OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke， and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025， wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment， patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data， metabolic phenotype， the levels of platelet function indicators and inflammatory cytokines. Variables with P ＜0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included； among them， 162 cases were normal metabolic phenotype， 218 were intermediate metabolic phenotype， and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment， platelet aggregation rate， the levels of P-selectin and platelet activated complex-1 （PAC-1）， high-sensitivity C-reactive Protein （hs-CRP）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in the normal metabolic phenotype group， intermediate metabolic phenotype group， and poor metabolic phenotype group （except for platelet aggregation rate， and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group） were significantly lower than those before treatment in the same group. Moreover， the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time， and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time （ P ＜0.05）. Univariate and multivariate Logistic regression analyses showed that combined with hypertension， combined with diabetes mellitus， and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke （ P ＜0.05）. Multiple linear regression analysis showed that serum levels of hs-CRP， IL-1β， IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype （ P ＜0.05）， with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype； CYP2C19 gene polymorphism， and in combination with hypertension and diabetes， can be used as independent predictors of poor prognosis.

Despite of the widespread use of hydrogen and methane breath test, the variability in testing protocols, gas measurement techniques, and interpretation criteria continues to challenge the reproducibility and comparability across centers, especially in the Asia-Pacific region. The Asian Neurogastroenterology and Motility Association hence presents the first Asian monograph guiding application and interpretation of breath test. The monograph was formulated according to the framework of indications, preparatory process, performance, and interpretation of results, as well as future direction for research.

Background/Aims: Belching can occur either independently or concurrently with reflux symptoms. This study aims to explore the relationship between belching and reflux and explore the underlying mechanisms involved. Methods: Firstly, patients with isolated belching symptoms or concurrent belching and reflux symptoms were retrospectively enrolled. High-resolution esophageal impedance manometry (HRIM) and 24-hour pH impedance monitoring were used to assess belching types and temporal relationship between belching and reflux. Secondly, subjects with belching disorder were prospectively recruited. Postprandial HRIM monitoring was used to clarify the relationship and underlying mechanisms between belching and reflux. Results: In the initial phase, 139 subjects were enrolled. Regardless of patients' symptom spectrum (with or without gastroesophageal reflux symptoms), the proportion of preceding-reflux belching was significantly higher in those with objective evidence of gastroesophageal reflux disease, compared to those without (both P < 0.05), which indicated that belching could trigger reflux events and led to more severe reflux burden. To clarify the potential mechanisms involved, 44 belching subjects were prospectively enrolled in the second phase of this study. HRIM analysis demonstrated that maximum intragastric pressure, gastric–lower esophageal sphincter pressure gradient and gastric–esophageal pressure gradient were significantly higher in preceding-reflux belching than those in independent belching. Conclusions This study demonstrated that belching might trigger reflux by increasing intragastric pressure, elevating the gastric-sphincter pressure gradient, which enables gastric contents to pass through the esophagogastric junction.These findings have crucial clinical significance, suggesting that reducing the occurrence of belching might be a potential treatment for refractory reflux.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Based on the theories of "pathogenesis caused by constraint emotions" and "visceral orifices"， it is believed that the pathogenesis of tinnitus caused by constraint syndrome follows the evolution pattern of "qi constraint （liver qi constraint） → fire disturbance （liver constraint transforming into fire） → deficiency impairment （liver constraint with spleen deficiency） → blood stasis （liver constraint leading to blood stasis）". The treatment is guided by the principle of integrated internal and external therapy with harmonization of both body and mind. Internally， the treatment focuses on rectifying zang-fu imbalances， primarily using the Xiaoyao Powder （逍遥散）， with modifications based on syndrome differentiation. External therapies aim to unblock the meridians and orifices， commonly using auricular acupressure and Chinese herbal hot compresses. Additionally， traditional Chinese five-tone music therapy is applied to regulate emotional and mental disturbances. By integrating these three approaches， a comprehensive treatment strategy is formed that harmonizes both body and mind for managing tinnitus associated with constraint syndrome.

This study explored whether Astragalus polysaccharide(APS)can regulate the VEGF/VEGFR signaling pathway to affect the proliferative activity of rat intestinal mucosal microvascu-lar endothelial cells(RIMMVECs).RIMMVECs were isolated from newborn rats,then purified and treated with APS at concentrations of 0.1,1.0,10.0,100.0,1 000.0,and 10 000.0 mg/L.MTT was used to determine the effect of APS on RIMMVECs proliferation and screen for the optimal concentration of APS.Subsequently,flow cytometry was used to detect the changes in cell cycle to evaluate the stage of action of APS on the cell cycle in RIMMVECs.Then,the ELISA was used to detect the changes of VEGFA in cell supernatant to evaluate the potential of cell proliferation and angiogenesis.The changes in fluorescence intensity of Fluo-8AM was observed using fluorescence microscopy to evaluate intracellular Ca2+levels.Finally,Western blot was used to detect the ex-pression of PERK in RIMMVECs to analyze the possible mechanism of APS.The results showed that 100 mg/L APS significantly enhanced the proliferative activity of RIMMVECs,increased the content of VEGFA in the cell supernatant,the intracellular Ca2+levels,and the expression of PERK protein,indicating that APS promotes the proliferation of RIMMVECs,which may be a-chieved by promoting the expression of VEGFA and activating the ERK pathway.

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

Objective To observe the effect of a heavy load exercise on the ultrastructure,function and fission of skeletal muscle mitochondria in rats,and to analyze the changes of the phosphorylation expression of mitochondrial fission protein and upstream kinase at different times postexercise,and to explore the effect of acute heavy load exercise on mitochondrial fission in skeletal muscle of rats and its possible mechanism.Methods Forty-eight adult male Sprague-Dawley rats were randomly divided in-to a quiet control group(C,n=8)and an exercise group(E,n=40).Rats in the E group exercised on a treadmill down a 16° decline at 16 m/min for 90 min and were further divided into 0 h,12 h,24 h,48 h,and 72 h postexercise subgroups.Soleus muscle was isolated and mitochondria were ex-tracted at the corresponding time points after exercise.The ultrastructure of mitochondria in the soleus muscle was observed using transmission electron microscopy,and mitochondrial quantity and morphomet-ric analysis were conducted.Moreover,the colocalization and quantity of dynamin-related protein 1(Drp1)and cytochrome C oxidease subunit Ⅳ(COXⅣ)in the soleus muscle were detected using im-munofluorescence double-labeling techniques.Meanwhile,protein levels of soleus musclep-Drp1Ser616,p-Drp1Ser637,p-extracellular regulatory protein kinaseThr202/Tyr204(p-ERKThr202/Tyr204),p-protein kinaseAThr197(p-PKAThr197),and mitochondrial NADH of ubiquinone oxidoreductase subunit B8(NDUFB8)and ubiqui-nol-cytochrome C reductase core protein 2(UQCRC2)were determined by using Western blotting.An-other twenty-four rats were randomly divided into a DMSO group(CD),a U0126 group(CU),an Ex-ercise+DMSO group(ED),and an Exercise+U0126 group(EU).Six mice in each group were giv-en a single intra-bitoneal injection of DMSO or ERK inhibitor U0126 20 min before acute downhill running.Then,their phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 in soleus muscle were de-tected by Western blotting.Results(1)From 0 h to 48 h after exercise,the soleus muscle mitochon-dria showed swelling,rounding,and uneven distribution of mitochondria,among which the degree of mitochondrial damage was the most serious at 12 h and 24 h after exercise.Moreover,the protein ex-pression of NDUFB8 and UQCRC2 in the mitochondria fractions from soleus muscle was significantly lower at 12 h post-exercise(P<0.05).(2)The co-localization of Drp1 and COXⅣ in the skeletal muscle increased significantly at 12 h to 24 h after a heavy load exercise compared with group C and group E0(P<0.01).Moreover,the mitochondrial area,circumference,aspect ratio and Ferret diameter in the skeletal muscle were significantly lower at 12 h to 24 h postexercise(P<0.05).Meanwhile,the number of mitochondria was significantly higher at 24 h after exercise(P<0.01).(3)The phosphoryla-tion of ERKThr202/Tyr204,PKAThr197 and Drp1Ser616 was significantly higher at 24 h after exercise(P<0.01),while that of Drp1Ser637 was significantly lower at 48 h and 72 h post-exercise(P<0.01).However,the phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 were significantly down-regulated by U0126 treatment before exercise.Conclusion A session of heavy load exercise caused mitochondrial structure and function damage and induced mitochondrial fission in the skeletal muscle,and then to maintain the homeostasis of skeletal muscle cells by cleaving damaged mitochondria.The mechanism of promot-ing skeletal muscle repair may be related to the positive and negative regulation of Drp1 activity by the phosphorylation of Drp1Ser616 and Drp1Ser637,respectively.Among them,the activation of ERKThr202/Tyr204 mediates the phosphorylation activation of Drp1Ser616,but PKAThr197 is not an upstream kinase that medi-ates the inactivation of Drp1Ser637 phosphorylation.

The interaction between epithelial cells and macrophages plays a crucial role in the progression of lung diseases,including immune de-fense,inflammation regulation,tissue repair,and regeneration.However,an imbalance in this inter-action can contribute to the development of vari-ous lung diseases.In idiopathic pulmonary fibrosis,chronic obstructive pulmonary disease,and lung cancer,macrophages can promote disease progres-sion by secreting cytokines that act on epithelial cells.Simultaneously,activated epithelial cells re-lease cytokines to recruit and activate more macro-phages in a positive feedback loop.Thus,compre-hensive studies of the interactions between epithe-lial cells and macrophages in various lung diseases have the potential to identify new therapeutic tar-gets and develop innovative strategies for disease management.This review aims to summarize the current knowledge regarding the interaction be-tween epithelial cells and macrophages in idiopath-ic pulmonary fibrosis,chronic obstructive pulmo-nary disease,and lung cancer,with the goal of in-spiring new research directions for the treatment of lung diseases.

Objective:To systematically search and summarize high-quality evidence-based evidence on the prevention and management of refeeding syndrome in patients with anorexia nervosa, and to provide a basis for preventive management of patients at high risk.Methods:A computerized search was conducted for evidence on the prevention and management of refeeding syndrome in patients with anorexia nervosa in relevant domestic and international databases and professional team websites, including clinical decision-making, guidelines, expert consensus, evidence summaries and systematic evaluations, and randomized controls. The search timeframe was from database construction to August 2024. Two researchers trained in systematic evidence-based knowledge independently performed literature screening, quality assessment, and extraction and summarization of evidence according to inclusion and exclusion criteria.Results:A total of 15 publications were included, which contained 4 guidelines, 3 expert consensus, 3 clinical decision-making, 3 systematic evaluations, and 2 randomized control trials. Thirty-one pieces of evidence for the prevention and management of refeeding syndrome were summarized in seven areas: treatment team, risk factors, risk assessment, preventive measures, clinical diagnosis, management measures, and patient safety.Conclusions:The best evidence summarized in this study for the prevention and management of refeeding syndrome in anorexia nervosa provides an evidence-based basis for practitioners to implement refeeding syndrome prevention and management measures.