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Objective@#To investigate whether type 2 diabetes mellitus increases the risk of hepatitis B-related cirrhosis combined with type 2 diabetes mellitus for the occurrence of primary hepatocellular carcinoma, and to compare the effects of different nature of diabetes duration on the risk of different anti-diabetic drugs.@*Methods@#A retrospective case-control study was conducted. (1) 325 cases with hepatitis B-related cirrhosis complicated with primary hepatocellular carcinoma were selected as the study group and 601 patients with hepatitis B cirrhosis as the control group. The relationship between diabetes mellitus and the risk of primary liver cancer was analyzed by multivariate logistic regression analysis. (2) Selected the study group and control group combined with type 2 diabetes mellitus, and used multivariate logistic regression analysis to study the relationship between diabetes-related factors and the risk of primary liver cancer.@*Results@#The incidence of diabetes was 14.2% in the study group and 6.0% in the control group, and the difference was statistically significant between the two groups (P < 0.05). Multivariate logistic regression analysis showed that type 2 diabetes was one of the independent risk factors for primary hepatocellular carcinoma, which had increased the risk of primary hepatocellular carcinoma (adjusted odds ratio (AOR): 1.982, 95% CI: 1.224-3.210). Patients with diabetes > 10 years (adjusted ratio: AOR value 6.011, 95% CI: 1.659-21.777) were at significantly higher risk for primary hepatocellular carcinoma than that of patients with diabetes < 10 years. Metformin (adjusted odds ratio: AOR 0.188, 95% CI: 0.052-0.688) had reduced the risk, while insulin (adjusted odds ratio: AOR 6.682, 95% CI: 1.899-23.510) had increased the risk.@*Conclusion@#Type 2 diabetes mellitus is one of the independent risk factors for primary HCC, which can increase the risk of hepatocellular carcinoma in hepatitis B cirrhosis in relation to the duration of diabetes mellitus. The risk of hepatocellular carcinoma is higher in patients with duration of diabetes > 10 years and metformin reduces the risk.
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ObjectiveTo investigate the current status of compliance with antiviral therapy with nucleos(t)ide analogues (NAs) among chronic hepatitis B (CHB) patients treated in General Hospital of Ningxia Medical University. MethodsThe CHB patients who received antiviral therapy with NAs at the outpatient and inpatient services of Department of Infectious Diseases, General Hospital of Ningxia Medical University, from May to December, 2017 were enrolled. A questionnaire survey was performed for demographics, family history of CHB, detailed doctor’s advice, daily routines, physical exercise, compliance, awareness of the knowledge about hepatitis B, health belief, and social support, and the influence of various factors on compliance with NAs treatment was analyzed. The Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was used to investigate the influencing factors for compliance with antiviral therapy with NAs among CHB patients. ResultsA total of 612 questionnaires were distributed, among which 600 were collected, with a questionnaire recovery rate of 98% and a valid rate of 100%. Among the 600 CHB patients, 334 (55.67%) had good compliance with the antiviral therapy with NAs and 266 (44.33%) had poor compliance. Among the 266 CHB patients with poor compliance, 56 (21.05%) did not follow the doctor’s advice and took other drugs, 206 (77.44%) sometimes forgot medication, 187 (7030%) sometimes did not pay attention to medication (time, dose, and frequency), 135 (50.75%) reduced or stopped drugs after symptoms were improved, and 100 (37.59%) stopped the drugs due to symptom aggravation or appearance of other symptoms. The univariate analysis showed that 13 indices were the influencing factors for compliance with NAs treatment among CHB patients (all P＜0.05). A multivariate analysis was performed for these 13 indices and the results showed that race (odds ratio ［OR］=0.218, 95% confidence interval ［CI］: 0.076-0.996, P=0.007), mode of medical payment (OR=0.772, 95%CI: 0.445-0.919, P＜0.001), physical exercise (OR=2.55, 95%CI: 1.472-6.545, P=0.020), level of social support (OR=0.836, 95%CI: 0.649-0.947, P＜0.001), awareness of the outcome of incompliance (OR=0.577, 95%CI: 0.393-0.886, P＜0.001), and self-efficacy (OR=0.094, 95%CI: 0074-0.328, P＜0.001) were independent influencing factors for compliance with NAs treatment among CHB patients. ConclusionCompliance with antiviral therapy among CHB patients is closely associated with the mode of medical payment, psychological state, and self-management ability. Related measures, such as improvement of patients’ ability to pay medical expenses, education on disease risk for patients, and reduction of social discrimination, can help to improve treatment compliance.
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Objective@#Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281.@*Results@#At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss.@*Conclusion@#Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
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OBJECTIVE@#To investigate the mechanisms for inhibitory effect of aldehyde dehydrogenase 2 (ALDH2) on doxorubicin (DOX)-induced cytotoxicity in C2C12 myogenic cell line. @*METHODS@#Cell apoptosis was evaluated by flow cytometry and the activity of capase-3/7. The relative content of reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) were detected by chemical fluorometric enzyme immunoassay. The protein and mRNA expression of ALDH2, Bcl-2, NADPH oxidase 2 (NOX2) and the cytoplasmic subunit p-p47PHOX were evaluated by Western blot and quantitative PCR, respectively. @*RESULTS@#Overexpression of ALDH2 attenuated DOX-induced cell toxicity (increase in apoptosis and inhibition of proliferation), which were reversed by downregulation of ALDH2. Overexpression of ALDH2 reduced p47PHOX phosphorylation levels, and suppressed activation of NOX2 and ROS production, which were reversed by downregulation of ALDH2. Moreover, apocynin, an inhibitor of NOX, reduced the cytotoxicity of DOX concomitantly with a decrease in phosphorylation of p47PHOX, ROS production and caspase-3/7 activity, and an increase in the activity and expression of ALDH2. @*CONCLUSION@#DOX-induced cytotoxicity is related to increase of intracellular oxidative stress, which is involved in unregulation of NOX2 and downregulation of ALDH2. Activation of ALDH2 could exert cytoprotection via inhibiting NOX2-dependent ROS production.
Subject(s)
Animals , Mice , Aldehyde Dehydrogenase, Mitochondrial , Aldehydes , Apoptosis , Caspase 3 , Cell Line , Cell Survival , Down-Regulation , Doxorubicin , Oxidative Stress , Phosphorylation , Reactive Oxygen SpeciesABSTRACT
Objective To investigate the value of cytokinesis-block micronuclei(CBMN)assay in estimation of the biological doses of the victims of radiation accident.Methods Samples of peripheral blood were collected from the 5 victims(Subjects 1-5)at 16 h after the radiation accident of Taiyuan,Shanxi Province.And the peripheral blood samples and bone marrow sample were collected from the victim No.1 at 23 and 24 h after the radiation.Eight days after the accident Subject 1 underwent allogeneic peripheral blood hematopoietic stem cell transplantation.At difierent time points in the period of 1 year after the accident.peripheral blood samples were collected from these 5 victims.CBMN assay was conducted on the peripheral blood lymphocytes on the samples,and the biological doses were estimated based on the micronuclei(MN)frequencies.The nuclear division index(NDI)obtained from in vitro irradiation experiment using high dose of 60Coγ-rays was used to estimate the exposed doses for Subject 1. Dynamic arialysis of the MN frequency for the 5 victims was performed in the period of 1 year after the accident.Results The MN frequency of Subject 1 surpassed the value corresponding to the upper limit of the MN dose.effective curve.The dose range estimated bv the combination of the CBMN and NDI (CBMN+NDl)assay was 10-20 Gy for Subject 1.The doses estimated by MN frequency for Subjects 2,3,4,and 5 were 3.6,2.9,2.3,and 2.9 Gy,respectively.The estimated doses were in accordance with those estimated by physicat method.chromosome aberration analysis.and clinical symptoms.Prominent decrease of the MN frequency was observed at 26 d after the accident(18 d after the transplantation)for Subject 1(u=3.295,P<0.05).Gradual decrease of MN frequency was observed after the accident for Subjects 2,3,4,and 5.The MN frequencies 1 month after the accident of Subjects 3,4,and 5 were all significantly lower than those 16 h later(u=6.874,4.526,and 7.811,P<0.05).Conclusions Quick and accurate.CBMN assay reinforces and verifies the result of chromosome aberration analysis.The new index CBMN+NDI assay is of reference valne for estimating higher dose of irradiation.
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Objective Beagle dogs were subjected to hemorrhagic shock plus resuscitation and endotoxiemia (two-hit) to set up multiple organ dysfunction syndrome (MODS) model. In the study, this model can be used to monitor the responses of organ compensation and in compensation. Method Seven male Beagle dogs, weight ( 15 ± 2) kg, were provided by animal experiment centre of Xinjiang Medical University. MODS model was set up in 7 Beagle dogs. Hemorrhagic shock was produced according to the method of Wigger. After the resuscitation,Escherichia coli endotoxin was given via the femoral vein at a dose of 1.5 mg/kg. The criteria of MODS were defined as the presence of two or more of organ dysfunction. Clinical biochemical values were examined before making model and 0 h,3 h,6 h,9 h, 12 h after the establishment of model. The pathological change of the liver and the kidney were observed under the light microscopy. Results Significant differences of WBC,PaO2,LP,ALT, AST,Cr and BUN were observed after the establishment of model compared with those before the establishment of model ( P ＜ 0.05). Severe pathological lesions were observed in tissues of the liver and kidney. Conclusions Hemorrhagic shock and endotoxemia,a two-hit method, can be used to set up a delayed animal model for MODS to study the responses of organ dysfunction caused by ischemic and infectious diseases.
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Objective To establish a dose-effect curve of premature condensation chromosome ring (PCC-R)in lymphocytes of human peripheral blood after exposed to high doses of Y-rays. Methods Peripheral blood samples was drawn from three healthy individuals, and exposed to 60Co γ-rays with doses between 0 and 30 Gy. The frequencies of PCC-R in premature condensation chromosome (PCC) cells obtained by Okadaic acid (OA) induction were calculated, and a dose-effect curve was fitted. Results PCC index tapered with dose. Frequencies of PCC-R per cell increased until 20 Gy, and then saturation was observed. The results were fitted to a lineal model up to 20 Gy: y = - 0.020 + 0.052D ,where y was the frequencies of PCC-R per cell, D was the radiation dose (Gy). Conclusins The highest dose could be estimated is 20 Gy by the dose-effect curve established with PCC-R method. Its utility and validity will be verified in the future application of radiation accident.
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Objective To investigate the effects of continuous vennvenous haemodiafihration(CVVHDF)on major organ fimction and plasma cytokine levels in MODS dogs.Methods Fifteen Beagle dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then dogs were randomly divided into 2 groups:CVVHDF group(n=8)and MODS group without CVVHDF (n=7).CVVHDF was performed for 12 hours after endotoxin injection in CVVHDF group dogs.Serum ALT,AST,Scr,BUN and blood gas were routinely measured,and plasma TNF-α,IL-6 and IL-10 coneentrations were measured by ELISA at different time points. Results Plasma levels of IL-6 and IL-10 were significantly decreased in the CVVHDF group at 3 h,6 h,9 h and 12 h after endotoxin injection as compared with MODS group (P＜0.01).TNF-α levels were similar in both groups(P＞0.05).IL-6 and TNF-α were detected in the ultrafihrate.The sieving coefficients (SC) for IL-6 and TNF-α were 0.27±0.13 and 0.1±0.1 respectively.IL-10 could not be detected in the ultrafiltrate.In CVVHDF group,function of major organs was improved.The beneficial effect of CVVHDF on the hypotension of MODS dogs was particularly striking at 6 h,9 h,and 12 h alter endotoxin injection(P＜0.01).Mean PaO2 in CVVHDF groups at 3 h,6 h,9 h,and 12 h after endotoxin injection was significantly higher than that in MODS group(P＜0.01). Conclusion CVVHDF effectively removes IL-6 and IL-10from the cireulation,attennates endotoxin-induced hypotension and improves arterial oxygenation in MODS dogs.
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By use of color Doppler ultrasonography (ATLHDI 5000,made in USA),a prospective study was made in 362 aged (greater than or equal to 60 years) patients (252 males and 110 females) for a period of 3 years.There were 176 patients (48.2%,130 males and 46 females) had degenerative vavular disease (DVD).The incidence increased with the aging of the population.There were no evident differences between males and females.Degenerative aortic valvular deformation was most frequently found (in 171 cases),followed by mitral (in 24 cases).The complications were hypertension,diabetes and coronary heart disease.It suggests that the DVD in the elderly mainly occurs in aortic valves,then in mitral value.Its incidence increases with aging.Complications such as hypertension,diabetes and coronary heart disease are important risk factors of DVD.