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.

Objective To characterize neurological alterations associated with structural bowel damage in patients with Crohn's disease(CD)through radiomics-assisted neurophenotyping,utilizing multiparametric brain MRI.Methods This prospective study enrolled patients with CD who underwent brain MRI,MR enterography,and ileocolonoscopy within one week.The Lémann Index was used to quantitatively assess cumulative structural bowel damage.CD patients were stratified into two groups based on a cutoff value of 4.8:those with bowel damage(LI>4.8)and those without bowel damage(LI≤4.8).A neurophenotype model was developed to characterize the neural changes associated with bowel damage in CD.Key features were selected from first-order features extracted from multiparametric brain MRI in the training cohort and validated in an independent test cohort.Results The final study population comprised 109 patients,including 51 individuals with bowel damage and 58 without bowel damage.The neurophenotype model scores were 0.785(95%CI:0.506～0.945)in the bowel damage group and 0.155(95%CI:0.093～0.394)in the non-bowel damage group,showing a statistically significant difference between the two groups(P<0.001).The developed model exhibited strong discriminative performance,with area under the receiver operating characteristic curve(AUC)values ranging from 0.824 to 0.918 across the training,vali-dation,and test cohorts(all P<0.05).Conclusion Our radiomics-assisted neurophenotype analysis reveals neural alterations in CD patients with bowel damage,which may indicate extraintestinal manifestations associated with cumulative intestinal injury.

Hereditary angioedema(HAE)is a rare autosomal dominant disorder characterized by recur-rent,unpredictable episodes of skin and mucosal edema,which may affect the face,extremities,respiratory tract,gastrointestinal tract,and genitals,with a global prevalence of approximately 1 in 50 000.This case re-port presents a young female patient with a history of recurrent abdominal pain and multisite edema.During an acute episode,laboratory tests revealed decreased complement C4 levels along with reduced concentration and function of C1 esterase inhibitor.Computed tomography(CT)demonstrated bowel wall edema and pelvic effu-sion.Previously undiagnosed,the patient was admitted for this acute attack and was ultimately diagnosed with HAE following a multidisciplinary treatment(MDT)team discussion at our hospital.The rapid diagnosis and treatment of this case highlight the critical role of MDT in the management of complex and rare diseases.

Objective To characterize neurological alterations associated with structural bowel damage in patients with Crohn's disease(CD)through radiomics-assisted neurophenotyping,utilizing multiparametric brain MRI.Methods This prospective study enrolled patients with CD who underwent brain MRI,MR enterography,and ileocolonoscopy within one week.The Lémann Index was used to quantitatively assess cumulative structural bowel damage.CD patients were stratified into two groups based on a cutoff value of 4.8:those with bowel damage(LI>4.8)and those without bowel damage(LI≤4.8).A neurophenotype model was developed to characterize the neural changes associated with bowel damage in CD.Key features were selected from first-order features extracted from multiparametric brain MRI in the training cohort and validated in an independent test cohort.Results The final study population comprised 109 patients,including 51 individuals with bowel damage and 58 without bowel damage.The neurophenotype model scores were 0.785(95%CI:0.506～0.945)in the bowel damage group and 0.155(95%CI:0.093～0.394)in the non-bowel damage group,showing a statistically significant difference between the two groups(P<0.001).The developed model exhibited strong discriminative performance,with area under the receiver operating characteristic curve(AUC)values ranging from 0.824 to 0.918 across the training,vali-dation,and test cohorts(all P<0.05).Conclusion Our radiomics-assisted neurophenotype analysis reveals neural alterations in CD patients with bowel damage,which may indicate extraintestinal manifestations associated with cumulative intestinal injury.

Hereditary angioedema(HAE)is a rare autosomal dominant disorder characterized by recur-rent,unpredictable episodes of skin and mucosal edema,which may affect the face,extremities,respiratory tract,gastrointestinal tract,and genitals,with a global prevalence of approximately 1 in 50 000.This case re-port presents a young female patient with a history of recurrent abdominal pain and multisite edema.During an acute episode,laboratory tests revealed decreased complement C4 levels along with reduced concentration and function of C1 esterase inhibitor.Computed tomography(CT)demonstrated bowel wall edema and pelvic effu-sion.Previously undiagnosed,the patient was admitted for this acute attack and was ultimately diagnosed with HAE following a multidisciplinary treatment(MDT)team discussion at our hospital.The rapid diagnosis and treatment of this case highlight the critical role of MDT in the management of complex and rare diseases.

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.

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.