Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

OBJECTIVE: To observe the effects of moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) on the circular RNA of exon 2-5 of the Pan3 gene (circPAN3), forkhead box O3 (FOXO3), and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in rats with chronic heart failure (CHF), and explore the potential mechanisms of moxibustion in alleviating myocardial fibrosis. METHODS: Ten rats of 60 male SPF-grade SD rats were randomly assigned into a normal group. The remaining rats underwent left anterior descending coronary artery (LAD) ligation to establish the CHF model. Forty successfully modeled rats were randomly divided into a model group, a moxibustion group, a rapamycin (RAPA) group, and a moxibustion+RAPA group, with 10 rats in each group. The moxibustion group received mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15), 30 min per session. The RAPA group received intraperitoneal injection of the autophagy activator RAPA (1 mg/kg). The moxibustion+RAPA group first received RAPA injection, followed by mild moxibustion at bilateral "Feishu" (BL13) and "Xinshu" (BL15). All interventions were administered once daily for 4 consecutive weeks. After the intervention, cardiac ultrasound was used to measure ejection fraction (EF) and left ventricular fractional shortening (FS). Serum placental growth factor (PLGF) level was determined by ELISA. Myocardial tissue morphology and collagen volume were assessed using hematoxylin-eosin (HE) staining and Masson's trichrome staining. The expression levels of circPAN3, FOXO3, and BNIP3 mRNA in myocardial tissue were detected by real-time PCR, while FOXO3 and BNIP3 protein expression levels were analyzed by Western blot. RESULTS: Compared with the normal group, the model group exhibited myocardial cell disorder, severe fibrosis, and increased collagen volume (P<0.01), along with significantly decreased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and the serum PLGF level, as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue were increased (P<0.01). Compared with the model group, the moxibustion group showed reduced myocardial fibrosis, decreased collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). Compared with the model group, the RAPA group showed further deterioration in these parameters (P<0.01). Compared with the RAPA group, the moxibustion+RAPA group exhibited alleviation of myocardial fibrosis, reduced collagen volume (P<0.01), increased EF, FS, and circPAN3 mRNA expression in myocardial tissue (P<0.01), and decreased serum PLGF level as well as FOXO3 and BNIP3 mRNA and protein expression in myocardial tissue (P<0.01). CONCLUSION Moxibustion could alleviate myocardial fibrosis in CHF rats, possibly through upregulation of myocardial circPAN3 expression, downregulation of FOXO3 and BNIP3 expression, and inhibition of excessive myocardial autophagy.
Animals ; Moxibustion ; Heart Failure/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Myocardium/pathology* ; RNA, Circular/metabolism* ; Membrane Proteins/metabolism* ; Forkhead Box Protein O3/metabolism* ; Acupuncture Points ; Humans ; Fibrosis/genetics* ; Chronic Disease/therapy* ; Mitochondrial Proteins

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective To analyze the characteristics of real-world adverse drug events(ADEs)of trabectedin based on the FDA Adverse Event Reporting System(FAERS)database in order to provide references for clinical drug safety management.Methods A total of 1 349 trabectedin-related reports were extracted from the FAERS database from Q1 2007 to Q4 2024.Using the MedDRA coding classification system for system organ class(SOC)and preferred term(PT),signal detection was performed through 4 proportional imbalance methods,including reporting odds ratio(ROR)and proportional reporting ratio(PRR).Subgroup analyses by gender,age,and temporal trends were also conducted.Results Hematological and lymphatic system disorders and hepatobiliary system disorders were the primary SOCs involved.High-frequency PTs included neutropenia(123 cases)and anemia(117 cases).Eight potential ADEs that have not been listed in the drug product instruction were identified.The median onset time of ADEs was 21 d,showing an early failure pattern,with differences observed by gender(females more prone to hematological toxicity)and age(elderly more susceptible to febrile neutropenia).Conclusion Trabectedin requires close attention to hematological toxicity,hepatotoxicity,and newly identified multi-system potential risks.Clinically,monitoring should be strengthened based on time windows and population characteristics to optimize drug regimens.Countermeasure It is recommended to strengthen the full cycle monitoring of anti-tumor drugs,standardize the reporting of adverse reactions,and establish a multi-departmental collaborative research platform.

ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.

Objective To investigate the relationship between tooth loss and the occurrence of esophageal cancer in a natural village in Wenfeng District, Anyang City, Henan Province. Methods A prospective cohort study was conducted to observe the occurrence of tooth loss and esophageal cancer among the asymptomatic residents of the natural village for 16 years from January 2008 to July 2024. Data were analyzed by chi-square test, binary logistic regression, and restricted cubic spline. Results Among the total population of 711 cases, 136 cases were lost to follow-up and 575 cases were included in the final statistics, including 45 cases with esophageal cancer. Significant statistical difference was found between esophageal cancer patients with and without tooth loss (P<0.05). Logistic regression analysis showed that tooth loss was associated with the occurrence of esophageal cancer (OR=3.977, 95%CI: 1.543-10.255). After the adjustment for confounders, tooth loss remained significantly associated with the occurrence of esophageal cancer (OR=3.038, 95%CI: 1.035-8.914). A nonlinear dose-response relationship was observed between the number of teeth lost and the incidence of esophageal cancer. When the number of teeth lost was less than 12, the risk of esophageal cancer increased with the number of teeth lost. When more than 12 teeth were lost, the risk of esophageal cancer decreased as the number of teeth lost increased. Conclusion Tooth loss is a risk factor for the occurrence of esophageal cancer in this natural village. When the number of teeth lost is less than 12, the risk of esophageal cancer increases with the number of teeth lost.

Objective To evaluate answers to typical clinical questions related to neuro-ophthalmology generated by Artificial Intelligence(AI)Large Language Models(LLM)and to explore the performance of neuro-ophthalmology-related questions on LLM in a multidimensional manner using objective and expert assessment.Methods Multicenter,random-ized,cross-sectional pilot study.Thirty typical questions related to neuro-ophthalmology were selected based on four per-spectives:definition,etiology,clinical manifestations and signs,and treatment and prognosis,and were analyzed quantita-tively using Deepseek,Wenxin Yiyin 4.0,Doubao,and Kimi 1.5,which are four open-source LLMs in China,and quantita-tively analyzed with objective assessment;and quantitatively rated by three ophthalmologists using expert assessment for 120 answer texts.Three ophthalmology experts quantitatively scored the 120 answer texts.Three ophthalmologists quantita-tively scored the 120 answer texts.Level 3,5,and 4 Likert scales were developed according to the completeness,accura-cy,professionalism,relevance,and criticality of the question texts,respectively.The best-performing LLM was selected,and its performance was observed across the four types of questions.Additionally,three other experts assessed whether the best-performing one could be evaluated as a substitute for real-world doctor-patient communication.Results In the objective Chinese text reading difficulty analysis,the differences in total word count among the four LLMs were statistically significant(all P＜0.001).Of the four LLMs,Kimi 1.5 performed the best,with frequencies of 61％,29％,and 41％for the highest scores in completeness(3),accuracy and professionalism(5),and relevance and usefulness(4),respective-ly.Kimi 1.5 performed more consistently on the questions on the four areas of neuro-ophthalmologic disorders:definition,etiology,clinical manifestations and signs,treatment,and prognosis,with no between-group differences(P＞0.05).Con-clusion Chinese language LLMs have great potential in the clinical application of neuro-ophthalmology.Kimi 1.5 outper-forms other LLMs in terms of completeness,accuracy,professionalism,relevance,and usefulness,but it still cannot re-place real-world doctor-patient communication.There is a need to explore new diagnostic and therapeutic model of AI+physician in the future.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

Objective:To explore the clinical application value of ultrasound detection of endometrial blood flow perfusion in evaluating the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles.Methods:A case-control study of 226 patients underwent preimplantation genetic testing (PGT) in the Department of Reproductive Medicine of Chengdu Women's and Children's Central Hospital was conducted. Patients enrolled from December 2021 to August 2024 underwent three-dimensional ultrasound endometrial receptivity testing on the day before FET. According to the pregnancy outcomes, they were divided into clinical pregnancy group ( n=155) and non-pregnancy group ( n=71). The general characteristics and endometrial receptivity parameters were compared between the two groups. Binary logistic regression was used to analyze the factors affecting pregnancy. Results:There was no significant difference in age, proportion of primary infertility, anti-Müllerian hormone, and antral follicle count between the two groups (all P>0.05). The duration of infertility in the clinical pregnancy group [(2.79±2.45) years] was significantly lower than that in the non-pregnancy group [(3.44±1.68) years, P=0.046], the basal luteinizing hormone (LH) level in clinical pregnancy group [(4.37±3.02) U/L] was higher than that in the non-pregnancy group [(3.59±2.02) U/L, P=0.047]. On the day before embryo transfer, the single-plane endometrial blood flow branch in the pregnancy group (4.83±1.57) was more than that in the non-pregnancy group (3.44±1.51), the difference was statistically significant ( P=0.001). The clinical pregnancy group had significantly different endometrial morphology types A [5.2% (8/155)], B [25.8% (40/155)], and C [69.0% (107/155)] compared with the non-pregnancy group [16.9% (12/71), 33.8% (24/71), 49.3% (35/71), P=0.003], respectively, the number of peristalsis waves in the clinical pregnancy group [1(0, 2)] was less than that in the non-pregnancy group [1(0, 4), P=0.046]. There were no significant differences in endometrial thickness, peristaltic wave classification, endometrial volume, endometrial and subendometrial blood flow pulse index/resistance index between the two groups (all P>0.05). Binary logistic regression analysis showed that the endometrial blood flow branch, endometrial peristalsis and basal LH level were independent factors affecting the pregnancy outcome of patients underwent PGT during FET cycle ( OR=1.855, 95% CI: 1.478-2.327, P=0.001; OR=0.813, 95% CI: 0.667-0.990, P=0.040; OR=1.163, 95% CI: 1.000-1.351, P=0.049). Among them, the area under the receiver operating characteristic curve of endometrial blood flow branches for the prediction of PGT-FET pregnancy outcome was 0.725, P=0.001. Conclusion:Endometrial blood flow branch, which represents the intensity of blood perfusion, has a good clinical value in evaluating the pregnancy outcome during FET cycle.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.