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.

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.

This study explored the effect of the Mycobacterium tuberculosis(Mtb)PE/PPE family protein PE_PGRS37 on the growth of Mycobacterium smegmatis(Ms)and macrophage autophagy during Mtb infection.The pe_pgrs37 gene was amplified from Mtb genome through PCR,and the recombinant vector pAIN-PE_PGRS37 was successfully constructed through homologous recombi-nation.pAIN-PE_PGRS37 and pAIN were integrated into Ms through electroshock to construct pAIN-PGRS37/Ms and pAIN/Ms re-combinant bacteria.Western blotting indicated that the PE_PGRS37 protein was correctly expressed in pAIN-PE_PGRS37/Ms.The re-combinant bacteria were inoculated in 7H9/7H10 medium,and their colony morphology and growth curves were observed.No signifi-cant difference in colony morphology was observed between pAIN-PE_PGRS37/Ms and pAIN/Ms.The growth rate significantly in-creased between 10 and 16 h,and a plateau was reached at 26 h.After infection of U937 cells with pAIN-PE_PGRS37/Ms and pAIN/Ms,macrophage autophagy flow was detected with western blotting and immunofluorescence.In the pAIN-PE_PGRS37/Ms-infected group,compared with the pAIN/Ms-infected group,macrophage LC3-II and p62 protein expression was significantly up-regulated(P<0.001)and inhibited autophagosome and lysosome fusion.The intracellular survival of the recombinant bacteria was detected through colony counting,and pAIN-PE_PGRS37/Ms showed significantly greater survival in macrophages at 12 h,24 h,and 48 h than pAIN/Ms(P<0.05).Our results suggested that PE_PGRS37 protein promotes Mycobacterium survival in macrophages by blocking macro-phage autophagy flow,thus inhibiting macrophage autophagy.

Objective:To evaluate strategies for screening and diagnosing Lynch syndrome associated endom-etrial carcinoma(LS-EC)in clinical practice and analyze clinicopathological characteristics of LS-EC.Methods:A total of 258 patients with endometrial carcinoma who underwent surgery in The Fourth Hospital of Hebei Medical University from January 2019 to January 2022 were included.All enrolled patients underwent postoperative immu-nohistochemical testing for mismatch repair(MMR)proteins.Based on the expression status of the four MMR proteins,the patients were divided into deficient mismatch repair(d-MMR)group(57 cases)and proficient mis-match repair(p-MMR)group(201 cases).Among them,23 patients in the d-MMR group underwent germline gene testing for Lynch syndrome(LS).According to germline gene testing results,these patients were further classified into LS-EC(n=8)and non-LS-EC(n=15)groups.Clinicopathological features of LS-EC patients were analyzed.Results:Among the 258 endometrial carcinoma patients,57cases(22.1%)exhibited d-MMR,with MLH1 and PMS2 co-deletion being the most common(61.4%,35/57).Among the23 d-MMR patients who under-went genetic testing,8 cases(34.8%)were identified as having LS-EC,including 5 cases(62.5%)of MLH1 gene mutation,1 case(12.5%)of MSH2 gene mutation,1 case(12.5%)of PMS2 gene mutation and 1 case(12.5%)of MSH6 gene mutation.Compared with the non-LS-EC group,the LS-EC patients showed significant familial aggregation and higher pathological grade(P<0.05).Conclusions:Immunohistochemical analysis of MMR proteins combined with family history represents an effective screening strategy for LS-EC,however defini-tive diagnosis requires germline genetic testing.Among LS-EC cases,MLH1 is the most frequently mutated gene.LS-EC patients are characterized by familial clustering and high pathological grade.Discrepancies between immu-nohistochistochemistry and genetic testing results present challenges in the definitive diagnosis of LS-EC.

Objective::Pulmonary hypertension secondary to left heart failure is associated with an abnormal response to exercise and poor prognosis. The objective of this study is to develop an algorithm by using data from cardiopulmonary exercise testing (CPET) to assess the severity of pulmonary hemodynamics and predict clinical worsening and mortality in patients with heart failure.Methods::From April 2017 to December 2018, a total of 102 patients with heart failure who underwent CPET and invasive right heart catheterization participated in this prospective study. All enrolled patients had their clinical characteristics, hemodynamic parameters, and CPET results. Based on the CPET data namely peak oxygen uptake, the minute ventilation/carbon dioxide production slope, resting end-tidal carbon dioxide, oxygen uptake/work rate flattening, exercise oscillatory ventilation, and oxygen uptake efficiency slope, a Heart Failure Cardiopulmonary Exercise (HFCE) score was developed. The total score was then calculated to categorize patients into 3 groups: low score (0-3) ( n = 31), intermediate score (4-7) ( n = 45), and high score (8-14) ( n = 26). Clinical events were defined as all-cause death and rehospitalization for heart failure, which were recorded and tracked for at least 12 months. Pearson’s correlation coefficients were calculated to assess the relationship between the HFCE score and hemodynamic parameters, 6-minute walk distance, and N-terminal-pro hormone brain natriuretic peptide. Cox proportional hazards regression analysis was used to identify independent predictors of clinical events. Survival curves for clinical events were generated using the Kaplan-Meier method and compared among the 3 groups with different HFCE scores with a log-rank test. Results::The high HFCE score group had a higher prevalence of New York Heart Association class Ⅲ-Ⅳ (high score vs. intermediate score vs. low score: 85% (22/26) vs. 56% (25/45) vs. 45% (14/31), P = 0.008), higher N-terminal-pro hormone brain natriuretic peptide levels (high score vs. intermediate score vs. low score: (3,039 ± 2,171) ng/L vs. (2,039 ± 2,353) ng/L vs. (1,438 ± 947) ng/L, P = 0.035), lower 6-minute walk distance (high score vs. intermediate score vs. low score: (312 ± 79) m vs. (362 ± 84) m vs. (363 ± 76) m, P = 0.042) compared to intermediate score or low score. The high HFCE score correlated well with high levels of pulmonary vascular resistance ( r = 0.539, P < 0.01), pulmonary artery wedge pressure ( r = 0.292, P < 0.01), and mean pulmonary artery pressure ( r = 0.474, P < 0.01), as well as low levels of cardiac output ( r = -0.357, P < 0.01). Moreover, 46 patients developed composed clinical events at 12 months. In the multivariate model, the HFCE score was an independent predictor of composed clinical events (hazard ratio = 1.142, 95% confidence interval: 1.041-1.253, P = 0.005). Kaplan-Meier analysis showed a significantly higher probability of composed clinical events in patients with a higher HFCE score ( P log-rank = 0.004). Conclusion::The HFCE score—obtained through CPET—provides valuable prognostic information by indicating the severity of hemodynamics in patients with pulmonary hypertension secondary to left heart failure. It can likely serve as a reliable predictor for clinical worsening and mortality.

Objective To observe the efficacy,safety,and compliance of lamotrigine combined with magnesium valproate in treating children with depressive episodes of bipolar disorder,and to explore the effects on thyroid hormone levels,brain-derived neurotrophic factor(BDNF),C-reactive protein(CRP),interleukin-1(IL-1),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α)and plasma concentration of valproate.Methods The children with bipolar disorder diagnosed from January 2023 to February 2025 were selected,and divided into the observation group and control group.The control group was treated with magnesium valproate tablets,and the observation group was added lamotrigine in addition to the treatment given to the control group.Both groups were treated continuously for 8 weeks.The clinical efficacy,the Hamilton Depression Scale-24(HAMD-24)score,Clinical Global Impression(CGI)assessment,thyroid hormone levels,BDNF,CRP,IL-1,IL-10 and TNF-α,daily average dose of magnesium valproate(D),blood concentration of valproate(C),C/D ratio,mean dosing interval(h),incidence of adverse reactions,and medication adherence and satisfaction scores in both groups was observed.Results A total of 100 children were included,50 in each group.After treatment,the total effective rate of the observation group was 98.00％which was significantly higher than that of the control group(84.00％)(P＜0.05).The serum free triiodothyronine(FT3),free thyroxine(FT4),BDNF and IL-10 in both groups increased compared to the previous(P＜0.05),while HAMD-24 score,CGI score,thyroid-stimulating hormone(TSH),CRP,IL-1 and TNF-α decreased(P＜0.05),and all indicators in the observation group were better than those in the control group(P＜0.05).Both groups had no serious or new adverse drug reactions,and the incidence of total adverse reactions,the difference in the incidence of total adverse reactions was not statistically significant(P＞0.05).There was no statistically significant difference in valproic acid blood concentrations between the two groups of children(P＞0.05).The medication compliance score and satisfaction score of the observation group were significantly higher than those of the control group(P＜0.05).Conclusion Combination of lamotrigine with magnesium valproate in children with depressive episodes of bipolar disorder improves treatment effective and clinical symptoms,promotes a rise in thyroid hormone and BDNF as well as improves inflammatory factors and increases medication adherence and satisfaction in children with a better safety profile.

Objective::Pulmonary hypertension secondary to left heart failure is associated with an abnormal response to exercise and poor prognosis. The objective of this study is to develop an algorithm by using data from cardiopulmonary exercise testing (CPET) to assess the severity of pulmonary hemodynamics and predict clinical worsening and mortality in patients with heart failure.Methods::From April 2017 to December 2018, a total of 102 patients with heart failure who underwent CPET and invasive right heart catheterization participated in this prospective study. All enrolled patients had their clinical characteristics, hemodynamic parameters, and CPET results. Based on the CPET data namely peak oxygen uptake, the minute ventilation/carbon dioxide production slope, resting end-tidal carbon dioxide, oxygen uptake/work rate flattening, exercise oscillatory ventilation, and oxygen uptake efficiency slope, a Heart Failure Cardiopulmonary Exercise (HFCE) score was developed. The total score was then calculated to categorize patients into 3 groups: low score (0-3) ( n = 31), intermediate score (4-7) ( n = 45), and high score (8-14) ( n = 26). Clinical events were defined as all-cause death and rehospitalization for heart failure, which were recorded and tracked for at least 12 months. Pearson’s correlation coefficients were calculated to assess the relationship between the HFCE score and hemodynamic parameters, 6-minute walk distance, and N-terminal-pro hormone brain natriuretic peptide. Cox proportional hazards regression analysis was used to identify independent predictors of clinical events. Survival curves for clinical events were generated using the Kaplan-Meier method and compared among the 3 groups with different HFCE scores with a log-rank test. Results::The high HFCE score group had a higher prevalence of New York Heart Association class Ⅲ-Ⅳ (high score vs. intermediate score vs. low score: 85% (22/26) vs. 56% (25/45) vs. 45% (14/31), P = 0.008), higher N-terminal-pro hormone brain natriuretic peptide levels (high score vs. intermediate score vs. low score: (3,039 ± 2,171) ng/L vs. (2,039 ± 2,353) ng/L vs. (1,438 ± 947) ng/L, P = 0.035), lower 6-minute walk distance (high score vs. intermediate score vs. low score: (312 ± 79) m vs. (362 ± 84) m vs. (363 ± 76) m, P = 0.042) compared to intermediate score or low score. The high HFCE score correlated well with high levels of pulmonary vascular resistance ( r = 0.539, P < 0.01), pulmonary artery wedge pressure ( r = 0.292, P < 0.01), and mean pulmonary artery pressure ( r = 0.474, P < 0.01), as well as low levels of cardiac output ( r = -0.357, P < 0.01). Moreover, 46 patients developed composed clinical events at 12 months. In the multivariate model, the HFCE score was an independent predictor of composed clinical events (hazard ratio = 1.142, 95% confidence interval: 1.041-1.253, P = 0.005). Kaplan-Meier analysis showed a significantly higher probability of composed clinical events in patients with a higher HFCE score ( P log-rank = 0.004). Conclusion::The HFCE score—obtained through CPET—provides valuable prognostic information by indicating the severity of hemodynamics in patients with pulmonary hypertension secondary to left heart failure. It can likely serve as a reliable predictor for clinical worsening and mortality.