BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective:To explore the effects of neonatal stimulator of interferon genes (STING) innate immune signaling pathway of HBsAg-positive mothers on non/hypo-response to hepatitis B vaccine (HepB) in their infants.Methods:From November 2019 to June 2022, HBsAg-positive mothers and their infants in the Third People's Hospital of Taiyuan were recruited as the study subjects. The epidemiological and clinical data were collected by questionnaire survey and medical records review. The key molecular proteins of STING innate immune signaling pathway (STING, pIRF3) and immune cells associated with vaccine response (DC, T and B and plasma cells) in neonatal cord blood were detected by flow cytometry. Follow up was conducted for infants for 1-2 months after the full vaccination of HepB. Serum hepatitis B surface antibody (anti-HBs) was detected by chemiluminescence microparticle immunoassay. Unconditional logistic regression model, nomogram and Bayesian network model were used to evaluate the effect of STING innate immune signaling pathway on non/hypo-response to HepB and related factors in infants, and the relationship between various factors.Results:A total of 195 pairs of HBsAg-positive mothers and infants were recruited, the rate of non/hypo-response to HepB in the infants was 12.31% (24/195). High maternal HBV DNA load, low expression of neonatal STING, low expression of pIRF3 and low percentage of plasma cells were risk factors for non/hypo-response to HepB in the infants ( OR=4.70, 3.46, 3.18 and 2.20, all P<0.05). The nomogram constructed by these factors had good predictive efficacy (area under curve=0.81, 95% CI: 0.63-0.83). The results of Bayesian network model showed that the infants with a high maternal HBV DNA load had a higher conditional probability of low STING expression (62.50%) and a higher conditional probability of low pIRF3 expression (58.54%). The conditional probabilities of low expression of DC, T, B and plasma cells were 53.16%, 60.20%, 68.42% and 57.14%, respectively. Conclusion:Maternal HBV DNA might inhibit STING innate immune signaling pathways in infants and immune cells associated with HepB response, resulting in non/hypo-response to HepB in infants of HBsAg-positive mothers.

Objective:To explore the prevalence of hepatitis C virus (HCV) infection, influence factors and interaction on HCV infection in patients receiving methadone maintenance treatment (MMT) in Taiyuan.Methods:Between April-June 2019, three MMT clinics in Taiyuan were selected to conduct a face-to-face questionnaire survey among MMT patients to collect the information about their socio-demographic characteristics, drug use, MMT, sexual behavior and health status. Software EpiData 3.1 was used for real-time double entry to establish the database. Software SAS 9.4 was used to analyze the data, and χ 2 test was used for univariate analysis and logistic regression model was used for multivariate and interaction analyses. Results:A total of 903 subjects were surveyed among MMT patients, the male to female ratio of was 7.21∶1(743∶103), and the rate of HCV infection was 12.53% (106/846). After adjusting for the confounding factors, being women ( OR=1.936, 95% CI: 1.023-3.662), having sex with drug users ( OR=2.073, 95% CI: 1.110-3.871) and injection drug use ( OR=7.737, 95% CI: 4.614-12.973) might be the risk factors for HCV infection in patients receiving MMT. The results showed that there were multiplicative interactions among women, having sex with drug user and injection drug use on HCV infection. Conclusions:Being women, having sex with drug user and injection drug use were associated with higher risk for HCV infection in patients receiving MMT in Taiyuan. There were multiplication interactions between being women and having sex with drug user, being female and injection drug use, and having sex with drug use and injection drug use on HCV infection.

Objective:To compare the anti-HBs level in maintained hemodialysis patients one year after receiving 20 μg and 60 μg hepatitis B vaccination at 0, 1 and 6 months, and explore the influence factors for the immunity persistence and their interactions.Methods:Based on a randomized controlled trial of 20 μg and 60 μg hepatitis B vaccine immunization in maintained hemodialysis patients at 0, 1, and 6 months, follow up was conducted for the patients for one year after the completion of the vaccination for the quantitative detection of anti-HBs, and χ 2 test, t test, unconditional logistic regression and interaction analyses were used for statistical analysis. Results:One year after the vaccination, 125 and 124 patients in the 20 μg and 60 μg groups were tested for anti-HBs, respectively. The positive rate of anti-HBs in the 60 μg group (77.42%, 96/124) was significantly higher than that in the 20 μg group (65.60%, 82/125) ( P<0.05). After adjusting for the confounding factors, the positive probability of anti-HBs in the 60 μg group was 1.925 times higher than that in the 20 μg group (95% CI: 1.068-3.468). Patients with hemodialysis duration ≥5 years ( OR=0.523, 95% CI: 0.293-0.935) and diabetes mellitus ( OR=0.376, 95% CI: 0.173-0.818) had lower positive probability of anti-HBs. Moreover, there were additive and multiplicative interactions between hemodialysis duration ≥5 years and diabetes mellitus. Conclusions:The immunity persistence after one year in 60 μg hepatitis B vaccination group was longer than that in 20 μg hepatitis B vaccination group in maintained hemodialysis patients, vaccine dose, hemodialysis duration and diabetes mellitus were the influencing factors for the immunity persistence, there were additive and multiplicative interactions between hemodialysis duration ≥5 years and diabetes mellitus.

Objective:To investigate the effects of TNF-α knockout on liver and spleen neutrophil responses to Vibrio vulnificus bloodstream infection in a mouse model. Methods:(1) TNF-α-knockout (TNF-α -/-) and wild-type (WT) C57BL/6J mice aged 6-8 weeks were randomly divided into four groups with six in each group: uninfected WT group, infected WT group, uninfected TNF-α -/- group and infected TNF-α -/- group. The mouse model of bloodstream infection was constructed by intraperitoneal injection of Vibrio vulnificus CGMCC1.1758 (2×10 8 CFU/200 μl), while the mice in the uninfected groups were injected intraperitoneally with equal amount of PBS. (2) Liver immune cells and splenocytes were isolated 4 h after infection and subjected to analyze the percentages and numbers of neutrophils, and the changes in cell viability, cellular reactive oxygen species (ROS) level and phagocytosis by flow cytometry. In addition, effects of Vibrio vulnificus bloodstream infection on mTOR signaling pathway in murine neutrophils were evaluated in vivo. Results:(1)Compared with the uninfected WT group, the percentages and numbers of neutrophils in liver and spleen tissues of the infected WT group increased significantly. The percentage and number of liver neutrophils were significantly higher in the infected TNF-α -/- group than in the infected WT group, but no significant difference in spleen neutrophils was detected between the two groups. (2) Compared with the infected WT group, the phagocytosis of liver neutrophils rather than that of spleen neutrophils was enhanced in the infected TNF-α -/- group. (3) The survival rates of neutrophils in both liver and spleen were decreased, while the cellular ROS level was significantly increased in the infected WT group compared with those of the uninfected WT group. Compared with the infected WT group, the infected TNF-α -/- group had increased survival rates of both liver and spleen neutrophils, but decreased level of ROS. (4) The levels of p-AKT (S473) in liver and spleen neutrophils of the infected WT group were lower than those of the uninfected WT group. Compared with the infected WT group, the infected TNF-α -/- group had lower level of p-AKT (S473) in liver neutrophils, but higher p-AKT (S473) level in spleen neutrophils. There were no significant differences in p-4E-BP1(T37/46) levels between the uninfected WT group and the infected WT group. The p-4E-BP1 (T37/46) level in liver neutrophils was lower in the infected TNF-α -/- group than in the infected WT group, but no significant difference in p-4E-BP1 (T37/46) levels in spleen neutrophils was observed between the two groups. Conclusions:TNF-α had different effects on the neutrophils in spleen and liver tissues of mice with Vibrio vulnificus bloodstream infection. It played a critical role in regulating the recruitment, phagocytic function and mTOR signaling of liver neutrophils after Vibrio vulnificus infection in vivo.

Objective:To understand the characteristics and explore the influencing factors of HBsAg positivity in methadone maintenance treatment (MMT) clinic patients.Methods:A face to face interview and medical record review were conducted in 1 040 patients at three MMT clinics in Guangxi from September to November in 2014. The questionnaire information included general demographic characteristics, drug use history, MMT status, sexual behaviors, and health status, etc. Blood samples were collected from the patients at the same time for the detections of the level of HBsAg, anti-HBs and anti-HCV. By using χ2 test, unconditional logistic regression model and Bayesian network model the influencing factors for HBsAg positivity in MMT clinic patients and the complex network relationship among these factors were explored. Results:A total of 1 031 MMT clinic patients were surveyed, the HBsAg positive rate was 11.35 % (117/1 031). The anti-HCV positive rate was 71.77 % (740/1 031), among the anti-HCV positive patients, the HBsAg positive rate was 10.27 % (76/740). After adjusting for the confounding factors, anti-HBs positive persons might not be HBsAg positive ( OR=0.05, 95 %CI: 0.03-0.09), and anti-HCV positive persons might not be HBsAg positive too ( OR=0.30, 95 %CI: 0.17-0.52) compared with anti-HBs negative and anti-HCV negative persons, respectively. The persons with family history of hepatitis B virus infection were more likely to be HBsAg positive compared those with no such family history ( OR=5.30, 95 %CI: 2.68-10.52). Bayesian network model analysis results showed that family history of hepatitis B virus infection and anti-HBs were directly related with HBsAg positivity. Anti-HCV, intravenous drug use in the past three months and other drug using during treatment were indirectly related with HBsAg positivity. Conclusions:Anti-HBs, family history of hepatitis B virus infection, anti-HCV, intravenous drug use in past three months and other drug use during treatment were related with the HBsAg positivity in MMT clinic patients. So, it is necessary to enhance health education, improve health awareness and decrease high risk behaviors to reduce the rate of HBV infection.

Multiple sclerosis (MS) is a disease characterized as inflammatory demyelinating of the central nervous system,which is the main cause of non-traumatic neurological disability in young and middle-age adults.The main manifestations of MS are memory and information processing speed,executive function and other cognitive impairments.MS associated with memory impairment (MSMI) is often overlooked because of the occult onset,which seriously affecting patients' life quality.In recent years,with the rapid development of neuro-functional imaging,MRI has become an important method to observe and diagnose MS,providing imaging evidence for diagnosis of MSMI.The clinical and MRI research progresses of MEMI were reviewed in this article.

Objective To estimate the incidence of drop out of treatment in patients with access to methadone maintenance treatment and explore the correlation and interaction between insufficient methadone dosage and morphine positive urine on the drop out in Guangxi Zhuang Autonomous Region.Methods Face to face interview was conducted in 1 031 patients at 3 methadone maintenance treatment clinics in Guangxi.Results The study included 1 031 participants,40.6％ of them (419/1 031) had stopped treatment.The drop out rates in urine morphine positive group and methadone dosage ＜ 100 mg/d group were 57.6％ (99/172) and 37.4％ (347/929) respectively,higher than those in urine morphine negative group and methadone dosage ≥ 100 mg/d group (42.3％,363/ 859,and 26.5％,27/102).Orderly logistic regression analysis results showed that after adjusted factors,such as gender,age,marital status,ethnic group,patients who received a dosage less than 1 00 mg/day (OR=3.05,95％CI:1.84-5.06) and had morphine positive urine (OR=2.25,95％CI:1.59-3.19) were more likely to drop out of the treatment.Interaction analysis showed that dosage less than 100 mg/d and morphine positive urine during treatment had additive interaction (RERI=256.46,AP=0.87,S=8.05) and multiplication interaction (OR=2.45,95％CI:1.71-3.49).Conclusion Insufficient dosage and morphine positive urine were significantly correlated with drop out of treatment in patients with access to methadone maintenance treatment.

Objective To reveal the prevalence and the related factors of hepatitis B (HepB) virus infection among HIV/AIDS patients.Methods We conducted a cross-sectional study in two HIV clinics,affiliated to local Centers of Disease Control and Prevention in Guangxi Zhuang Autonomous Regional.A face-to-face interview,with questionnaire was conducted to collect information on socio-demographic characteristics,drug use,and sexual behavior.Blood samples were used to test HBsAg.x2 test or Fisher's exact test and unconditional logistic regression models were used to identify the influencing factors.Results The prevalence of HBV and HIV co-infection was 13.85％ (113/816).Results from multivariate logistic regression analyses showed that age (25-45),family history of HBV and history of HepB vaccination were independent influencing factors for HBV and HIV coinfection,with OR (95％ CI) as 1.738 (1.031-2.931),2.898 (1.678-5.005) and 1.744 (1.052-2.892),respectively.Conclusion The prevalence of HBV among HIV/AIDS patients was significantly higher than that in general population.HIV/AIDS patients aged between 25 and 45 and with family history of HBV were more likely to be infected with HBV,while HepB vaccination was associated with the reduction of HIV/HBV coinfection.Specific comprehensive prevention and treatment programs on HIV/AIDS patients need to be set up.

Long terms of chronic pain may induce emotional disorder such as depression,anxiety and aversion.It is worthy of studying the mechanism and therapy on pain emotional disorder.The animal model is important in basic researches,and the quantitative evaluation methods on the psychiatric factors are gradually applied in the pain research.The methods of evaluating the psychiatric disorder of pain are discussed in this paper,which will provide theory basis in the relevant fields.