Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

ObjectiveTo investigate the relationship between periodontitis severity and brain functional indices-amplitude of low-frequency fluctuations （ALFF） and fractional ALFF （fALFF） in cognitively normal middle-aged and older adults， and to examine their associations with cognitive performance. Methods42 cognitively normal middle-aged and older participants were enrolled. Periodontal data—including the number of remaining teeth （NTP）， bleeding on probing positivity rate （BOP%）， probing depth （PD）， and clinical attachment loss （CAL） as well as resting-state functional magnetic resonance imaging data were collected. Participants were divided into a mild periodontitis group and a moderate-to-severe periodontitis group according to periodontitis severity. Group differences in ALFF and fALFF were compared， and correlation analyses were performed. ResultsCompared with the mild periodontitis group， the moderate-to-severe group showed decreased ALFF values in the right lingual gyrus， superior occipital gyrus， paracentral lobule， and in the left calcarine cortex as well as the precentral and postcentral gyri. Decreased fALFF values were observed in the right lingual gyrus， cuneus， and left calcarine cortex. Indicators related to periodontitis progression ［BOP%， PD=4-5 mm （%）， PD≥6 mm （%）， CAL=3-4 mm （%） and CAL≥5 mm （%）］ were negatively correlated with ALFF， fALFF and cognitive performance， whereas indicators reflecting better periodontal function ［PD=1-3 mm （%） and CAL=0-2 mm （%）］ were positively correlated with these measures. ConclusionIn cognitively normal middle-aged and older adults， periodontitis severity is associated with alterations in brain functional activity and cognitive performance.

Objective: To investigate the health literacy level and its influencing factors among the elderly in Shunyi District, Beijing Municipality, so as to provide the evidence for developing health literacy intervention measures and improving the elderly's health literacy level. Methods: From September to November 2024, permanent residents aged ≥60 years in Shunyi District were selected by a multi-stage random sampling method combined with probability proportionate to size sampling method. The Chinese Elderly Health Literacy Questionnaire was used to conduct face-to-face surveys on basic information, health status, and health literacy. The health literacy level of the elderly was analyzed. Multivariable logistic regression model and decision tree model were used to analyze the influencing factors for health literacy level of the elderly. Results: There were 285 males (47.50%) and 315 females (52.50%). The mean age was (68.91±7.38) years. The health literacy level of the elderly was 14.33%. The literacy levels of basic concepts, basic knowledge, and basic skills were 43.33%, 5.33%, and 50.83%, respectively. The literacy levels of scientific aging concept, intrinsic capacity and geriatric syndromes, healthy lifestyle, information acquisition and self-care, health service utilization and chronic disease management, and safety and first aid were 52.33%, 7.17%, 51.83%, 58.83%, 72.00%, and 4.33%, respectively. Multivariable logistic regression analysis showed that educational level (high school/technical secondary school/technical school and above, OR=2.376, 95%CI: 1.020-5.532), monthly household income per capita (1 000-<3 500 yuan, OR=2.973, 95%CI: 1.349-6.555), residence (urban, OR=3.836, 95%CI: 2.071-7.105), and health attention (relatively concerned, OR=4.164, 95%CI: 1.779-9.742) were influencing factors for health literacy level of the elderly. Decision tree model results showed that educational level, monthly household income per capita, residence, and health attention were influencing factors for health literacy level of the elderly, with residence being the main influencing factor. Elderly people living in urban areas, relatively concerned about health, and with high school/technical secondary school/technical school and above educational level had higher health literacy level (40.00%). Conclusions The health literacy level of the elderly in Shunyi District is mainly affected by educational level, monthly household income per capita, residence, and health attention. It is recommended to focus on rural elderly with lower educational level, monthly household income per capita, and health attention.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

The objective assessment of hearing loss is one of the critical components in forensic clini-cal research.Auditory brainstem response(ABR)is an important method for objectively assessing hearing levels.It is divided into various types based on different stimulus signals,each with its own characteris-tics and applications.Among them,narrow-band Chirp ABR,due to its frequency specificity,fulfills the basic requirements for objective assessment of forensic audiology,promising to be an important method of objective hearing assessment in forensic medicine.This article reviews the development history,charac-teristics and clinical applications of Chirp ABR,and envisions its application prospects in forensic audi-tory identification.

Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

BACKGROUND:Studies have shown that gut microbiota may affect the progression of rheumatoid arthritis.However,the causal relationship between the two is unknown.Mendelian randomization analysis of the two using published Genome Wide Association Study(GWAS)data can explore the causal relationship between gut microbiota and rheumatoid arthritis,helping to develop targeted microbial therapies and provide methods and strategies for the prevention and treatment of rheumatoid arthritis.OBJECTIVE:To explore the potential causal relationship between gut microbiota and rheumatoid arthritis using two-sample two-way Mendelian randomization method.METHODS:Gut microbiota GWAS data from the MiBio-Gen consortium and rheumatoid arthritis GWAS data from the IEU Open GWAS database(a large gene-phenotype association database developed at the MRC Integrative Epidemiology Unit(IEU)at the University of Bristol,UK)were used.Inverse variance weighting was used as the main analysis method,and MR-Egger regression method,weighted median method,weighted model and simple model method were used as supplements to study the causal relationship between gut microbiota and rheumatoid arthritis.Heterogeneity was assessed using Cochran's Q test,horizontal pleiotropy was assessed using MR-PRESSO and MR-Egger intercept tests,robustness of results was tested using leave-one method,and reverse Mendelian randomization analysis was used to assess the presence or absence of reverse causality.RESULTS AND CONCLUSION:(1)There was a causal relationship between five kinds of enteric bacteria and rheumatoid arthritis.Ruminococcus gauvreauii group(β=0.262,odds ratio[OR]=1.300,P=0.013)and Butyricimonas(β=0.001,OR=1.001,P=0.014)increased the risk of rheumatoid arthritis,while Anaerostipes(β=-0.225,OR=0.798,P=0.025),Lachnospiraceae-UCG010(β=-0.177,OR=0.838,P=0.026)and Oxalobacter(β=-0.171,OR=0.843,P=0.001)reduced the risk of rheumatoid arthritis.Sensitivity analyses showed no significant heterogeneity or horizontal pleiotropy(all P＞0.05),and leave-one-out testing confirmed the robustness of the results,while the addition of the remaining four methods other than the inverse variance weighting method further validated the reliability and stability of the results.(2)Reverse Mendelian randomization analysis did not find a causal association between rheumatoid arthritis and the five kinds of enteric bacteria identified by Mendelian randomization analysis.These findings indicate that Ruminococcus gauvreauii group and Butyricimonas may be the risk factors of rheumatoid arthritis,while Anaerostipes,Lachnospiraceae-UCG010 and Oxalobacter may be the protective factors of rheumatoid arthritis.Gut microbiota may play an important role in the pathogenesis of rheumatoid arthritis,and provide new biomarkers for the prevention and treatment of rheumatoid arthritis.In addition,for the field of biomedical research in China,we can learn from international experience and gradually establish and improve a multi-center large-scale genetic database,so as to deeply explore the relationship between gut microbiota and disease risk,and promote the development of precision medicine and personalized treatment in China.

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases