Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Alzheimer's disease (AD) is a central nervous system degenerative disease that is prone to occur in the pre-senile period and senile period . It is characterized by behavioral impairment and progressive cognitive impairment, with an insidious onset and progressive aggravation. It not only has cognitive decline, but also is accompanied by other neurological and psychiatric symptoms. Memory loss is the core symptom of the disease. Diabetes mellitus (DM) is a disease characterized by hyperglycemia. In recent years, with the increasing incidence of the two diseases, more and more studies have reported the correlation between AD and DM. This article reviews the correlation between AD and DM from the aspects of correlation research, pathological mechanism and drug treatment through the review of relevant literature, with a view to providing guidance for clinical practice.

Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.

Cirrhotic portal hypertension could complicate impaired intestinal barrier function,small intestinal bacterial overgrowth and dysbiosis of intestinal microbiota,further exacerbate the severity of cirrhosis.TIPS might lead to hepatic encephalopathy(HE).The research progresses in correlations of cirrhotic portal hypertension,TIPS related HE and gut microbiota were reviewed in this article.

Objective To analyze the current status of dyslipidemia among employees in a petrochemical enterprise and its influencing factors. Methods A total of 1 636 employees from a petrochemical enterprise were selected as the research subjects by the judgment sampling method. Peripheral venous blood was collected from the research subjects to detect total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low- density lipoprotein cholesterol (LDL-C) in serum. The Effort-Reward Imbalance (ERI) Questionnaire was used to investigate occupational stress in the ERI model. Results The detection rate of dyslipidemia among the research subjects was 52.7%. The detection rates of abnormal total cholesterol, triglyceride, LDL-C, and HDL-C were 35.7%, 31.4%, 24.3%, and 10.0%, respectively. The detection rate of high occupational stress among the research subjects was 26.3%. The result of multivariate logistic regression analysis showed that the risks of dyslipidemia in overweight and obese employees were higher than that of normal body mass [ odds ratio (OR) and 95% confidence interval (CI) were 2.111 (1.692-2.634) and 2.346 (1.591-3.458), both P<0.01]. The risk of dyslipidemia in lean body mass employees was lower than those with normal body mass [OR (95%CI) was 0.130 (0.030-0.564), P<0.05]. The risk of dyslipidemia in smokers was higher than that in non-smokers [OR (95%CI) was 1.462 (1.124-1.902), P<0.01]. Employees with 20-30 years and ≥ 30 years of service had higher risks of dyslipidemia than those with <10 years of service [OR (95%CI) were 1.411 (1.038-1.919) and 1.869 (1.202-2.906), respectively, both P<0.05]. The risk of dyslipidemia among employees with high effort level of occupational stress in ERI model was higher than those with low effort level [OR (95%CI) was 1.351(1.045-1.745), P<0.05]. Conclusion Dyslipidemia prevalence is relatively high among the petrochemical enterprise employees. Overweight, obesity, smoking, long service years, and occupational stress in ERI model are influencing factors of dyslipidemia. To prevent dyslipidemia, it is necessary to strengthen blood lipid monitoring and lifestyle intervention in personnel with overweight, obesity, smoking, long service years, and occupational stress in ERI model.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Objective: This study aimed to translate the English version of the Perceived Competence Scale for Disaster Mental Health Workforce (PCS-DMHW) into Chinese, and to test its reliability and validity in Chinese mental health workers. Methods: With the consent of Professor Choi, Keimyung University, Korea, and the authorization of the scale, the English version of PCS-DMHW was translated, retranslated and culturally debugged to form the Chinese version of PCS-DMHW. The general information questionnaire and the Chinese version of PCS-DMHW scale were used to investigate 706 mental health workforce from 9 tertiary hospitals in Sichuan province in China from March 24, 2020 to April 14, 2020. The Cronbach’s α coefficient was used to evaluate the internal consistency reliability of the scale, and the test-retest correlation coefficient r was used to evaluate the test-retest reliability of the scale. The content validity indexes (CVI) and exploratory factor analysis (EFA) was used separately for evaluating the content validity and structure validity of the scale. Results: The Cronbach’s α coefficient of the Chinese version of PCS-DMHW total scale, individual competences and organizational competences subscale was 0.978, 0.956, and 0.964, respectively. The test-retest reliability of the total scale, individual competences and organizational competences subscale was 0.949, 0.932 and 0.927, respectively. The item-level CVI of all scale were ranged from 0.833–1.000, the scale-level CVI (S-CVI)/universal agreement of the total scale, individual competences and organizational competences subscale was 0.833, 0.875, and 0.857, respectively, and the S-CVI/average was 0.972, 0.979, and 0.976, respectively. EFA showed that two principal components were extracted from the subscale of individual competences and organizational competences. Conclusion The Chinese version of PCS-DMHW has good reliability and validity, and can be widely used in China.

Objective:To explore the value of a nomogram model based on the CT enterography (CTE) signs for prediction of intestinal penetrating lesions in patients with Crohn disease (CD).Methods:The clinical and CTE data of CD patients who underwent at least two CTE examinations from January 2010 to June 2020 in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. A total of 112 patients were enrolled, and according to whether there was intestinal wall penetration in the last CTE observation were divided into non-penetration group (84 cases) and penetration group (28 cases). First, the clinical and CTE data for the first examination was analyzed by using univariate and multivariate Cox proportional hazards regression to screen out high-risk factors that could effectively predict intestinal wall penetrating lesions in CD patients and established a nomogram model. Then the change trend of CTE data (ΔCTE) between the first and last clinical and CTE signs was analyzed by using univariate and multivariate Cox proportional hazards regression, and built a nomogram model to sort out ΔCTE that may accompany the development of penetrating lesions in CD patients. The Harrell concordance index was used to evaluate the discriminative ability of the nomogram model.Results:In the first time clinical and CTE signs, multivariate Cox proportional hazards regression results showed that numbers of diseased bowel segments (HR=0.686, 95%CI 0.475-0.991, P=0.045) and the shortest diameter of the largest lymph node (HR=0.751, 95%CI 0.593-0.949, P=0.017) were independent protection factors for penetrating lesions, and rough bowel wall surface (HR=5.626, 95%CI 2.466-12.839, P<0.001) was an independent risk factor for penetrating lesions. The specificity and sensitivity of the nomogram model to predict non-penetration lesions were 82.1% and 59.5% respectively, and the Harrell concordance index was 0.810 (95%CI 0.732-0.888). In the ΔCTE signs, multivariate Cox proportional hazards regression showed that Δrough bowel wall surface (always rough bowel wall surface HR=12.344, 95%CI 2.042-74.625, P=0.006; slide bowel wall surface becomes rough bowel wall surface HR=28.720, 95%CI 4.580-180.112, P<0.001) and Δthe shortest diameter of the largest lymph node (HR=1.534, 95%CI 1.091-2.157, P=0.014) were independent risk factors for penetrating lesions. The specificity and sensitivity of the nomogram model were 89.3% and 79.2% respectively, and the Harrell concordance index was 0.876 (95%CI 0.818-0.934). Conclusion:The nomogram based on CTE signs of numbers of diseased bowel segments, the shortest diameter of the largest lymph node and rough bowel wall surface and ΔCTE can effectively predict the intestinal wall penetrating lesions of CD patients.

Early diagnosis of pulmonary diseases is of great significance for their prevention and treatment. Serum Krebs von den Lungen-6 (KL-6) assay can reflect the damage degree of alveolar epithelium and stromal tissue, and is simple, non-invasive and low-cost. Pervious study showed that the serum KL-6 level was higher in patients with various interstitial lung diseases (e.g. idiopathic pulmonary fibrosis and connective tissue disease, primary Sjögren's syndrome, rheumatoid arthritis, idiopathic inflammatory myopathy and systemic sclerosis combined with interstitial lung disease), non-small cell lung cancer, various pneumonias and chronic obstructive pulmonary disease compared to healthy controls. Therefore, serum KL-6 has good sensitivity and specificity for the early diagnosis of these diseases. Occupational pneumoconiosis is an interstitial lung disease with a well-established etiology. Pervious study has shown that serum KL-6 level was higher in patients with occupational silicosis, occupational asbestosis, and dust-exposed workers compared to healthy controls. However, due to the limited sample size and the inconsistent findings on different studies, further research is needed to study the role of serum KL-6 in the early diagnosis of pneumoconiosis. Future studies should increase the sample size, improve the detection methods for serum KL-6, explore its feasibility as an early diagnostic biomarker for occupational pulmonary diseases, and investigate the efficacy andvalue of its combined application with other biomarkers in the early diagnosis of various pulmonary diseases, including occupational lung diseases, to fully exploit its predictive role in pulmonary diseases.

Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG _FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG _EXP (the mean absolute deviations | Δ G FEP - Δ G EXP |  < 2 kcal/mol) than those ΔG _MM-PBSA or ΔG _MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC₅₀ of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.