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 investigate the incidence, risk factors, and outcomes of falls among the elderly community population in Beijing.Methods:A cross-sectional survey was conducted using stratified multistage random sampling to select urban and rural residents aged 65 years and older in Beijing. Mortality data was collected after the baseline survey for 5 years. The incidence of falls was weighted based on the composition ratios of age and gender from the 2010 Nation-wide Population Census of Beijing. A logistic regression model was used to analyze the impacts of demographic sociology of common chronic diseases on fall occurrence. The Cox proportional hazards regression model was used to analyze the fall and 5-year survival association.Results:A total of 2 968 participants completed the questionnaire, at cross-sectional survey, with an average age of (73.2±6.0) years, and 1 581 (53.8%) participants were female. Three hundred and sixty-one individuals experienced a fall within the past year. Among those who fell, 64 (17.7%) fell twice, and 95 (26.6%) fell three or more times. Of them, 14.4% (52) had post-fall fractures, with the wrist, knee, and hip being the most common fracture sites, accounting for 25.0%, 17.3%, and 15.4%, respectively. The weighted fall incidence was 12.4% (95% CI: 11.2%-13.5%). Aging, being female, and living in rural areas were more likely to fall. Logistic regression analysis showed that after adjusting for age, gender, and urban-rural status, the risk of falls for those living alone ( OR=1.48, 95% CI: 1.08-2.04) or living with children/grandchildren ( OR=1.51, 95% CI: 1.15-1.97) were significantly higher than those living with their spouse. In addition, the risk of falls was elevated significantly among the elderly with hypertension, diabetes, stroke, dementia, depression status, urinary incontinence, arthritis, insomnia, vision, and hearing loss, dependence on activities of daily living (ADL), general and poor self-rated health (SRH). The Cox proportional hazard regression model revealed that the 5-year risk of death increased by 65% ( HR=1.65, 95% CI: 1.29-2.11) for those who experienced a fall, which increased with fall frequency. This elevated risk persisted after adjusting for chronic conditions, ADL, and SRH. Conclusions:Ageing, female, living in rural regions, having common chronic diseases, dependence on ADL, general and poor SRH, living alone or living with children/grandchildren were associated with the elevated fall risk. The occurrence of fall was seasonal. The most common short-term adverse consequence after a fall was fractures, while the long-term effect was an increased risk of death.

Objective:To investigate the utilization of inpatient service and influencing factors among pneumoconiosis patients in Chongqing within one year, and to provide a reference basis for the formulation of relevant policies by health management departments.Methods:From October 2020 to October 2023, a multi-stage cluster random sampling method was adopted to select 2002 patients with confirmed pneumoconiosis as the research subjects. A questionnaire survey was conducted on their basic information, inpatient service utilization within one year, treatment for pneumoconiosis-related symptoms, and choice of medical service institutions. Chi-square test and logistic regression were used for statistical analysis.Results:All 2002 pneumoconiosis patients were male, with 40.16% (804/2002) aged 46-55 years old, and 83.32% (1668/2002) currently residing in rural areas. The monthly income of the patients was 833 (167, 2000) yuan, and 22.03% (441/2002) had no income. 30.97% (620/2002) of the patients spent more than 5001 yuan per year on treatment for pneumoconiosis, and 14.64% (293/2002) had debts of more than 5001 yuan. 42.06% (842/2002) had no work-related injury insurance. 21.68% (434/2002) of the patients self-assessed their health status as very poor or poor. The one-year inpatient rate of the patients was 51.25% (1026/2002), and the total inpatient time within one year was 18 (10, 51) days. The inpatient expenses were 6000 (1000, 16625) yuan. Through univariate analysis, the one-year inpatient rates of pneumoconiosis patients were statistically significantly different among different age groups, current employment status, annual household income levels, types of pneumoconiosis, stages of pneumoconiosis, presence or absence of work-related injury insurance, whether receiving minimum living allowances and social assistance related to pneumoconiosis, and different segments of self-assessed health status ( P<0.05). Patients with stage Ⅲ pneumoconiosis, those who received social assistance and minimum living allowances related to pneumoconiosis had higher one-year inpatient rates ( P<0.05), with OR values of 3.893, 1.859, and 2.589, respectively. Conclusion:The utilization of inpatient service by pneumoconiosis patients is influenced by demographic characteristics, social support, and disease factors. It is necessary to enhance the occupational disease diagnosis and treatment capabilities of primary health institutions, build a multi-level social support network, and ensure that patients can conveniently access medical services.

Objective:To investigate the incidence, risk factors, and outcomes of falls among the elderly community population in Beijing.Methods:A cross-sectional survey was conducted using stratified multistage random sampling to select urban and rural residents aged 65 years and older in Beijing. Mortality data was collected after the baseline survey for 5 years. The incidence of falls was weighted based on the composition ratios of age and gender from the 2010 Nation-wide Population Census of Beijing. A logistic regression model was used to analyze the impacts of demographic sociology of common chronic diseases on fall occurrence. The Cox proportional hazards regression model was used to analyze the fall and 5-year survival association.Results:A total of 2 968 participants completed the questionnaire, at cross-sectional survey, with an average age of (73.2±6.0) years, and 1 581 (53.8%) participants were female. Three hundred and sixty-one individuals experienced a fall within the past year. Among those who fell, 64 (17.7%) fell twice, and 95 (26.6%) fell three or more times. Of them, 14.4% (52) had post-fall fractures, with the wrist, knee, and hip being the most common fracture sites, accounting for 25.0%, 17.3%, and 15.4%, respectively. The weighted fall incidence was 12.4% (95% CI: 11.2%-13.5%). Aging, being female, and living in rural areas were more likely to fall. Logistic regression analysis showed that after adjusting for age, gender, and urban-rural status, the risk of falls for those living alone ( OR=1.48, 95% CI: 1.08-2.04) or living with children/grandchildren ( OR=1.51, 95% CI: 1.15-1.97) were significantly higher than those living with their spouse. In addition, the risk of falls was elevated significantly among the elderly with hypertension, diabetes, stroke, dementia, depression status, urinary incontinence, arthritis, insomnia, vision, and hearing loss, dependence on activities of daily living (ADL), general and poor self-rated health (SRH). The Cox proportional hazard regression model revealed that the 5-year risk of death increased by 65% ( HR=1.65, 95% CI: 1.29-2.11) for those who experienced a fall, which increased with fall frequency. This elevated risk persisted after adjusting for chronic conditions, ADL, and SRH. Conclusions:Ageing, female, living in rural regions, having common chronic diseases, dependence on ADL, general and poor SRH, living alone or living with children/grandchildren were associated with the elevated fall risk. The occurrence of fall was seasonal. The most common short-term adverse consequence after a fall was fractures, while the long-term effect was an increased risk of death.

Objective:To investigate the utilization of inpatient service and influencing factors among pneumoconiosis patients in Chongqing within one year, and to provide a reference basis for the formulation of relevant policies by health management departments.Methods:From October 2020 to October 2023, a multi-stage cluster random sampling method was adopted to select 2002 patients with confirmed pneumoconiosis as the research subjects. A questionnaire survey was conducted on their basic information, inpatient service utilization within one year, treatment for pneumoconiosis-related symptoms, and choice of medical service institutions. Chi-square test and logistic regression were used for statistical analysis.Results:All 2002 pneumoconiosis patients were male, with 40.16% (804/2002) aged 46-55 years old, and 83.32% (1668/2002) currently residing in rural areas. The monthly income of the patients was 833 (167, 2000) yuan, and 22.03% (441/2002) had no income. 30.97% (620/2002) of the patients spent more than 5001 yuan per year on treatment for pneumoconiosis, and 14.64% (293/2002) had debts of more than 5001 yuan. 42.06% (842/2002) had no work-related injury insurance. 21.68% (434/2002) of the patients self-assessed their health status as very poor or poor. The one-year inpatient rate of the patients was 51.25% (1026/2002), and the total inpatient time within one year was 18 (10, 51) days. The inpatient expenses were 6000 (1000, 16625) yuan. Through univariate analysis, the one-year inpatient rates of pneumoconiosis patients were statistically significantly different among different age groups, current employment status, annual household income levels, types of pneumoconiosis, stages of pneumoconiosis, presence or absence of work-related injury insurance, whether receiving minimum living allowances and social assistance related to pneumoconiosis, and different segments of self-assessed health status ( P<0.05). Patients with stage Ⅲ pneumoconiosis, those who received social assistance and minimum living allowances related to pneumoconiosis had higher one-year inpatient rates ( P<0.05), with OR values of 3.893, 1.859, and 2.589, respectively. Conclusion:The utilization of inpatient service by pneumoconiosis patients is influenced by demographic characteristics, social support, and disease factors. It is necessary to enhance the occupational disease diagnosis and treatment capabilities of primary health institutions, build a multi-level social support network, and ensure that patients can conveniently access medical services.

Objective To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva. Methods We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma. Results The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression?free survival was 90.0 months. The 5?year progression?free survival rate of the total patients was 55.5%, while the 10?year progression?free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode ( all P＜0.001 ). Multivariate analysis showed that number of metastatic lymph nodes ( P＜0.05 ) was an independent prognostic factor for progression?free survival. Conclusion The study illustrates that number of metastatic lymph nodes represents important independent factor for progression?free survival of patients with vulvar squamous cell carcinoma.

Objective To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva. Methods We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma. Results The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression?free survival was 90.0 months. The 5?year progression?free survival rate of the total patients was 55.5%, while the 10?year progression?free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode ( all P＜0.001 ). Multivariate analysis showed that number of metastatic lymph nodes ( P＜0.05 ) was an independent prognostic factor for progression?free survival. Conclusion The study illustrates that number of metastatic lymph nodes represents important independent factor for progression?free survival of patients with vulvar squamous cell carcinoma.

Objective: To evaluate the significance of different clinicopathologic features on prognosis of patients with squamous cell carcinoma of vulva. Methods: We retrospectively analyzed the prognostic relevance of different clinicopathological variables of 201 patients with squamous cell carcinoma of vulva treated in Cancer Hospital, Chinese Academy of Medical Sciences. The data including age, initial symptoms, stage, location, tumor size, histological grade, number and size of metastatic lymph nodes, treatment mode, and presence of leukoplakia vulva was used to evaluate the prognosis of vulvar squamous cell carcinoma. Results: The median age of onset was 62.0 years old, with 74 patients in stage Ⅰ, 27 in stage Ⅱ, 55 in stage Ⅲ and 9 in stage Ⅳ. The median progression-free survival was 90.0 months. The 5-year progression-free survival rate of the total patients was 55.5%, while the 10-year progression-free survival rate was 48.5%. Univariate analysis showed statistically significant prognostic parameters included clinical stage, number of metastatic lymph nodes, tumor size and treatment mode (all P<0.001). Multivariate analysis showed that number of metastatic lymph nodes (P<0.05) was an independent prognostic factor for progression-free survival. Conclusion The study illustrates that number of metastatic lymph nodes represents important independent factor for progression-free survival of patients with vulvar squamous cell carcinoma.

Objective To investigate the prognosis of patients with solitary large hepatocellular carcinoma (SLHCC) and with small hepatocellular carcinoma (SHCC),and analyze the risk factors affecting the prognosis of patients with SLHCC.Methods The retrospective case-control study was conducted.The clinicopathological data of 856 patients with hepatitis B virus (HBV)-related HCC who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2008 to December 2008 were collected.Of 856 patients,693 HCC patients with tumor diameter ≤5 cm were allocated into the SHCC group and 163 HCC patients with tumor diameter ＞ 5 cm and with solitary,expansive growth and complete capsule tumors were allocated into the SLHCC group.Patients underwent preoperative antiviral therapy,laboratory and imaging examinations,and then surgical planning was determined based on the preoperative results.Observation indicators:(1) comparisons of clinicopathological features between the 2 groups:sex,age,Child-Pugh grade,HBeAg,serum level of HBV-DNA,platelet (PLT),albumin (Alb),total bilirubin (TBil),alpha-fetoprotein (AFP),tumor diameter,microvascular invasion,Edmondson-Steiner grade and liver cirrhosis;(2) treatment situations between the 2 groups:surgical procedures,operation time,volume of intraoperative blood loss,number of patients with blood transfusion and time of hepatic inflow occlusion;(3) survival analysis between the 2 groups;(4) prognostic analysis of patients with SLHCC.Follow-up using telephone interview and outpatient examination was performed once every 3 months within 2 years postoperatively and once every 6 months after 2 years postoperatively up to June 23,2014.Follow-up included tumor marker,liver function,serum level of HBV-DNA and abdominal B-ultrasound examination.The patients received reexamination of computed tomography (CT) or magnetic resonance imaging (MRI) once every 6 months or when there was suspicion of tumor recurrence or metastasis.Tumor recurrence or metastasis was confirmed through typical HCC imaging findings of CT and MRI,and PET/CT examination was conducted if necessary.Tumor-free survival time was from operation time to time of tumor recurrence,and overall survival time was from operation time to death or the last follow-up.Measurement data with normal distribution were represented as-x±s,and continuous variables were analyzed by the t test or Mann-Whitney U test.Measurement data with skewed distribution were described as M (range).Categorical variables were represented as count (percentage) and analyzed by the chi-square test or calibration chi-square test.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method and Log-rank test.COX regression model was used for prognostic analysis.Results (1) Comparisons of clinicopathological features between the 2 groups:number of patients with PLT＜ 100× 109/L,with positive microvascular invasion and with liver cirrhosis and tumor diameter were 197,133,447,(3.1±1.1)cm in the SHCC group and 28,53,79,(8.9±3.3) cm in the SLHCC group,respectively,with significant differences between the 2 groups (x2=28.618,t =37.286,x2 =213.773,214.325,P ＜ 0.05).(2) Treatment situations between the 2 groups:all the 856 patients underwent hepatectomy,including 326 with hepatic segments of resection ≥ 3 and 530 with hepatic segments of resection ＜ 3.Operation time,volume of intraoperative blood loss,number of patients with intraoperative blood transfusion and with time of hepatic inflow occlusion ＞ 20 minutes were 90 minutes (range,60-200 minutes),200 mL (range,20-5 200 mL),47,125 in the SHCC group and 110 minutes (range,60-230 min),300 mL (range,50-3 200 mL),31,58 in the SLHCC group,respectively.(3) Survival analysis between the 2 groups:all the 856 patients were followed up for 32.5 months (range,1.O-72.3 months).The median survival time,median tumor-free survival time,1-,3-,5-year overall survival rates and 1-,3-,5-year tumor-free survival rates were 56.2 months (range,1.6-75.8 months),39.5 months(range,1.0-75.0 months),90％,71％,58％,70％,48％,38％ in the SHCC and 50.3 months (range,1.1-76.0 months),30.7 months (range,1.0-72.0 months),87％,59％,47％,65％,46％,33％ in the SLHCC group,respectively,with no significant difference in tumor-free survival between the 2 groups (x2=0.514,P＞0.05) and with a significant difference in overall survival between the 2 groups (x2=10.067,P＜0.05).Stratified analysis:there were 117 SLHCC patients with 5 cm ＜ tumor diameter ＜ 10 cm and 46 SLHCC patients with tumor diameter ＞ 10 cm.The 1-,3-,5-year overall survival rates and 1-,3-,5-year tumor-free survival rates were 91％,65％,53％,70％,48％,35％ in 117 SLHCC patients with 5 cm ＜ tumor diameter ＜ 10 cm,respectively,with no significant difference compared with SHCC group (x2=1.832,0.042,P＞0.05).The 1-,3-,5-year overall survival rates and 1-,3-,5-year tumor-free survival rates were 78％,46％,31％,49％,39％,30％ in 46 SLHCC patients with tumor diameter ＞ 10 cm,respectively,with significant differences compared with SHCC group (x2=21.136,4.097,P＜0.05).(4) Prognostic analysis of patients with SLHCC:results of univariate analysis showed that serum level of HBV-DNA,tumor diameter and microvascular invasion were risk factors affecting postoperative 5-year tumor-free survival rate of SLHCC patients (x2 =5.193,3.377,5.509,P＜0.05);sex,serum level of HBV-DNA,tumor diameter and microvascular invasion were risk factors affecting postoperative 5-year overall survival rate of SLHCC patients (x2=4.546,18.053,7.780,10.569,P＜0.05).Results of multivariate analysis showed that serum level of HBV-DNA ≥ 104 U/mL,tumor diameter ＞ 10 cm and positive microvascular invasion were independent risk factors affecting postoperative 5-year tumor-free survival rate of SLHCC patients [HR =2.77,1.85,1.86,95％ confidence interval (CI):1.74-4.40,1.16-2.94,1.17-2.96,P＜ 0.05] and affecting postoperative 5-year overall survival rate of SLHCC patients (HR=2.73,1.98,1.69,95％CI:1.72-4.33,1.23-3.17,1.04-2.72,P＜0.05).Conclusions There are similar prognosis between SLHCC patients with 5 cm ＜ tumor diameter ＜ 10 cm and SHCC patients,however,prognosis of SLHCC patients with tumor diameter ＞ 10 cm is worse than that of SHCC patients.Serum level of HBV-DNA ≥ 104 U/mL,tumor diameter ＞ 10 cm and positive microvascular invasion are independent risk factors affecting prognosis of SLHCC patients.

Objective To investigate the nuclear factor-erythroid 2-related factor (Nrf-2),and heme oxidase 1 (HO-1) expression in acute lung injury induced by paraquat poisoning in rats and explore the mechanism of lipoic acid acting on protection of lung from paraquat poisoning.Methods Seventy-two adult healthy male Sprague Dawley (SD) rats were randomly divided into three groups with different treatments designated as:control group (control group,n =12),paraquat group (PQ group,n =30) and paraquat + lipoic acid group (LA group,n =30).PQ group and LA group were randomly divided into five subgroups (n =6 in each) according to 6 h,12 h,24 h,48 h and 72 h after modeling and treatment.The rats in PQ group and PQ + LA group were treated with intra-peritoneal injection (ip) of PQ (25 mg/kg),while the rats in control group were treated with the equal volume of saline instead.Half an hours after intra-peritoneal injection of PQ,lipoic acid (100 mg/kg) was injected into caudal vein of rats once a day until they were sacrificed.The body weight was measured everyday.The rats of each group were sacrificed at the given intervals,and lung tissues were harvested to measure lung coefficient of rats.The same part of left lung of rats in each group was taken for HE staining and immunohistochemistry in order to detect the expressions of Nrf2 and HO-1.The right lung of rats in each group was taken for the detection of GSH-Px and SOD activity.All data were analyzed by using the One-way analysis of variance (ANOVA) and SNK-q test.Results The body weight reduction in LA group (191.02 ± 0.82) g,(183.37 ± 7.74) g was significantly less than that in PQ group (183.85 ± 2.07) g,(173.13 ± 4.34) g at 48 h and 72 h after PQ poisoning,respectively (P ＜ 0.01,P ＜ 0.05).The lung coefficient in LA group (6.83 ± 0.48) mg/g,(7.61 ±0.28) mg/g,(8.29 ±0.36) mg/g was less compared with PQ group (7.39 ±0.53) mg/g,(8.48±0.23) mg/g,(9.06±0.10) mg/g at 24 h,48 h,and 72 h,respectively (P＜0.01,P＜ 0.05).The immunohistochemical expressions of Nrf-2 in LA group (3.99 ±0.50),(3.51 ±0.12) were higher than those in PQ group (1.33 ±0.22),(1.62 ±0.41) at 48 h and 72 h.The immunohistochemical expression of HO-1 in LA group (1.76 ±0.17) was higher than that in PQ group (1.31 ±0.15) at 72 h.The levels of GSH-Px activity in LA group were significantly higher in comparison with PQ group at 24h,48h,and 72h (P ＜0.01,P ＜0.05).The levels of SOD activity in the LA group were significantly higher in comparison with PQ group at 6 h,12 h,24 h,48 h,and 72 h after PQ administration (P ＜ 0.01).Conclusions Nrf2-ARE (antioxidant response element) signaling pathway is involved in the pathogenesis of acute lung injury induced by paraquat poisoning,and lipoic acid may protect acute lung injury in rats induced by paraquat poisoning through Nrf2-ARE signaling pathway.