ObjectiveTo investigate the molecular mechanism of kaempferol-induced apoptosis in hepatic stellate cells （HSC） via the mitochondrial pathway. MethodsHSC were divided into five groups： blank control， transforming growth factor-β1（TGF-β1） （10 ng/mL） group， and groups treated with different concentrations of kaempferol （8， 16， 32 µmol/L）. Cell counting kit-8（CCK-8） assay was used to evaluate chrysin's effect on HSC proliferation. Transwell assay was used to assess chrysin's impact on HSC migration. Flow cytometry was used to detect apoptosis， reactive oxygen species （ROS） expression， and mitochondrial permeability transition pore （mPTP） opening across groups. 5，5′，6，6′-Tetrachloro-1，1′，3，3′-tetraethylimidacarbocyanine iodide （JC-1） assay was used to test mitochondrial membrane potential. Western blot analysis was performed to determine the expression levels of mitochondrial apoptosis-associated proteins， namely B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Cleaved-Caspase3， Cleaved-Caspase9， and sirtuin 3 （SIRT3）. Transmission electron microscopy was used to examine mitochondrial structural alterations. Molecular docking and kinetic simulations were used to analyze the targeted interaction between kaempferol and NAD-dependent deacetylase sirtuin-3 （SIRT3）. ResultsCompared with the blank control group： in the TGF-β1 group， HSC proliferation and migration rates increased （P<0.01）， ROS levels and mPTP opening both increased （P<0.05）， the JC-1 red/green fluorescence ratio increased （P<0.01）， and the expression of Cleaved-Caspase-3， Cleaved-Caspase-9 and Bcl-2 increased （P<0.05）， whilst SIRT3 expression decreased （P<0.01）； the number of mitochondria increased （P<0.05）， and mitochondrial length decreased （P<0.01）. Compared with the TGF-β1 group： treatment with all groups of kaempferol reduced HSC proliferation and migration rates （P<0.01）， whilst simultaneously increasing the HSC apoptosis rate （P<0.01）； HSC ROS levels and mPTP opening both increased （P<0.05）； the JC-1 red/green fluorescence ratio decreased （P<0.01）， and the expression levels of Bax， Cleaved-Caspase-3 and Cleaved-Caspase-9 were upregulated （P<0.01）， whilst the expression levels of Bcl-2 and SIRT3 were downregulated （P<0.01）， and the number of mitochondria increased （P<0.05）； mitochondrial length was reduced （P<0.01）. Molecular docking and dynamics simulations revealed that the docking energy for kaempferol with SIRT3 was 108.89 kcal/mol； the RMSD curve stabilized after 20 ns； and RMSF analysis indicated that most residues exhibited minimal fluctuations. ConclusionKaempferol induces HSC apoptosis through the mitochondrial pathway， potentially via targeting SIRT3 and disrupting mitochondrial function.

Chronic liver diseases with common causes including viral infections， alcohol abuse， and autoimmune diseases. Alkaloids， as a class of plant-derived compounds， have shown significant potential in regulating chronic liver diseases. Recent studies have shown that alkaloids are able to exert a therapeutic effect on chronic liver diseases through multiple pathways. These compounds have a regulatory effect on key pathological processes such as liver fibrosis， inflammatory response， oxidative stress， and cell apoptosis， and they also regulate the metabolic homeostasis of hepatocytes by modulating multiple signaling pathways， thereby playing a role in regulating chronic liver diseases. This article reviews the role and mechanism of alkaloids in the treatment of chronic liver diseases， in order to provide new ideas and directions for the treatment of chronic liver diseases.

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

Objective:To investigate the efficacy, safety and recurrence rate of oral atenolol in the treatment of infantile hemangioma, so as to provide evidence-based medicine basis and reference for clinic.Methods:Search on the following public databases from January 1, 2008 to June 13, 2022: Web of Science, PubMed, Cochrane Library, Embase, U. S. National Library of Medicine Clinical Trials Registry Platform; China National Knowledge Infrastructure(CNKI), Chinese Biomedical Literature Service System(SinoMed), Chinese Science and Technology Journal Database and Wanfang Data. According to inclusion and exclusion criteria, studies on oral atenolol for the treatment of infantile hemangioma were selected. The outcome indicators were efficiency (complete response rate), incidence of adverse effects and recurrence rate. The single-arm meta-analysis was performed using R software version 4.1.2. Egger’s test was employed and funnel plots were drawn to assess publication bias in the literature.Results:A total of 14 studies were included, comprising 5 randomized controlled trials, 5 single-arm studies, 3 non-randomized controlled trials, and 1 case-control study. The oral administration of atenolol for the treatment of infantile hemangiomas resulted in an efficacy rate (complete remission rate) of 62% (95% CI 52%~71%). The incidence rate of adverse reactions related to the digestive system was 18% (95% CI 7%~30%), while that related to β2 receptor blockade was 4% (95% CI 2%~6%), central nervous system-related adverse reactions occurred at a rate of 10% (95% CI 5%~16%), the recurrence rate was 5% (95% CI 2%~9%). Egger’s test indicated that there was no significant publication bias in the efficacy rate, central nervous system-related adverse reaction rate, and gastrointestinal-related adverse reaction rate of oral atenolol treatment for infantile hemangiomas ( P>0.05). The sensitivity analysis for the efficacy rate, adverse reaction rate, and recurrence rate of oral atenolol treatment for infantile hemangiomas suggested that the result were stable and reliable. Conclusion:Oral administration of atenolol for the treatment of infantile hemangiomas demonstrates significant efficacy, fewer adverse reactions, and a low recurrence rate, making it a promising candidate as a reasonable alternative to oral propranolol for treating infantile hemangiomas.

Objective:To investigate the efficacy, safety and recurrence rate of oral atenolol in the treatment of infantile hemangioma, so as to provide evidence-based medicine basis and reference for clinic.Methods:Search on the following public databases from January 1, 2008 to June 13, 2022: Web of Science, PubMed, Cochrane Library, Embase, U. S. National Library of Medicine Clinical Trials Registry Platform; China National Knowledge Infrastructure(CNKI), Chinese Biomedical Literature Service System(SinoMed), Chinese Science and Technology Journal Database and Wanfang Data. According to inclusion and exclusion criteria, studies on oral atenolol for the treatment of infantile hemangioma were selected. The outcome indicators were efficiency (complete response rate), incidence of adverse effects and recurrence rate. The single-arm meta-analysis was performed using R software version 4.1.2. Egger’s test was employed and funnel plots were drawn to assess publication bias in the literature.Results:A total of 14 studies were included, comprising 5 randomized controlled trials, 5 single-arm studies, 3 non-randomized controlled trials, and 1 case-control study. The oral administration of atenolol for the treatment of infantile hemangiomas resulted in an efficacy rate (complete remission rate) of 62% (95% CI 52%~71%). The incidence rate of adverse reactions related to the digestive system was 18% (95% CI 7%~30%), while that related to β2 receptor blockade was 4% (95% CI 2%~6%), central nervous system-related adverse reactions occurred at a rate of 10% (95% CI 5%~16%), the recurrence rate was 5% (95% CI 2%~9%). Egger’s test indicated that there was no significant publication bias in the efficacy rate, central nervous system-related adverse reaction rate, and gastrointestinal-related adverse reaction rate of oral atenolol treatment for infantile hemangiomas ( P>0.05). The sensitivity analysis for the efficacy rate, adverse reaction rate, and recurrence rate of oral atenolol treatment for infantile hemangiomas suggested that the result were stable and reliable. Conclusion:Oral administration of atenolol for the treatment of infantile hemangiomas demonstrates significant efficacy, fewer adverse reactions, and a low recurrence rate, making it a promising candidate as a reasonable alternative to oral propranolol for treating infantile hemangiomas.

Acute pancreatitis (AP) is a severe disease with an increasing incidence rate in clinical practice. Although most patients have mild pancreatitis, the fatality rate of severe pancreatitis remains at a relatively high level, and therefore, early-stage, simple, and accurate clinical scoring systems are urgently needed to determine the severity of AP, so as to facilitate effective disease management and symptomatic treatment and reduce the fatality rate of patients. At present, a large number of studies have demonstrated that the scoring systems such as Ranson score, APACHE Ⅱ score, BISAP score, CTSI score, and some serological markers have been used to evaluate the severity and prognosis of AP, but all of them have certain limitations. This article reviews the research advances in the existing scoring systems, single serological markers, and related modified scoring systems in recent years. Through a literature review, it is concluded that there is no a single scoring system or a single indicator that can cover the whole process of AP diagnosis and treatment and accurately judge the severity of AP, and therefore, it is necessary to develop a new scoring system or combine various indicators for comprehensive evaluation.

Objective:To investigate the clinical effect of drugs combined with hyperbaric oxygen（HBO）on nervous system damage caused by nitrous oxide（N 2O）poisoning. Methods:The clinical data of 12 patients with nerve damage caused by N 2O poisoning admitted to the Department of Neurology，Hyperbaric Oxygen of a certain PLA hospital from February 2020 to April 2021 were reviewed. The changes of neuroelectrophysiological and neurological functions of patients before and after treatment were analyzed using electroneurogram detection，Berg balance scale，and Holden’s functional ambulation categories（FAC）as observation indicators. Results:After drug treatment combined with HBO，the motor conduction velocity，sensory conduction velocity，motor latency，motor evoked potential，and sensory evoked potential of electroneurogram of 12 patients were significantly improved，and the differences were statistically significant（ P < 0.05）.Berg balance scale scores were significantly improved compared with those before treatment，and the differences were statistically significant（ P < 0.05）.FAC scale was improved compared with before treatment，but the difference was not statistically significant（ P > 0.05）. Conclusion:HBO combined with folic acid，vitamin B12 and other neurotrophic drugs has a certain clinical effect in the treatment of nerve damage caused by N 2O poisoning，which is worthy of further study and improvement.

Objective:To investigate the clinical effect of drugs combined with hyperbaric oxygen（HBO）on nervous system damage caused by nitrous oxide（N 2O）poisoning. Methods:The clinical data of 12 patients with nerve damage caused by N 2O poisoning admitted to the Department of Neurology，Hyperbaric Oxygen of a certain PLA hospital from February 2020 to April 2021 were reviewed. The changes of neuroelectrophysiological and neurological functions of patients before and after treatment were analyzed using electroneurogram detection，Berg balance scale，and Holden’s functional ambulation categories（FAC）as observation indicators. Results:After drug treatment combined with HBO，the motor conduction velocity，sensory conduction velocity，motor latency，motor evoked potential，and sensory evoked potential of electroneurogram of 12 patients were significantly improved，and the differences were statistically significant（ P < 0.05）.Berg balance scale scores were significantly improved compared with those before treatment，and the differences were statistically significant（ P < 0.05）.FAC scale was improved compared with before treatment，but the difference was not statistically significant（ P > 0.05）. Conclusion:HBO combined with folic acid，vitamin B12 and other neurotrophic drugs has a certain clinical effect in the treatment of nerve damage caused by N 2O poisoning，which is worthy of further study and improvement.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.