Medical College sent nursing students to cooperation hospital for the study of nursing professional courses, including hospital classroom learning and beside study of clinical department. It adopted the way of classroom learning in the morning and clinical clerk-ship in the afternoon, and achieved that theoretical learning and clinical operation were seamlessly linked, the two sides jointly constructed a teaching plan, the teaching process was interconnected timely, evaluation methods was innovated and process evaluation and summative assessment modes were adopted. Result: The"College in Hospi-tal" learning mode was conducive to the improvement of nursing students' learning efficiency, and really achieved professional and industry, occupation post docking, professional courses and professional standard docking, the teaching process and the production process docking, academic certificate and occupation qualification certificate docking and vocational education and lifelong learning docking. Conclusion:The learning mode has achieved re-markable results, with demonstration and promotion value.
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Background:Gastric cancer is a common gastrointestinal malignancy. The detection rate of early gastric cancer is still low in China,and some gastric cancer patients visit the hospital due to acute disease,such as gastric perforation. Aims:To investigate the influence of acute disease on long-term prognosis in gastric cancer patients. Methods:A total of 318 patients with gastric cancer from Jan. 2009 to Jan. 2015 at Shaoxing People’s Hospital were enrolled,and were divided into acute disease group and non-acute disease group. Clinicopathological characteristics were analyzed. Patients were followed up,and survival rate was compared between the two groups. Results:Fifty-three(16. 7% )patients had acute disease,and the remaining 265(83. 3% )patients were without acute disease. Compared with non-acute disease group, percentage of TNM Ⅳ stage was significantly increased(P < 0. 05),and percentage of radical surgery was significantly decreased in acute disease group(P < 0. 05). Kaplan-Meier assay showed that survival rate in acute disease group was significantly decreased when compared with non-acute disease group( P < 0. 05). After adjusting the TNM stage and surgical treatment,no significant difference in survival rate was found between the two groups. Conclusions:Gastric cancer patients with acute disease have lower survival rate. Acute disease may be not an independent prognostic factor, higher TNM stage and lower proportion of radical surgery are the main reasons for poor prognosis in gastric cancer patients with acute disease.
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Objective To report the early mortality and associated risk factors after damage control operation (DCO) in patients with severe abdominal trauma.Methods A total of 146 patients hospitalized from January to March in 2015 were retrospectively analyzed.Early death was defined as death occurring within 72 h of first surgery and before the definitive surgery.Based on the death definition, the subjects were divided into death group and survival group.The two groups were compared for gender, age, injury time, injury classification, vital signs, need for cardiopulmonary resuscitation, Glasgow coma score (GCS), injury severity score (ISS), hemoglobin, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), blood pH, base excess, operative time, and postoperative acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ).Logistic regression analysis was applied to examine the predicators of early postoperative mortality.Results There were 118 patients (80.8％) in survival group and 28 patients (19.2％) in death group.Survival and death groups differed significantly with regard to the percent of elderly (6.8％ vs.21.4％), percent of patients with multiple injury (62.7％ vs.85.7％), body temperature [(36.1 ± 0.4) vs.(35.2 ± 0.8) ℃], percent of patients with greater ISS (31.4％ vs.64.3％), PT [(12.1±1.5) vs.(13.9±1.2)s], bloodpH (7.25±0.04vs.7.08±0.11), base excess [(-8.9±2.8) vs.(-10.6±3.3)mmol/L], postoperative APACHE Ⅱ[(12.8 ± 1.8) vs.(17.5 ± 2.0) points] (P ＜ 0.05).Logistic regression analysis identified the age (OR=1.512, 95％ CI 1.112-4.157,P＜0.05), ISS (OR =1.313,95％ CI 1.134-5.442, P ＜ 0.05), APACHE Ⅱ (OR =1.361,95 ％ CI 1.182-5.222, P ＜ 0.05) as the independent risk factors for early mortality.Conclusion The patients underwent DCO for severe abdominal trauma has a high early mortality, which is closely associated with the age, injury severity and postoperative medical status.
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Objective To evaluate the clinical application of liver shear wave velocity (SWV) in comparison with common serum score systems [AST to platelet ratio index (APRI),Forns,S index and FIB-4] in assessment of liver fibrosis in patients with chronic hepatitis.Methods A total of 237 chronic hepatitis patients with liver fibrosis confirmed by liver biopsy,who were admitted in Ningbo Second Hospital during October 2010 and April 2013,were enrolled in the study.Liver shear wave velocity were measured by acoustic radiation force impulse (ARFI),and the score of APRI,Forns,S index and FIB-4 were calculated based on the measurement of serum markers.Liver fibrosis stages were classified as S0-S4 according to the Scheuer scoring system,and stages ≥ S2 were identified as significant liver fibrosis.The diagnosis value of SWV,4 common score systems and their combination for significant liver fibrosis was evaluated by receiver operating characteristic curve (ROC).Results A significant linear correlation was found between SWV and the stage of fibrosis (r =0.46,P ＜ 0.01).The areas under the ROCs of SWV and 4 common score systems (APRI,Forns,S index and FIB-4) for the diagnosis of significant liver fibrosis were 0.758 (0.696-0.821),0.727 (0.662-0.793),0.777 (0.717-0.836),0.747 (0.684-0.810) and 0.737 (0.673-0.802),respectively.The area under the ROC of the combined prediction nodel established with Logistic regression was 0.810.Conclusion Liver shear wave velocity measured by ARFI is of clinical value in noninvasive assessment of liver fibrosis,and the prediction accuracy can be improved when it is combined with other noninvasive indices.
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Objective To analyze the association of the single nucleotide polymorphism (SNP) of Toll-like receptor 7 (TLR7) and Toll-like receptor 9 (TLR9) with chronic hepatitis C virus (HCV)infection.Methods A total of 150 patients with chronic hepatitis C (CHC) admitted to Renmin Hospital of Wuhan University from January 2011 to May 2012 and 168 healthy controls were enrolled in the study.The genotypes of TLR7 IVS2-151 (rs179009) were detected by Sanger sequencing,and the genotypes of TLR9 T-1486C (rs187084) were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).SPSS 15.0 was used for statistical analysis,and goodness-of-fit test for HardyWeinberg equilibrium was also performed.Results The frequency of TLR7 IVS2-151G was higher in malepatients with CHC than that in male controls (41.4％ vs.21.6％,x2 =7.250,P =0.007,OR =0.389,95％ CI:0.194-0.781) ; however the female CHC patients had a higher frequency of TLR7 IVS2-151A than the female controls (76.9％ vs.63.1％,x2 =7.202,P =0.007,OR =1.942,95％ CI:1.192-3.164).No significant difference in the distribution of TLR9 T-1486C (rs187084) gene SNP was observed betweenCHC and control groups (P ＞0.05).Conclusion TLR7 IVS2-151 (rs179009) is correlated with HCV infection,which may be involved in the pathogenesis of CHC.
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Objective To explore the effect of hepatitis B virus(HBV) on the expression of apolipoprotein A1 (ApoA1) and its regulatory mechanism.Methods RT-PCR and Western blot were used to measure the expression of ApoA1 in HepG2 and HepG2.2.15 cells,serum ApoA1 and high density lipoprotein cholesterol(HDL-C) levels in patients with HBV infection and in healthy individuals were measured by biochemical analyzer,statistical difference was analyzed by SPSS13.0,HepG2 cells was co-transfected with ApoA1 promoter containing the luciferase gene and HBV infectious clone pHBV1.3,luciferase activity was measured,expression of ApoA1 in HepG2 cells was measured by RT-PCR and Western blot after transfected with pHBV1.3.Results Expression of ApoA1 mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells,serum ApoA1 and HDL-C levels were much lower in HBV patients as compared to healthy individuals( P＜0.05 ),HBV represses ApoA1 gene promoter activity,ApoA1 mRNA and protein expression in HepG2 cells.Conclusion HBV can inhibit the expression of ApoA1 bothin vivo and in vitro.
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Objective To investigate the differences of kinesin family member 4 (KIF4A) expression between hepatic carcinoma and adjacent tissue in patients with chronic hepatitis B virus (HBV) infection,and to understand the effect of HBV on the expression of KIF4A.Methods Reverse transcriptase-polymerase chain reaction and Western blot were used to measure the expression of KIF4A in hepatic carcinoma and adjacent tissues. HepG2 cells were co-transfected with KIF4A promoter containing the luciferase gene and HBV infectious clone pHBV1.3,and luciferase activity was measured.Expression of KIF4A in HepG2 cells was measured after tranfected with different doses of pHBV1.3.The student's t-test was used for statistic analysis.Results Expression of KIF4A was much higher in hepatic carcinoma than that in adjacent tissues.HBV enhanced KIF4 A gene promoter activity and the luciferase activities were increased as the concentration of pHBV1.3 increased ( 0,0.2,0.4,0.6 and0.8 μg/mL),which were (126.8± 13.4),(219.8±16.7),(387.6±21.5),(586.5 ± 228.9 ) and (657.6 ± 35.5 ) RUL/μg protein,respectively,while the luciferase activities were (123.6± 13.8),(131.8± 14.6),(129.7-13.5),(135.3± 13.4) and (127.1± 12.7) RUL/μg protein,respectively with different doses of control plasmids transfected,and statistical analysis showed significant difference between them (t=4.875,P=0.006).And HBV upregulated KIF4A mRNA and protein expressions in HepG2 cells in a concentration-dependent manner.Conclusion Expression of KIF4A is enhanced in hepatic carcinoma and HBV can upregulate KIF4A expression.
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Objective To explore the effect of hepatitis B virus(HBV) on the expression of complement 3 (C3) and complement 4 (C4) and its regulatory mechanism.Methods Differentially expressed genes between HepG2 and HepG2.2.15 cells was screened by gene chip,serum complement component 3 (C3) and 4 (C4) levels in patients with HBV infection and in healthy individuals were measured by Immunoturbidimetry,HBV infectious clone pHBV1.3 was transfected into HepG2 cells,and expression of C3 and C4 was measured by RT-PCR and Western blot.Results Expression of C3 and C4 mRNA was lower in HepG2.2.15 cells than in HepG2 cells,serum C3 and C4 levels was much lower in patients with chronic hepatitis B and hepatic carcinoma as compared to healthy individuals (P＜0.05 ).HBV could downregulate the expression of C3 and C4 at mRNA and protein levels.Conclusion HBV may inhibit the expression both in vivo and in vitro.
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Objective To explore the effect of hepatitis B virus(HBV) on the expression of apolipoprotein B(ApoB) and its regulatory mechanism. Methods mRNA and protein expression of ApoB in HepG2 and HepG2.2.15 cells was measured by RT-PCR and Western blot, serum ApoB levels in patients with HBV infection and in healthy individuals were measured by biochemical analyzer Olympus 5400, the expression of ApoB difference among healthy individuals, patients with chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma were analyzed, HBV infectious clone pHBV1.3 was tranfected into HepG2 cells,and expression of ApoB and microsomal triglyceride transfer protein(MTP) was measured by RT-PCR and Western blot. Results Expression of ApoB mRNA and protein was lower in HepG2.2.15 cells than in HepG2 cells, serum apoB levels was much lower in patients with chronic hepatitis B and liver cirrhosis as compared to healthy individuals( P ＜0.05 ), HBV could inhibit the expression of ApoB and MTP at mRNA and protein levels. Conclusion HBV may downregulate the synthesis and secretion of ApoB via inhibits the expression of MTP.
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Objective To investigate the effect of nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) on the expression of cyclooxygenase-2 (COX-2). Methods 293T cells were co-transfected with reporter plasmid pCOX-2-Luc containing the luciferase gene under the control of COX-2 promoter and plasmids carrying individual genes of SARS-CoV, and luciferase activity was measured. Expression of COX-2 mRNA and protein was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Results N protein of SARS-CoV enhanced COX-2 gene promoter activity, and upregulated COX-2 mRNA expression.COX-2 protein production in 293T cells was N protein concentration-dependent. Conclusion N protein of SARS-CoV could specifically activate COX-2 expression.
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Objective To explore the regulatory effect of LPS on the expression of interleukin 27 (IL-27),and uncover the relationships among cyclooxyenase-2(COX-2),prostaglandin E2(PGE2) and IL-27.Methods THP-1 cells were stimulated with different doses of LPS,IL-27 and PGE2 levels in the supernatants were measured by enzyme-linked immunosorbent assay(ELISA) at different time,expression of COX-2 was measured by RT-PCR and Western blot.Results IL-27 can be induced by LPS in THP-1 cells in a time and dose dependent fashion,and IL-27 induces COX-2 mRNA expression,COX-2 protein production,and PGE2 release in a time and dose fashion.Conclusion LPS can stimulate the relase of IL-27 at cell level,and IL-27 can induce the expression of COX-2 and production of PGE2.