BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

AIM:This study aims to investigate the protective effect of α-lipoic acid(α-LA)against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms.METHODS:An alcohol-induced injury model of H9c2 cells was established,and the cells were divided into 4 groups:control group,alcohol group,α-LA group,and alcohol+α-LA group.Additionally,H9c2 cells overexpressing aldehyde dehydrogenase 2(ALDH2)were cre-ated and further divided into 6 groups:normal control group,normal cells treated with alcohol group,normal cells treated with alcohol+α-LA group,ALDH2 overexpression group,ALDH2-overexpressing cardiomyocytes treated with alcohol group,and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group.Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine(EdU)staining.Reactive oxygen species(ROS)levels in each group were measured using di-hydroethidium(DHE)staining,while the expression levels of ALDH2,silent information regulator 1(SIRT1),heme oxy-genase 1(HO1)and P53 proteins were detected by Western blot analysis.RESULTS:(1)Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress,evidenced by elevated ROS levels and decreased expression of related proteins(ALDH2,SIRT1 and HO1).However,α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol.(2)Alcohol may induce cellular se-nescence,as demonstrated by the up-regulation of P53 expression,which were reversed by α-LA.(3)The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol,suppressed the ROS pro-duction,prevented the down-regulation of oxidative stress-related proteins(ALDH2,SIRT1 and HO1),and reversed the enhanced expression of the senescence marker P53.CONCLUSION:Treatment with α-LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2,thereby protecting cardiomyocytes from alcohol-induced damage.

Objective:To evaluate the efficacy and safety of modified endoscopic submucosal dissection (ESD) utilizing a mushroom extraction method for gastric ectopic pancreas.Methods:From June 1, 2009 to June 30, 2023, data of 190 patients (191 lesions) with pathologically confirmed heterotopic pancreas who underwent resection using modified ESD with mushroom extraction method in Shandong Second Provincial General Hospital ( n=99) and the 960th Hospital of the PLA Joint Logistics Support Force ( n=91) were retrospectively analyzed. The clinical characteristics and endoscopic and endoscopic ultrasonography (EUS) features were summarized and the treatment effects of the modified ESD was evaluated. The complications and follow-up recurrence were analyzed. Results:Preoperative EUS showed that most lesions originated from the submucosa and often involved multiple layers, invading the muscularis propria in 12 cases. A total of 191 gastric lesions included 174 in the gastric antrum, 2 pyloric canal, 6 gastric body, 7 gastric angle and 2 gastric fundus. The long diameter of the lesions ranged from 0.5-4.0 cm. All patients underwent modified ESD with the mushroom extraction method, and the complete removal rate of specimens was 99.5% (190/191). The operation time was 0.5-2.5 h. There were 10 cases of intraoperative perforation; 1 case of postoperative delayed perforation, 1 case of delayed hemorrhage, and 3 cases of short-term fever. Patients were followed up for 3-5 years after the operation, and no recurrence or metastasis was found.Conclusion:The modified ESD technique incorporating mushroom extraction proves to be a safe and effective approach for the complete removal of gastric ectopic pancreas, minimizing the risk of recurrence and residual pancreatic tissue.

Objective:To evaluate the efficacy and safety of modified endoscopic submucosal dissection (ESD) utilizing a mushroom extraction method for gastric ectopic pancreas.Methods:From June 1, 2009 to June 30, 2023, data of 190 patients (191 lesions) with pathologically confirmed heterotopic pancreas who underwent resection using modified ESD with mushroom extraction method in Shandong Second Provincial General Hospital ( n=99) and the 960th Hospital of the PLA Joint Logistics Support Force ( n=91) were retrospectively analyzed. The clinical characteristics and endoscopic and endoscopic ultrasonography (EUS) features were summarized and the treatment effects of the modified ESD was evaluated. The complications and follow-up recurrence were analyzed. Results:Preoperative EUS showed that most lesions originated from the submucosa and often involved multiple layers, invading the muscularis propria in 12 cases. A total of 191 gastric lesions included 174 in the gastric antrum, 2 pyloric canal, 6 gastric body, 7 gastric angle and 2 gastric fundus. The long diameter of the lesions ranged from 0.5-4.0 cm. All patients underwent modified ESD with the mushroom extraction method, and the complete removal rate of specimens was 99.5% (190/191). The operation time was 0.5-2.5 h. There were 10 cases of intraoperative perforation; 1 case of postoperative delayed perforation, 1 case of delayed hemorrhage, and 3 cases of short-term fever. Patients were followed up for 3-5 years after the operation, and no recurrence or metastasis was found.Conclusion:The modified ESD technique incorporating mushroom extraction proves to be a safe and effective approach for the complete removal of gastric ectopic pancreas, minimizing the risk of recurrence and residual pancreatic tissue.

AIM:This study aims to investigate the protective effect of α-lipoic acid(α-LA)against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms.METHODS:An alcohol-induced injury model of H9c2 cells was established,and the cells were divided into 4 groups:control group,alcohol group,α-LA group,and alcohol+α-LA group.Additionally,H9c2 cells overexpressing aldehyde dehydrogenase 2(ALDH2)were cre-ated and further divided into 6 groups:normal control group,normal cells treated with alcohol group,normal cells treated with alcohol+α-LA group,ALDH2 overexpression group,ALDH2-overexpressing cardiomyocytes treated with alcohol group,and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group.Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine(EdU)staining.Reactive oxygen species(ROS)levels in each group were measured using di-hydroethidium(DHE)staining,while the expression levels of ALDH2,silent information regulator 1(SIRT1),heme oxy-genase 1(HO1)and P53 proteins were detected by Western blot analysis.RESULTS:(1)Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress,evidenced by elevated ROS levels and decreased expression of related proteins(ALDH2,SIRT1 and HO1).However,α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol.(2)Alcohol may induce cellular se-nescence,as demonstrated by the up-regulation of P53 expression,which were reversed by α-LA.(3)The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol,suppressed the ROS pro-duction,prevented the down-regulation of oxidative stress-related proteins(ALDH2,SIRT1 and HO1),and reversed the enhanced expression of the senescence marker P53.CONCLUSION:Treatment with α-LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2,thereby protecting cardiomyocytes from alcohol-induced damage.

AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.

An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats ; Animals ; Kainic Acid/toxicity* ; Brain-Derived Neurotrophic Factor/metabolism* ; Fibronectins/metabolism* ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Epilepsy/metabolism* ; Seizures/prevention & control*

OBJECTIVE：To know about the co gnition level and self-medication behavior of antibiotics among urban and rural residents in Lu ’an city of Anhui province ，and to investigate its influential factors and to provide reference for promoting rational use of antibiotics. METHODS ：Totally 684 urban and rural residents aged 18-80 years in Lu ’an city were randomly selected as the research objects by stage sampling method. A self-designed questionnaire was used for household survey ，involving general demographic characteristics ，antibiotics related cognitive level ，antibiotics use behavior and related influential factors ，etc. RESULTS：A total of 657 questionnaires were collected ，with effective rate of 96.1％. Among them ，305 were from urban residents and 352 from rural residents. Among the 657 respondents，38.2％ were male and 61.8％ were female ；their age was （50.30±13.26）years old ；44.7％ of them were educated in primary school or below. 7.8％ of the respondents correctly recognized that antibiotics were not effective to the virus ；12.6％ knew antibiotic resistance ；55.1％ thought that frequent use of antibiotics would reduce the sensitivity of bacteria to it ；23.1％ said they knew the difference between prescription drugs and over-the-counter drugs；58.0％ could tell at least one case of not using antibiotics. For 7 knowledge items ，75.3％ of the residents in the survey area had a total score of less than 3；the cognition level of antibiotics was higher in urban areas and people with higher education level. 66.5％ of the respondents had used antibiotics in the past one year，of which 61.0％ obtained antibiotics by prescription 65161220。E-mail： from doctors ，50.7％ purchased antibiotics by themselves in pharmacies， and 13.1％ used the above two ways both. Among the people who have used antibiotics in the past year ， 81.9％ said they could buy antibiotics without prescription. Among the 657 respondents，49.0％ said that they had to obtain prescription from doctor when taking antibiotics ；68.9％ said that they would stop taking antibiotics when their symptoms improved；19.3％ would increase their dosage in order to enhance the curative effect ；28.3％ would change drugs frequently. Compared with urban residents ，rural residents were more likely to take antibiotics based on prescriptions by physicians [odds ratio （OR）＝1.693，95％ confidence interval （CI）（1.191，2.407）]. The higher the cognitive score ，the lower the behavior rate of having to prescribe antibiotics by doctors [OR ＝0.882，95％CI（0.785，0.991）]，and they were more likely to stop taking antibiotics when symptoms improved [OR ＝1.163，95％CI（1.025，1.319）]，and male were more inclined to increase the dosage of antibiotics to enhance the efficacy [OR ＝1.841，95％CI（1.214，2.792）]. The higher the cognitive score was ，the less likely they were to increase drug dosage to enhance the curative effect [OR ＝0.894，95％CI（0.773，1.034）]，nor were they inclined to change drugs frequently [OR ＝0.873，95％CI（0.767，0.992）]. CONCLUSIONS ：The cognition level to antibiotics of urban and rural residents in Lu ’an city needs to be improved urgently ，and reasonable antibiotic use behavior needs to be standardized. Pure knowledge of antibiotics is not necessarily related to the expected rational drug use behavior. Therefore ，in addition to health promotion for the rational use of drugs for residents ，it is also necessary to create a systematic environment that promotes the rational use of antibiotics and provide residents with multi-channel services for rational use of drugs.

Aim To observe the effects of cytokine signaling inhibition protein-3(SOCS3) on the liver fibrosis progression and reverse.Methods C57BL/6 mouse model was established by subcutaneous injection of carbon tetrachloride(CCl4).After a successful model of fibrosis, one-month normal diet was given to induce the reverse fibrosis model, while normal mice of the same gender and weight were as control group.Mice were sacrificed at 1, 2, 3, 4, 5, 6, 7, 8 weeks, respectively, then the liver tissue was harvested for the observation of its injury by hematoxylin and eosin(HE) staining.Then Masson staining was applied for the detection of changes in collagen, and the immunohistochemistry(IHC) for the observation of type Ⅰ Collagen(Colla-1), alpha smooth muscle actin(α-SMA), transforming growth factor beta 1(TGF-β1) and SOCS3 protein expression.In vitro formation of fibrosis was induced by TGF-β1 stimulating HSC-T6 cell lines, which was then reversed by MDI medium, with co-incubation of HSC-T6 cells with plasmid in the process of the reverse.Western blot was employed to detect SOCS3, Colla-1, α-SMA, TGF-β1 expression.Results The expression of SOCS3 and TGF-β1 increased in mouse model of fibrosis with the worsening fibrosis process and decreased in the reverse process.Over-expression SOCS3 in the reverse process reduced the development of liver fibrosis;meanwhile, the expression of TGF-β1 was also reduced accordingly.Conclusion SOCS3 may influence the development of the liver fibrosis and its reverse via regulating the expression of TGF-β1.

Objective We sought to determine whether SF3a3 was capable of inhibiting HCV replication and to investigate the possible mechanisms.Methods Using the infectious HCV clones JFH1, we performed siRNA knockdown in Huh7.5.1 cells.First, we performed small interfering RNA (siRNA) to knock down SF3 gene expression.After 72 h incubation, Huh7.5.1 cells were infected with JFH1 for 24 h and then treated with 30IU/ml PEG-IFNα-2b for 48h.Members of SF3 family, HCV core and the key proteins of the IFN relative pathways were monitored by real time PCR and Western blot.Results SF3a3 mRNA level and protein expression were significantly decreased by SF3a3 specific siRNA compared with non-targeting siRNA, whose silencing effect was the best compared with other members of SF3a3 family;knockdown of SF3a3 protein expression by siRNA rescued HCV core expression, inhibited the role of interferon in anti-HCV infection under the same PEG-IFNα-2b pressure, and downregulated the phosphorylation of PI3K and Akt, as well as their total protein levels.Conclusions Silencing SF3a3 by specific siRNA could downregulate the expression of PI3K-Akt and p-PI3K/p-Akt proteins, which promoted the HCV replication.