ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

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.

Background: This study was performed to characterize the incidence, costs, and risk factors associated with renal and cardiovascular adverse outcomes following primary percutaneous coronary intervention (pPCI) in patients with ST-elevation myocardial infarction (STEMI). Methods: Patients with STEMI who underwent pPCI using iso-osmolar contrast were enrolled at 39 centers. The incidence of acute kidney injury (AKI) and major adverse renal and cardiovascular events (MARCE) was analyzed, as well as inpatient costs. Logistic regression analysis was performed to identify risk factors. Results: Among 2,293 patients, the incidence of AKI and MARCE within 72 hours post-pPCI was 4.14% (n = 95) and 4.40% (n = 101), respectively. AKI and/or MARCE were associated with systolic blood pressure (AKI: odds ratio [OR], 1.009; 95% confidence interval [CI], 1.000–1.018), hypertension (AKI: OR, 1.815; 95% CI, 1.133–2.906; MARCE: OR, 1.760;95% CI, 1.118–2.769), anterior wall infarction (AKI: OR, 1.895; 95% CI, 1.196–3.004; MARCE:OR, 1.939; 95% CI, 1.240–3.032), Killip class (AKI: OR, 1.465; 95% CI, 1.117–1.922; MARCE:OR, 1.467; 95% CI, 1.131–1.903), and serum creatinine (SCr; MARCE: OR, 1.006; 95% CI, 1.000–1.012). Hospitalization costs for patients with STEMI who developed AKI or MARCE were significantly higher than for those without AKI (9,595 ± 5,795 vs. 8,279 ± 3,872 USD, P = 0.003) or without MARCE (9,890 ± 5,616 vs. 8,255 ± 3,859 USD, P < 0.001). Conclusions In patients with STEMI undergoing pPCI with iso-osmolar contrast, the incidence of AKI and MARCE was associated with higher hospitalization costs. Systolic blood pressure, hypertension, anterior wall infarction, Killip class, and SCr were identified as risk factors for these outcomes.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

ObjectiveThis study aimed to provide a scientific basis for the safety management of drinking water by assessing the contamination levels of 21 per- and polyfluoroalkyl substances (PFASs) in water samples collected from the Yangtze River Delta region. MethodsSolid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to determine 21 PFASs in 6 source water samples, 20 treated water samples, and 60 tap water samples collected from 5 administrative districts in the Yangtze River Delta region across four seasons in 2023. The Kruskal-Wallis H test was used to compare differences in PFAS concentrations among the three types of water samples, followed by post hoc pairwise comparisons with Bonferroni correction. Removal efficiencies of target compounds were also calculated. ResultsAmong the 86 samples, 14 PFASs were detected, with 7 compounds detected in 100% of samples. The total concentrations of PFASs in source water, treated water, and tap water ranged from 63.85 to 190.54 ng·L^-¹, 55.75 to 774.36 ng·L^-¹, and 40.72 to 689.80 ng·L^-¹, respectively. The compounds with the highest median concentrations were perfluorobutanoic acid (PFBA) (40.19, 15.20, and 14.05 ng·L^-¹), perfluorohexanoic acid (PFHxA) (29.69, 32.62, and 34.24 ng·L^-¹), perfluorooctanoic acid (PFOA) (17.65, 39.45, and 36.83 ng·L^-¹), and potassium perfluorobutanesulfonic acid (PFBS) (16.99, 24.38, and 23.89 ng·L^-¹). Notably, concentrations of PFOA (7.71‒71.63 ng·L^-¹) and PFOS (-¹) in tap water were below the regulatory limits specified in GB 5749‒2022 Standards for Drinking Water Quality (PFOA: 0.000 08 mg·L^-1, PFOS: 0.000 04 mg·L^-1). Significant seasonal variations in PFAS concentrations were observed, with total PFAS levels in March being higher than those in September and November (adjusted P<0.001, and P=0.006), and levels in May being higher than those in September (adjusted P=0.037). The removal efficiencies of PFASs in the water treatment plants ranged from -14% to 34%. ConclusionPFAS contamination is widespread in source water, treated water, and tap water in the Yangtze River Delta region, and concentrations of PFOA and PFOS in all tested water samples comply with the Chinese national standards for drinking water quality (GB 5749‒2022). The use of PFASs should be continuously regulated to ensure water safety.

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, which not only affects the digestive tract, but also involves extraintestinal organs and tissues such as joints and eyes, and ultimately endangers human health and affects the quality of life of patients. With the development of information technology, there is an increasing application of digital therapeutics in the management of IBD. This article aims to comprehensively analyze the characteristics, use, and challenges of digital therapeutics in the management of IBD, and explore its potential to improve treatment adherence, disease surveillance, and improve patients' quality of life.

Objective:To predict the occurrence of chronic radiation enteritis (CRE) in cervical cancer patients by developing a prediction model based on the combination of radiomic features derived from magnetic resonance imaging (MRI) scans and clinical parameters, in order to provide a reference for clinicians to determine the prognosis of these patients and offer them individualized diagnosis and treatment.Methods:A retrospective analysis was conducted on 111 cervical cancer patients who received radical radiotherapy at the First Affiliated Hospital of Anhui Medical University. Radiological features were extracted from the T1-weighted MRI images of local lesions of cervical cancer obtained before the radiotherapy. Features were selected using the least absolute shrinkage and selection operator (LASSO) to obtain the radiomics score. The radiomics scores and clinical parameters were assessed using univariate and multivariate logistic regression analyses, followed by the establishment of nomograms. The ability of radiomics to achieve CRE prediction was assessed using the area under the curve (AUC) and the calibration and decision curves.Results:Multivariate logistic regression analysis result revealed that the independent risk factors for identifying CRE in patients included radiomics score ( HR: 17.457, 95% CI: 5.540-55.009, P<0.001), tumor volume ( HR: 3.617, 95% CI: 1.293-10.115, P=0.014), and pelvic lymph node metastasis ( HR: 3.559, 95% CI: 1.013-12.501, P=0.048). The model combining radiomics and clinical data demonstrated high performance, with its AUCs of the training and validation groups (0.888 and 0.870, respectively) higher than those of the radiomics model (0.842 and 0.804, respectively) and the clinical data model (0.721 and 0.704, respectively). The analyses of calibration and decision curves confirmed the application value of clinical radiomic nomograms. Conclusions:The model combining radiomics and clinical data allows for accurate CRE prediction. Therefore, radiomic features have the potential to serve as a promising imaging biomarker for CRE.

Aim To investigate the effects of astragalo-side Ⅳ(AS-Ⅳ)on proliferation,apoptosis and the discoid domain receptor 1/phosphatidylinositol 3-ki-nase/protein kinase B(DDR1/PI3K/Akt)signaling pathway of HL-60 cells in acute myeloid leukemia.Methods The experiment was divided into the control group(Control),AS-Ⅳ intervention group,control+DDR1 gene interference group(Control+sh-DDR1),AS-Ⅳ+DDR1 gene overexpression group(AS-Ⅳ+OVE-DDR1)and AS-Ⅳ+OVE-DDR1+PI3K inhibi-tor group(AS-Ⅳ+OVE-DDR1+LY294002).After 72 h of AS-Ⅳ intervention,the proliferation inhibition rate was measured by CCK-8;apoptosis was detected by flow cytometry and Hoechst33258 staining;and the expression levels of DDR1/PI3K/Akt signaling path-way proteins,proliferation and apoptosis-related pro-teins were detected by Western blot.Results Com-pared with the Control group,the AS-Ⅳ group showed significantly lower proliferation rate and higher apopto-sis rate(P＜0.01),cells showed apopt otic morpholog-ical changes such as nuclear sequestration and nuclear fragmentation,and the expression of DDR1,p-PI3K,p-Akt,CyclinD1 and Bcl-2 proteins were significantly lower and caspase-3 protein expression was significant-ly higher(P＜0.01).Compared with the AS-Ⅳ group,cell proliferation rate was significantly higher and apoptosis rate was significantly lower in the AS-Ⅳ+OVE-DDR1 group(P＜0.01),and DDR1,p-PI3K,p-Akt,CyclinD1,and caspase-3 protein expression were significantly higher and Bcl-2 protein expression was significantly lower in the AS-Ⅳ+OVE-DDR1 group(P＜0.01).Compared with the AS-Ⅳ+OVE-DDR1 group,the cell proliferation rate was significantly lower and apoptosis rate was significantly higher in the AS-Ⅳ+OVE-DDR1+LY294002 group(P＜0.01),and DDR1,p-PI3K,p-Akt,CyclinD1,and caspase-3 protein expression were significantly lower and Bcl-2 protein expression was significantly higher in the AS-Ⅳ+OVE-DDR1+LY294002 group(P＜0.01).Conclu-sion AS-Ⅳ can inhibit proliferation and promote ap-optosis in acute myeloid leukemia HL-60 cells by a mechanism related to the inhibition of DDR1/PI3K/Akt signaling pathway.

BACKGROUND:H uman pluripotent stem cell-derived cardiomyocytes offer an ideal cellular resource for studying heart diseases,conducting drug screening,developing in vitro heart models,and exploring potential cell therapies.However,human pluripotent stem cell-derived cardiomyocytes are characterized by immaturity with limited specific gene expression,low Ca2+processing levels,and underdeveloped structural,metabolic,and electrophysiological features.These limitations significantly impede the application of human pluripotent stem cell-derived cardiomyocytes.OBJECTIVE:To review the academic progress and clinical application of promoting the maturation of human pluripotent stem cell-derived cardiomyocytes by in vitro synthetic microenvironment.METHODS:CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases were searched,with"human pluripotent stem cells,human myocardial cells,hPSC-CMs,mature,OA,human pluripotent stem cell-derived cardiomyocytes,hPSC-CMs"as English search terms and"human pluripotent stem cells,cardiomyocytes,mature,OA,hPSC-CMs"as Chinese search terms.All relevant literature published from January 2002 to July 2024 was retrieved and 82 articles were included in the review.RESULTS AND CONCLUSION:(1)In recent years,in vitro synthetic microenvironments have attracted extensive attention due to their excellent intrinsic properties such as stiffness,plasticity,nanoscale morphology,and chemical functionality.(2)Human pluripotent stem cell-derived cardiomyocytes can be used as an effective platform for the treatment of cardiovascular diseases.(3)Mechanical stimulation,electrical stimulation,addition of biochemical molecules,and three-dimensional culture methods are effective methods to promote the maturation of human pluripotent stem cell-derived cardiomyocytes,which can further promote the clinical application of human pluripotent stem cell-derived cardiomyocytes.

Objective To predict the poorly differentiated subtype of stage T1 invasive lung adenocarcinoma based on the morphological and quantitative characteristics of preoperative CT images.Methods The CT images,clinical information and pathological report of 333 cases with stage T1 lung adenocarcinoma in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and the Second Affiliated Hospital of Naval Medical University were retrospectively analyzed.All data were divided into histological subtypes according to the WHO Classification of Chest Tumors(5th Edition).CT signs include the maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,lobular sign,vacuole sign,air bronchial sign,halo sign,bronchial truncation sign,vascular cluster sign,pleural depression sign.Clinical factors included gender,age,smoking history,tumor markers,and spread through air spaces.Independent predictors of poorly differentiated subtypes of lung adenocarcinoma were obtained via univariate and multivariate logistic regression analysis,and the clinical model,CT model and combined model were constructed based on the analysis results.Results In univariate logistic regression analysis,gender,smoking history,tumor markers,spread through air spaces,maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,vacuole sign and vascular cluster sign were significantly related to poorly differentiated subtypes.Multivariate logistic regression analysis showed that gender,tumor markers,vacuole sign,minimum diameter,and nodule type were independent influencing factors of poorly differentiated subtypes of lung adenocarcinoma.Clinical model,CT model and combined model were constructed based on the analysis results.Area under the curve(AUC)of the clinical model,CT model and combined model were 0.772[95％confidence interval(CI)0.712-0.831],0.776(95％CI 0.714-0.837)and 0.825(95％CI 0.776-0.874)for the poorly differentiated subtypes,respectively.The combined model had a higher AUC,with the better prediction.There was significant difference in predicting lung adenocarcinoma poorly differentiated subtypes between the clinical model and combined model(P=0.019).Conclusion Logistic regression model based on CT signs has good diagnostic value in predicting poorly differentiated lung adenocarcinoma in stage Ⅰ.