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: Visual impairment is increasingly prevalent, underscoring the need for effective prevention strategies. This study investigated the association between cardiovascular health and visual impairment using three progressively developed metrics: Life’s Simple 7 (LS7), a cardiovascular health score developed by the American Heart Association based on 7 components, including physical activity, smoking status, body mass index (BMI), diet, blood glucose, blood pressure, and total cholesterol; Life’s Essential 8(LE8), which adds sleep health as an additional component; and Life’s Crucial 9 (LC9), which further incorporates mental health. We aimed to evaluate whether these expanded metrics provide additional explanatory value and to inform future public health strategies. Objective: To investigate the associations among LS7, LE8, and LC9 cardiovascular health scores and visual impairment in National Health and Nutrition Examination Survey 2013 to 2018, assess the added value of sleep and mental health components, and identify key contributing subcomponents using regression and machine learning methods. Methods: We analyzed data from 9891 participants in the 2013 to 2018 National Health and Nutrition Examination Survey. Multivariable logistic regression, restricted cubic spline modeling, and subgroup analyses were conducted to evaluate the association between cardiovascular health and visual impairment. Machine learning methods, including Random Forest and SHapley Additive exPlanations, a model interpretation approach used to assess feature importance, were applied. The Boruta algorithm, a feature selection method, was used to identify key subcomponents of cardiovascular health. Results: Participants with visual impairment were older, had lower poverty-to-income ratios, and exhibited lower cardiovascular health scores (LS7, LE8, and LC9). Higher cardiovascular health scores were negatively associated with visual impairment. Each one standard deviation increase in LS7, LE8, and LC9 was associated with approximately 8%, 2%, and 3% lower odds of visual impairment, respectively. LS7 showed the strongest negative association, whereas LE8 and LC9 emerged as the most important predictors in the machine learning models. Key subcomponents such as blood glucose, blood pressure, and BMI, as well as mental health status, were strongly associated with visual impairment. Conclusion: Higher cardiovascular health scores were negatively associated with visual impairment. LS7 demonstrated the strongest statistical association, whereas LE8 and LC9 were the most influential features in the machine learning models. Blood glucose, blood pressure, BMI, and mental health status were important correlates of visual impairment. From the perspective of the “prevention and treatment of diseases” in traditional Chinese medicine and the holistic concept, the aforementioned research findings confirm that severe visual impairment is indeed an external manifestation of overall health imbalance (such as organ dysfunction and Qi deficiency and blood stasis). The prevention strategy lies in comprehensively adjusting lifestyle, emotional factors, and metabolic indicators (corresponding to the key factors in the study) to restore the body’s internal balance and achieve prevention before disease arises.

Against the backdrop of a continuously rising incidence of breast cancer globally， breast reconstruction surgery represents one of the key measures to improve patients’ quality of life. Ethics of care emphasizes paying attention to patients’ actual needs in doctor-patient interactions and advocates creating a decision-making environment that facilitates the explicit expression of these needs. Focusing on the decision-making process of 16 breast cancer patients who underwent breast reconstruction surgery and stemming from the perspective of ethics of care， this paper explored the realization paths of autonomy for breast cancer patients when confronting medical decisions on breast reconstruction from three aspects， including the situatedness， relationality， and practicality of ethics of care. The study found that under the ethics of care， the organic interaction of contextualized practice， relational negotiation， and subjectivity cultivation jointly constructed a dynamically evolving medical decision-making ecosystem. This ecosystem， with situational response capabilities based on embodied cognition， relational adjustment mechanisms linked by ethical negotiation， and dual-track support networks aimed at subject empowerment， ultimately achieved the in-depth integration of technical practice and humanistic care.

Objective: To construct a prediction model for pelvic organ prolapse (POP) among primiparous women after vaginal delivery, so as to provide a basis for early screening and prevention of POP. Methods: Primiparous women after vaginal delivery at the First Hospital of Handan City from January 2022 to January 2025 were selected as study participants. Basic information including age and residence, as well as clinical characteristics including neonatal birth weight and forceps-assisted delivery, were collected. POP was diagnosed according to the Chinese Guidelines for the Diagnosis and Treatment of Pelvic Organ Prolapse (2020 Edition). LASSO regression and multivariable logistic regression model were used to analyze and screen independent predictors of POP among primiparous women after vaginal delivery, and a nomogram prediction model was constructed. The predictive performance of the nomogram prediction model was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, calibration curve, Hosmer-Lemeshow test, Brier score, and decision curve analysis. Results: A total of 200 primiparous women after vaginal delivery were included, of whom 169 (84.50%) were aged <35 years and 149 (74.50%) had a preconception body mass index (BMI) <24 kg/m2. POP occurred in 53 cases, with an incidence of 26.50%. Multivariable logistic regression analysis showed that age (≥35 years, OR=5.300, 95%CI: 1.824-15.399), preconception BMI (≥24 kg/m2, OR=4.371, 95%CI: 1.862-10.263), forceps-assisted delivery (OR=5.001, 95%CI: 1.847-13.536), prolonged duration of the second stage of labor (OR=3.659, 95%CI: 1.415-9.464), and neonatal birth weight (OR=4.695, 95%CI: 2.332-9.450) were independent predictors of POP among primiparous women after vaginal delivery. The constructed nomogram prediction model achieved an AUC of 0.902 (95%CI: 0.842-0.962), a sensitivity of 0.811, a specificity of 0.912, and an accuracy of 0.885, indicating good discrimination. The calibration curve, Hosmer-Lemeshow test (P>0.05), and Brier score (0.081) demonstrated good calibration. Decision curve analysis showed that when the risk threshold probability ranged from 0.12 to 0.70, the net benefit was relatively high. Conclusion The nomogram prediction model for POP constructed in this study exhibits good discrimination, calibration, and clinical utility, and has certain predictive value for POP risk among primiparous women after vaginal delivery.

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.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

Hypoxia and aberrant activation of epidermal growth factor receptor (EGFR) are considered important features of various malignancies. However, whether hypoxia can directly trigger EGFR activation and its clinical implications remain unclear. In this study, we demonstrated that in oral cancer, a typical hypoxic tumor, hypoxia can induce chronic but constitutive phosphorylation of wild-type EGFR in the absence of ligands. Oral cancer cell lines exhibit different EGFR phosphorylation responses to hypoxia. In hypoxic HN4 and HN6 cells, ubiquitination-mediated endocytosis, lysosomal sorting, and degradation lead to low levels of EGFR phosphorylation. However, in CAL-27 and HN30 cells, a novel HIF-1α-induced long noncoding RNA (lncRNA), EUDAL, can compete with the E3 ligase/adaptor complex c-Cbl/Grb2 for binding to EGFR, stabilizing phosphorylated EGFR (pEGFR) and resulting in sustained activation of EGFR and its downstream STAT3/BNIP3 signaling. STAT3/BNIP3-mediated autophagy leads to antitumor drug resistance. A high EUDAL/EGFR/STAT3/autophagy pathway activation predicts poor response to chemotherapy in oral cancer patients. Collectively, hypoxia can induce noncanonical ligand-independent EGFR phosphorylation. High EUDAL expression facilitates sustained EGFR phosphorylation in hypoxic tumor cells and leads to autophagy-related drug resistance.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/pathology* ; RNA, Long Noncoding/genetics* ; Drug Resistance, Neoplasm/genetics* ; Cell Line, Tumor ; Phosphorylation ; Signal Transduction ; STAT3 Transcription Factor/metabolism* ; Cell Hypoxia ; Autophagy ; Proto-Oncogene Proteins c-cbl/metabolism*