BackgroundThe violent aggressive behaviors of patients with schizophrenia usually have the characteristics of suddenness， unpredictability， high severity， and great difficulty in prevention. Early identification and accurate assessment of their risk of violent aggression have significant clinical significance. ObjectiveTo construct a predictive model for the violence risk in hospitalized patients with schizophrenia， to identify the key factors influencing the occurrence of violent behavior in these patients， so as to provide references for clinical precise quantitative assessment and early intervention. MethodsA total of 200 patients with schizophrenia who were hospitalized at Taiyuan Psychiatric Hospital from March 2022 to September 2024 and met the diagnostic criteria of the International Classification of Diseases， eleventh edition （ICD-11） were collected to form the modeling cohort. They were randomly divided into a training set （n=140） and a test set （n=60） at a ratio of 7∶3. Based on the least absolute shrinkage and selection operator （LASSO） regression algorithm， the feature variables were screened and dimension-reduced. The support vector machine （SVM） from machine learning was selected for model training and prediction. The discrimination efficacy of the model was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）， accuracy， precision， sensitivity， specificity， F1 value， and Brier value. ResultsLASSO regression screening identified 16 feature variables. Pearson correlation analysis revealed a positive correlation between prior violent behavior frequency and clinical psychiatric symptom scores （r=0.580， P<0.01）， a positive correlation between hospitalization compliance and current disease status （r=0.550， P=0.003）， and a positive correlation between educational level and family per capita monthly income （r=0.367， P<0.01）. The SVM model achieved an AUC of 0.853， accuracy of 0.800， precision of 0.810， sensitivity of 0.895， specificity of 0.636， F1 value of 0.850， and Brier value of 0.168. ConclusionThe SVM model has a relatively high level of applicability and overall predictive performance in the assessment of violent risk in schizophrenia patients， which is helpful for the early identification of violent risks in such patients. ［Funded by Specialized Research Project for Enhancing the Competence of Health Professionals in Taiyuan City （number， Y2023006）］

ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin Ⅰ(ISP Ⅰ)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP Ⅰ in protecting against liver fibrosis.According to our results,ISP Ⅰ not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP Ⅰ.ISP Ⅰ through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carri-mycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides po-tential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.

Targeted covalent inhibitors,primarily targeting cysteine residues,have attracted great attention as potential drug candidates due to good potency and prolonged duration of action.However,their dis-covery is challenging.In this research,a database-assisted liquid chromatography-tandem mass spec-trometry(LC-MS/MS)strategy was developed to quickly discover potential cysteine-targeting compounds.First,compounds with potential reactive groups were selected and incubated with N-acetyl-cysteine in microsomes.And the precursor ions of possible cysteine-adducts were predicted based on covalent binding mechanisms to establish in-house database.Second,substrate-independent product ions produced from N-acetyl-cysteine moiety were selected.Third,multiple reaction monitoring scan was conducted to achieve sensitive screening for cysteine-targeting compounds.This strategy showed broad applicability,and covalent compounds with diverse structures were screened out,offering structural resources for covalent inhibitors development.Moreover,the screened compounds,norket-amine and hydroxynorketamine,could modify synaptic transmission-related proteins in vivo,indicating their potential as covalent inhibitors.This experimental-based screening strategy provides a quick and reliable guidance for the design and discovery of covalent inhibitors.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

Objective:To investigate the sero-conversion rate of HIV antibody and influencing factors in cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture(Dehong).Methods:A cohort design was used to recruit HIV-negative people in cross-border couples in Dehong in 2017. Follow-up was conducted in 2023, and questionnaire survey and HIV test were carried out to calculate the sero-conversion rate of HIV antibody. Univariate and multivariate logistic regression models were used to analyze the influence factors for HIV infections.Results:A total of 36 278 HIV-negative persons in cross-border couples were included in the 2017 baseline survey, of whom 22 438 (61.9%) were tested in follow-up in 2023. The sero-conversion rate between 2017 and 2023 was 0.51% (115/22 438). Multivariate logistic regression analysis showed that length of marriage <6 years, Jingpo ethnic group, education level of primary school or below, drug use, illegal marriage and HIV infected spouse were the risk factors of HIV infection in male spouses, and length of marriage <6 years, Jingpo ethnic group, illegal marriage and HIV infected spouse were the risk factors in female spouses.Conclusions:The sero-conversion rate of HIV antibody in cross-border couples in Dehong was relatively high. HIV infection was mainly caused by secondary transmission in the couples, and men might also be infected through drug use. It is necessary to strengthen the registration and management of cross-border couples, especially the couples with discordant HIV infection status, and the intervention in drug users to reduce the risk for secondary transmission of HIV in the cross-border couples.

Objective:To describe the prevalence of non-alcoholic fatty liver disease (NAFLD) in people living with HIV in Taizhou, Zhejiang Province, and identify the factors associated with NAFLD in this population.Methods:A cross-sectional survey was conducted from 2021 to 2023. Based on the routine follow-up management of people living with HIV, liver ultrasound examination, physical examination and laboratory test were conducted to collect the information about the diagnosis of NAFLD and biochemical indicators in this population. Logistic regression model was used to identify the factors associated with the prevalence of NAFLD.Results:In the 2 550 study participants, the prevalence of NAFLD was 21.5% (548/2 550), abnormal liver function was found in 23.7% (604/2 550) of the study participants, and liver fibrosis was found in 45.2% (1 152/2 550) of the study participants. Multivariable logistic regression analyses showed that being women (a OR=0.55, 95% CI: 0.42-0.73), being overweight or obese (a OR=3.22, 95% CI: 2.59-4.01), having diabetes (a OR=3.37, 95% CI: 2.15-5.29), having dyslipidemia (a OR=2.96, 95% CI: 2.25-3.89), CD4 + T lymphocyte (CD4) counts <200 cells/μl (a OR=0.61, 95% CI: 0.42-0.88), and receiving Efavirenz (EFV) + Lamivudine (3TC) + Zidovudine (AZT) for antiretroviral therapy (ART)(a OR=1.52, 95% CI: 1.17-1.98) were associated with NAFLD. NAFLD was positively associated with abnormal liver function (a OR=2.01, 95% CI: 1.60-2.52) and inversely associated with liver fibrosis (a OR=0.76, 95% CI: 0.59-0.98). The 45-59 age group (a OR=7.05, 95% CI: 5.65-8.80), CD4 counts <200 cells/μl (a OR=1.45, 95% CI: 1.06-1.97) and receiving Nevirapine (NVP)+3TC+AZT of ART (a OR=1.87,95% CI: 1.44-2.43) were the main factors associated with liver fibrosis. Conclusions:The prevalence of NAFLD in people living with HIV Taizhou was more than 20.0%, with a significant proportion of them having abnormal liver function and liver fibrosis. Being overweight or obese, suffering from diabetes, having dyslipidemia, low CD4 counts, and receiving specific ART were associated with NAFLD. NAFLD, CD4 counts and specific ART were the main factors associated with abnormal liver function and liver fibrosis.