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.

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

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.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P＜0.05,P＜0.01),and the high-dose EPL group reduced the serum RF in mice(P＜0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P＞0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P＜0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P＜0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P＜0.01).EPL significantly increased the pro-tein expression of Bcl-2(P＜0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P＜0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.

Objective:To evaluate the efficacy of shockwave therapy,acupuncture,hyperthermia,biofeedback therapy,elec-trical nerve stimulation,magnetotherapy and ultrasound therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS),and to provide evidence-based support for clinical decision-making.Methods:Two researchers independently searched PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and Chinese Biomedical Literature databases for randomized controlled trials(RCTs)on the effects of different interventions on CP/CPPS from the establishment of the databases to August 2024.We evaluated the quality of the included literature and extracted the relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions,followed by network meta-analysis using Revman 5.3,R 4.33 and Stata17 software.Results:A total of 25 RCTs involving 1 794 cases were included.The results of network meta-analysis showed that electrical nerve stimulation,shockwave therapy,biofeedback therapy,magnetotherapy,ultrasound therapy and acupuncture were significantly superior to conventional medication and placebo in the total NIH-CPSI scores(P＜0.05),and so were electrical nerve stimulation and shock-wave therapy to acupuncture and hyperthermia(P＜0.05),magnetic therapy to hyperthermia,and ultrasound therapy to placebo(P＜0.05).Shockwave therapy,biofeedback therapy,electrical nerve stimulation,magnetotherapy and ultrasound therapy achieved re-markably better clinical efficacy than conventional medication and placebo in the treatment of CP/CPPS,and so did shockwave therapy than electrical nerve stimulation,hyperthermia,ultrasonic therapy,magnetotherapy and acupuncture.Conclusion:For the treat-ment of CP/CPPS,electrical nerve stimulation is advantageous over the other interventions in improving total NIH-CPSI scores,and shockwave therapy is advantageous in relieving pain symptoms and clinical efficacy.This conclusion,however,needs to be further veri-fied by more high-quality clinical studies.

Objective:To investigate the expression characteristics of the SLFN11 gene in pancreatic cancer and its relationship with cis-diamminedichloroplatinum(DDP)resistance.Methods:This study analyzed multiple publicly available datasets, including GSE207611, GSE186205, GSE73978, GSE217845, and GSE238163 from the gene expression omnibus(GEO)datasets.These datasets comprise gene expression data and single-cell sequencing data from pancreatic cancer cell lines and patients, which were utilized to examine the expression characteristics of the SLFN11 gene and its association with cisplatin resistance.Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) value along with the confidence interval ( CI) were calculated.Additionally, Kaplan-Meier survival analysis and single-cell RNA sequencing(scRNA-seq)data analysis were conducted. Results:The differential expression of the SLFN11 gene between tumor and adjacent normal tissues was statistically significant( P<0.05). The AUC value for SLFN11 in diagnosing pancreatic cancer was 0.761.SLFN11, along with its associated genes PTN and SLC15A3, collectively influenced the survival of pancreatic cancer patients.Results from single-cell sequencing demonstrated high expression of SLFN11 in mesenchymal stem cells. Conclusions:The SLFN11 gene demonstrates significant diagnostic and prognostic value in pancreatic cancer and may play a role in the mechanism of cisplatin resistance.

The time-sensitive medical treatment advantages of unmanned aerial vehicles(UAVs)in casualty evacuation were described,along with their typical application scenarios and the principles of casualty evacuation.The development status of UAV-based casualty evacuation,both domestically and internationally,was reviewed.Key life-support technologies,such as intelligent injury recognition,fully automated cardiopulmonary resuscitation(CPR)and auto cruise-based mecha-nical ventilation,were examined as important research directions of casualty evacuation UAVs.Finally,future development trends in UAV casualty evacuation and transport system were envisioned from four dimensions of autonomous flight technology,life support systems,information interaction and policy regulations.

Sustainability is a critical issue in China's medical and health assistance and cooperation with Africa.As China enters a new phase in this field,achieving sustainability presents both opportunities and challenges.Summarizing past successes and identifying barriers are of great practical significance for future development.This study examines the current state of China's medical and health assistance and cooperation with Uganda and finds that China has actively sought to integrate into local communities by collaborating with Ugandan medical institutions.However,several factors continue to constrain the sustainability of these efforts,including Uganda's fragmented public-private healthcare system heavily reliant on external aid,the personnel structure of Chinese medical teams,and linguistic and cultural barriers between China and Uganda.Based on official policy documents from both countries and field research findings,this study recommends supporting and assisting Uganda in establishing an independent healthcare system,with a particular focus on maternal and child health,youth health,and chronic disease management.Furthermore,strengthening cultural exchanges can contribute to the sustainable development of China-Uganda and broader China-Africa medical and health assistance and cooperation.

Objective:To investigate the preferences and influencing factors of Traditional Chinese Medicine(TCM)health management services among community healthcare workers,providing a reference for promoting and spreading TCM health management services in communities.Methods:Based on a discrete choice experiment,a questionnaire survey was conducted among 596 community healthcare workers across 9 administrative districts in Beijing.A mixed logit model was used to analyze their preferences.Results:Changes in post-tax monthly income,expected efficacy,single-service duration,technical difficulty,patient compliance,and insurance coverage significantly influenced community doctors'service preferences.Changes in post-tax monthly income had the highest relative importance(35.11%),followed by insurance coverage(34.87%).Preferences varied among healthcare workers with different professional titles,backgrounds,weekly working hours,and whether the service was included in performance evaluations.Conclusion:Both economic and non-economic factors influence community healthcare workers'service preferences to varying degrees.Optimizing the combination of TCM health management service attributes can enhance community healthcare workers'willingness to provide such services.It is recommended to use a combination of economic and non-economic incentive measures and develop differentiated strategies for healthcare workers with different characteristics to meet their service preferences and promote the development of TCM health management services in communities.