Objective To study the clinical characteristics of septicemia and septic shock in elderly patients with liver disease. Methods Fifty-two patients over 60 years old with liver disease and positive blood culture, admitted form 1999 to 2003, were enrolled for analysis. Results Septic shock was found in 8 patients (15.4%). The course of sepsis was complicated by progressive deterioration of hepatic and renal functions. 18 patients (34.6%) died or left the hospital in a critical condition. 52 strains of pathogenic bacteria were isolated, among which 71.2% were G +germ, 26.9% G -germ and 1.9% fungi. Conclusion Septicemia and septic shock can exacerbate liver disease. Early diagnosis and treatment should be emphasized to lower the mortality.

Objective To investigate the expressions of epidermal growth factor receptor (EGFR),heat shock protein 90A (HSP90A) and cathepsin D in nasopharyngeal carcinoma and their relationship with tumor invasion and metastasis.Methods From January 2014 to December 2015,58 patients with nasopharyngeal carcinoma (group A) in the First Affiliated Hospital of University of South China were selected,and the positive expression rates of EGFR,HSP90A and cathepsin D in biopsy specimens of nasopharyngeal carcinoma were detected by immunohistochemistry method.The positive expression rates of EGFR,HSP90A and cathepsin D in biopsy chronic rhinitis tissues of 30 patients with chronic rhinitis (group B) were also detected.T staging,N staging and lymphatic vessel density (LVD) of patients in group A were analyzed.In group A,the T staging,N staging and LVD of between patients with positive expression of EGFR,HSP90A and eathepsin D and those with negative expression of these indicators were compared,and the correlations of the expression of EGFR,HSP90A and cathepsin D to T staging,N staging and LVD were analyzed.Results The positive expression rates of EGFR,HSP90A and cathepsin D in group A were 86.21％,82.76％ and 87.93％ respectively,which were higher than 30.00％,26.67％ and 33.33％ in group B (P＜0.05).In group A,the percentages of patients on T3-T4 and N2-N3 stages and LVD of patients with positive expression of EGFR,HSP90A and cathepsin D protein respectively were higher than those of patients with negative expression of corresponding protein (P ＜ 0.05).Spearman correlation analysis showed that the positive expression rates of EGFR,HSP90A and cathepsin D in nasopharyngeal carcinoma were positively correlated with the T staging,N staging and LVD (EGFR:r=0.844,0.795,0.785;HSP90A:r=0.862,0.825,0.822;eathepsin D:r=0.842,0.815,0.863,P＜0.05).Conclusion EGFR,HSP90A and cathepsin D expression in nasopharyngeal carcinoma are closely related to invasion and metastasis of tumor,which may be used as reference indexes for the evaluation of tumor invasion and metastasis in nasopharyngeal carcinoma.

Objective:To systematically review the severe risk in common chronic diseases and coronavirus disease 2019 (COVID-19) cases.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, medRxiv, SSRN and ChinaXiv were searched for clinical and epidemiological studies that reported chronic diseases in patients with COVID-19. Only studies of severe COVID-19 in comparison with non-severe controls were included. The prevalence rates of chronic diseases including chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, malignant tumor, cardiovascular diseases, cerebrovascular disease, chronic kidney disease, and chronic liver disease were estimated. Pooled odds ratio ( OR) with 95% confidence interval ( CI) between patients with severe COVID-19 and non-severe groups were calculated. R 3.6.3 software was used for meta-analysis. Results:The search yielded 2 455 articles. A total of 19 eligible comparative studies with 4 792 patients were included in a quantitative analysis. Meta-analysis showed that there was a proportion of 55.0% (95% CI 40.0%-80.0%) male among patients with COVID-19, and the overall pooled prevalence of any chronic diseases in COVID-19 cases was 30.4% (95% CI 24.0%-37.0%). The most prevalent comorbidity was hypertension (16.9%(95% CI 14.0%-20.0%)), followed by diabetes mellitus (8.3%(95% CI 8.0%-9.0%)). The proportion of male patients with severe COVID-19 was higher than that of male patients with non-severe COVID-19 (64.4% vs 52.8%, OR=1.49, 95% CI 1.08-2.05, Z=4.63, P<0.01). The prevalence rates of COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor in severe COVID-19 patients were higher than those of non-severe patients ( OR=5.77, 95% CI 3.80-8.74; OR=4.47, 95% CI 2.71-7.38; OR=3.55, 95% CI 2.86-4.40; OR=3.05, 95% CI=1.76-5.28; OR=2.82, 95% CI=1.96-3.97; OR=2.39, 95% CI=1.77-3.23; OR=2.15, 95% CI 1.27-3.66, respectively, Z=8.37, 6.01, 11.60, 4.20, 5.46, 5.71, 3.12, all P<0.01). There was no significant difference in the prevalence of chronic liver disease between severe and non-severe patients ( OR=1.35, 95% CI 0.84-2.17, P=0.11). Conclusion:COVID-19 patients with chronic diseases have higher risk of developing severe disease, and the ORs from high to low are COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor.

Objective:To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods:98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results:During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log 10IU/ml vs. (0.73 ± 0.81) log 10IU/ml, P = 0.017; (1.54 ± 1.27) log 10IU/ml vs. (0.57 ± 0.56) log 10IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion:Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

Objective To observe the effect of HIF-1a/iNOS signaling pathway on myocardial ischemia-reperfusion injury in rat heart transplantation and the protective mechanism of N-acetylcysteine (NAC) on donor heart after cardiac transplantation in rats.Methods Eighty healthy male Lewis rats were randomly divided into 3 groups,the control group (0.3 ml saline was infused via inferior vena cava 30 min before donor harvest or implantation),NAC donor pretreatment group [NAC (30 mg/kg.w) was injected into the vena cava of donor rat 30 min defore donor harvest],and the NAC receptor pretreatment group (NAC 300 mg/kg.w was injected into the vena cava of the recipient rats 30 min before transplantation.The 30 min was injected into the vena cava of the recipient rats).A transplant model was established and the graft was obtained after 24 h transplantation.The expression of iNOS,HIF-1a and mRNA in cardiac muscle tissue was detected by immunohistochemistry and Real time-PCR.Results HIF-1a protein expression in graft myocardial tissue was significantly lower in NAC donor pretreatment and recipient pretreatment group compared with control group (P ＜0.05),the differences were statistically significant (2.72±0.17 vs.2.24±0.23 vs.3.14.±0.16,F=56.26,P =0.000).The iNOS protein expression in NAC donor pretreatment group,and NAC recipient pretreatment group were lower than that in the control group (1.52±0.18 vs.1.61±0.19 vs.3.30±0.18,F=232.345,P =0.000),the differences were statistically significant (P ＜ 0.05).24 h after transplantation,the differences in graft myocardial tissue HIF-1a and iNOS mRNA among the three groups were statistically significant (F=7.467,16.490,P=0.003,0.000).The expression of iNOS mRNA in the NAC receptor pretreatment group was significantly lower than that in the control group (P＜0.05).Conclusion HIF-1a/iNOS signaling pathway can regulate ischemia reperfusion injury in rat heart transplantation,and the protective effect of NAC on donor heart maybe mediated via this pathway.

Objective:To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB).Methods:144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ2 test between groups. Results:41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline ( OR = 0.090, 95% CI: 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level ( OR = 7.788, 95% CI: 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI: 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95% CI: 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two ( Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95% CI: 0.941-0.997) was superior to that of single baseline HBsAg quantification ( Z = 3.017, P = 0.003) and 24-week drop in HBsAg level ( Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks ( HR = 0.364, 95% CI: 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion:The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment.

Objective: To investigate the effects of artesunate combined with bortezomib on the proliferation, apoptosis and autophagy of human acute myeloid leukemia cell lines MV4-11, and its mechanisms. Methods: MTT method was used to determine the anti-proliferation effect of different concentrations of artesunate, bortezomib and their combination on MV4-11 cells. The cell apoptosis were analyzed by flow cytometry. The expression of cleaved-Caspase-3, Bcl-2 family protein (Bcl-2, Mcl-1, Bim, Bax) and autophagy-related protein LC3B were assayed by Western blot. Results: Artesunate displayed a proliferation inhibition effect on MV4-11 with dose- and time-dependent manner, the IC₅₀ of artesunate on MV4-11 after 48 hours was 1.44 μg/ml. Bortezomib displayed a proliferation inhibition effect on MV4-11 with dose-dependent manner, the IC₅₀ of bortezomib on MV4-11 after 48 hours was 8.97 nmol/L. The combination of artesunate (0.75, 1.0 μg/ml) and Bortezomib (6, 8 nmol/L) showed higher inhibition on MV4-11 than artesunate or bortezomib alone in the same concentration gradient after 48 hours (P<0.05) . The cooperation index of the two drugs were all less than 1. The 48 h apoptotic rate of artesunate (1.5 μg/ml) on MV4-11 was (15.27±2.18) %, (19.85±3.23) % of bortezomib (8 nmol/L) , (81.67±5.96) % of combination of the two drugs, significantly higher than the single group (P<0.05) . When combination of the two drugs on MV4-11 after 24 hours, the levels of pro-apoptotic protein Bim and the cleaved activation of Caspase-3 and autophagy-related protein LC3B were up-regulated and the anti-apoptotic protein Bcl-2 expressions was down-regulated. Conclusion Combination of artesunate with bortezomib shows a significant synergistic effects on proliferation, apoptosis and autophagy of MV4-11 cell lines, which may be associated with Bcl-2 family proteins expression.

Objective: To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C. Methods: Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded. Results: 108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin. Conclusion Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.