Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Bismuth iodide(BiOI)with different crystal plane ratios of(110)to(001)was synthesized,and typeⅡheterojunction formed between(001)and(110)crystal planes of BiOI was used to improve the separation efficiency of photogenerated electrons and holes.Then the BiOI(001)/(110)was composited with nitrogen-doped graphene quantum dots(N-GQDs)to prepare a ternary composites,which could enhance the range and intensity of light absorption,and prolonged the lifetime of photogenerated electrons due to the formation of Z-scheme heterojunctions between BiOI and N-GQDs,thereby leading to the excellent photoelectric performance of the BiOI/N-GQDs for generating sensitive photoelectric response signals.A photoelectrochemical sensor for sensitive detection of chlorpyrifos(CPF)was designed with BiOI/N-GQDs-modified FTO electrode as a photocathode.The S and N atoms contained in CPF were coordinated with Bi(Ⅲ)on the surface of BiOI,which reduced the photocurrent of BiOI/N-GQDs.The photocurrent change was linear with logarithm of concentration of CPF in the range of 1.5×10-12-5.0×10-9 mol/L,and the detection limit was 1.5×10-12 mol/L.The sensor was highly sensitive,selective and stable,and could be used for determination of trace CPF in environmental and food samples.

Objective:To review the application of internet cognitive behavioral therapy (CBT) in perinatal women with negative emotions, point out the limitations of existing studies, and put forward development suggestions for future research.Methods:Using the Scope review guide published by Joanna Briggs Institute as the methodological framework, eight Chinese and English databases including China National Knowledge Infrastructure (CNKI), Wanfang, PubMed and Web of Science were searched until July 1, 2024, and the literatures were collected and analyzed.Results:A total of 18 literatures were included. The interventionists of internet cognitive behavioral therapy were mostly psychologists; the intervention methods were mostly in the form of partial participation of therapists, and the intervention platforms were mostly websites. The intervention content was centered on mental health education, emotional monitoring, cognitive reconstruction, behavioral activation training, and problem solving. There were 15 studies that demonstrated that internet cognitive behavioral therapy was effective, and three studies showed that internet cognitive behavioral therapy was not effective in improving negative emotions in perinatal women, but perinatal women responded to treatment.Conclusions:The Internet cognitive behavioral therapy can effectively improve the negative emotions of perinatal pregnant women, but the long-term effect is not clear. Future studies can expand the sample size and follow up the effect for a long time.

AIM:To investigate the effects of early high-fat diet(HFD)on cognitive function and hippocam-pal lipidomic profile in transgenic mice bearing five familial Alzheimer disease mutant genes(5×FAD).METHODS:Eight-week-old SPF grade female wild-type(WT)mice were used as the contorl group,and 5×FAD mice were randomly divided into model(5×FAD)group and 5×FAD+HFD group,with 10 mice in each group.The 5×FAD+HFD group was orally given high-fat chow and the remaining 2 groups were given control chow for 12 weeks,and the change in body weight of the mice were recorded.Y-maze and Morris water maze tests were performed to measure the learning memory ability of the mice.Serum total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)levels were measured using a biochemical analyzer.Immunohistochemistry was per-formed to visualize amyloid β-protein(Aβ)plaques in brain tissues.Hippocampal levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,and Aβ were measured by enzyme-linked immunosorbent assay(ELISA).Non-tar-geted lipidomic technology was used to measure the changes of hippocampal lipids.RESULTS:Compared with WT group,the mice in 5×FAD group lost significantly less weight(P<0.01)and spent significantly less time exploring the new arm of the Y-maze and the target quadrant of the water maze(P<0.05 or P<0.01).Brain Aβ plaques were significant-ly increased(P<0.01).Hippocampal levels of Aβ1-40,Aβ1-42,IL-1β and TNF-α were significantly elevated(P<0.05 or P<0.01).Compared with the 5×FAD group,the mice in the 5×FAD+HFD group showed significant increase in body weight(P<0.01)and time spent exploring the new arm of the Y-maze and the target quadrant of the water maze(P<0.01).Biochmeical analysis showed serum TC,LDL-C,HDL-C levels and HDL/TC ratio were significantly increased(P<0.05).Brain Aβ plaques were significantly reduced(P<0.05)and hippocampal Aβ1-40,Aβ1-42 and IL-1β levels were sig-nificantly decreased(P<0.05).Compared with the WT group,27 lipids were increased and 9 lipids were decreased in the 5×FAD group,involving the pathways such as cholesterol metabolism,fat digestion and absorption,regulation of lipolysis processes in adipocytes,and glycerophospholipid metabolism.Eighteen lipids were increased and 47 lipids were de-creased in the 5×FAD+HFD group compared to the 5×FAD group.Cardiolipin and TG were important lipids for separating the lipid profiles of the WT and 5×FAD groups,and TG was an important lipid for separating the lipid profiles of the 5×FAD and 5×FAD+HFD groups.Differential lipid enrichment analysis showed significant increase in TG lipid in the 5×FAD group compared with the WT group and significant decrease in TG lipid in the 5×FAD+HFD group compared with the 5×FAD group.CONCLUSION:Early HFD ameliorates cognitive function in 5×FAD mice by modifying TG metabolic disorder and attenuating neuroinflammation.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Removal of endogenic renal sinus tumors which are located at the renal hilum,is recognized as one of the most challenging surgeries in urology due to the complex anatomical structure.With the help of the high-definition field of vision and flexible robotic arms of the Da Vinci robot system,our team have carried out precision intra-sinus tumor enucleation based on preoperative interactive qualitative and Interactive Quantitative Quality Assurance for 3D Imaging(IQQA-3D)accurate reconstruction technology,as well as the clinical anatomical characteristics of patients with renal sinus tumors.During operation,the renal pedicle is fully dissected,the perihilar fat is cleared,and the tumor capsule is exposed.Subsequently,the blood supply to the kidney is blocked,and the tumor is precisely excised along the tumor capsule.The vascular stumps are sutured point-to-point,and the wound is closed and locked.After the blood supply restores,regional arterial occlusion is performed if necessary to ensure the safety of the surgery and maximize the preservation of renal function.This article discusses the definition of tumor boundaries during robot-assisted endogenic sinus tumor enucleation,the use of intraoperative cooling techniques,and the improvement of surgical safety.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.