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.

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.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

Ulcerative colitis （UC） is a refractory disease of the digestive system characterized by diverse etiologies， complex pathogenesis， a prolonged course， and frequent relapses. In recent years， the incidence of UC has been increasing annually， severely impairing patients' quality of life， posing a risk of malignant transformation that may threaten patients' lives， and resulting in a substantial medical burden. Traditional Chinese medicine （TCM） compound formulas， with their advantages of multi-component and multi-target actions， have become a new therapeutic option for UC. The NOD-like receptor pyrin domain-containing 3 （NLRP3） inflammasome is a core component of innate immunity， and its aberrant activation is closely associated with the onset and progression of UC， involving multiple processes such as inflammation and oxidative stress， and exhibiting crosstalk with pathways including nuclear factor-κB （NF-κB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and thioredoxin-interacting protein （TXNIP）. At present， NLRP3 has become one of the most intensely studied hotspots in UC-related research. Although increasing studies have focused on the regulation of the NLRP3 inflammasome by TCM compound formulas for UC treatment， challenges remain due to the complex pathogenesis of UC and the compositional diversity of TCM， hindering the realization of precision therapy. In this context， by reviewing literature from the past decade， this paper summarizes the activation process of NLRP3 and its relationship with UC， and elucidates the roles and mechanisms by which TCM compound formulas regulate the NLRP3 inflammasome and related signaling pathways， with a view to providing a reference for further research into the pathogenesis of UC， TCM treatment strategies， and their mechanisms of action.

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 predict the pregnancy probability of patients and provide clinical guidance,the factors that affect the pregnancy outcome of patients with endometriosis(EM)after operation by machine learning were explored.Methods The clinical data of 167 EM patients after conservative surgery were analyzed retrospectively.Boruta algorithm was used to screen the features with high ranking,and four machine learning models,namely random forest,decision tree,support vector machine(SVM)classifier and extreme gradient lifting(XGBoost)were constructed.The performance of the model is evaluated based on four indicators:accuracy,recall,accuracy and area under curve(AUC)of receiver operating characteristic.Shapley additive interpretation(SHAP)was used to visualize the contribution of each variable to the pregnancy outcome and the positive and negative directions.Results Age,body mass index(BMI),postoperative CA125,preoperative CA125,the course of opportune capsule,the course of dysmenorrhea,the score of dysmenorrhea symptoms,the score of pelvic positive signs,the score of TCM symptoms and menstrual cycle were the important characteristics in the top ranking.The decision tree model(accuracy:0.66,accuracy:0.63,recall:0.62,AUC:0.67,F1:0.60)had the best average classification performance.Based on the results of SHAP analysis,age,BMI index,postoperative CA125 level and Traditional Chinese medicine syndrome score had significant effects on the outcome.The higher the value,the lower the postoperative pregnancy rate.Conclusion Age,BMI,postoperative CA125 level and traditional Chinese medicine syndrome score of patients with endometriosis after combined drug therapy are the main evaluation indexes that affect the pregnancy outcome of patients with endometriosis after combined drug therapy.When the values of these four characteristics are high,patients are not advised to conceive naturally,and appropriate assisted reproductive technology should be selected as soon as possible.

Objective To explore the multimorbidity pattern and traditional Chinese medicine(TCM)syndrome characteristics of patients with adenomyosis(AM)and to provide insights and data support for medical treatment and comprehensive AM management.Methods By retrospectively analyzing multi-center,large-sample,nationwide cross-sectional survey data,patients were divided into a single AM group or a multimorbidity group based on whether they had other diseases.The prevalence rates of specific multimorbidity or a combination of multimorbidities were calculated respectively.Single-factor analysis was used to explore the influence of age,course of disease,education level,labor nature,monthly income,production history,abortion history,operation history,region,and TCM syndromes on multimorbidity in patients with AM.The multimorbidity patterns of patients with AM were explored using Apriori association rules,and the distribution characteristics of TCM syndromes in different multimorbidity patterns were explored.Results Among 1,814 patients with AM,1,429 were in the multimorbidity group(prevalence of 78.78％).Compared with the single AM group,the patients in the multimorbidity group had a long disease course,high academic qualifications,jobs that mostly involved sitting,a history of surgery,and were primarily concentrated in the north(P＜0.05).The proportion of patients with qi stagnation and blood stasis syndrome decreased,whereas the proportion of patients with kidney deficiency and blood stasis syndrome increased.Ten multimorbidity association rules were sorted according to the confidence level,and the first place of binary association rules was breast nodule to breast hyperplasia,and the first place of ternary association rules was hysteromyoma,breast nodule to breast hyperplasia.Comprehensive support and confidence level,in the binary association rules,the strong association rule was breast nodule to thyroid nodule,and sub-strong association rule was thyroid nodule to breast hyperplasia;In the ternary association rules,the strong association rule was hysteromyoma,breast nodules to breast hyperplasia,and sub-strong association rule was endometriosis,thyroid nodules to breast hyperplasia.There was no significant difference in the distribution of TCM syndromes in AM patients with different binary and ternary multimorbidity patterns.Conclusion Patients with AM have different multimorbidity patterns,and the TCM syndromes of patients with AM under different multimorbidity patterns have different characteristics.The management system of AM multimorbidity should be further developed to ensure more comprehensive and standardized health management for patients with AM.

Objective:To compare the Kadish T staging, AJCC T staging, and Dulguerov T staging system in terms of their impact on surgical treatment selection and survival prognosis in patients with olfactory neuroblastoma (ONB).Methods:The cases of pathologically confirmed ONB from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 were collected and screened. Tumors were staged according to Kadish staging system, AJCC T staging and Dulguerov T staging guidelines. Kaplan-Meier analysis was used to calculate 5-and 10-year overall survival rates for different stages, and the log-rank test was used to detect statistically significant differences. Multivariate analysis was performed using Logistic regression and Cox regression models to explore factors influencing surgical treatment choices and prognosis in ONB patients.Results:A total of 519 ONB patients with complete data available for analysis were included in the study. Multivariate analysis revealed that tumor staging, age, and marital status were closely associated with surgical treatment selection. The 10-year survival rates for patients in stage A, B, and C were 74.1%, 68.7%, 55.0%, respectively. The multivariate analysis failed to show a significant prognostic gradient between adjacent stages in any of the three staging systems.Conclusions:The selection of surgical treatment for ONB is influenced by clinical characteristics such as tumor stage and age. The commonly used Kadish, AJCC T, and Dulguerov T staging systems do not significantly differentiate prognosis between adjacent stages, highlighting the need for the development of a more accurate and comprehensive staging system.

Purpose To explore the relationship between semi-quantitative parameters maximum standard uptake value(SUVmax)and target-background ratio(TBR)of 18F-FDG PET/CT imaging and the activity of Takayasu arteritis.Materials and Methods A total of 110 patients with Takayasu arteritis from February 2016 to December 2022 in the First Affiliated Hospital of Zhengzhou University who underwent 18F-FDG PET/CT images were retrospectively reviewed.All Takayasu arteritis patients were divided into active(92 cases)and inactive groups(18 cases)according to Kerr score.The region of interest technique was used to measure the SUVmax of the arterial wall,and compares the SUVmax with the average SUV in the center of the inferior vena cava and the maximum SUV measured in the right lobe of the liver to obtain TBRblood pool and TBRliver.The diagnostic efficacy of SUVmax,TBRblood pool and TBRliver in Takayasu arteritis activity was compared using the receiver operating characteristic curve.The relationship between PET/CT parameters and Kerr score,erythrocyte sedimentation rate and C-reactive protein was evaluated.Results SUVmax,TBRblood pool and TBRliver in the active group were higher than those in the inactive group[3.70(3.03,5.18)vs.1.45(1.38,1.53),2.50(1.93,3.88)vs.0.91(0.79,1.16)and 1.37(1.00,1.96)vs.0.44(0.39,0.63);Z=5.510-5.900,all P<0.001],respectively.A SUVmax level of 2.65 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 83.7%,specificity 100%and area under the curve 0.91).A TBRblood pool level of 1.63 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 83.7%,specificity 94.4%and area under the curve 0.93).A TBRliver level of 0.81 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 87.0%,specificity 100%and area under the curve 0.94).SUVmax,TBRblood pool,TBRliver were all positively correlated with the Kerr score(r=0.88,0.89.0.90,all P<0.001),among which the correlation coefficient between TBRliver and the Kerr score was the highest.Conclusion SUVmax,TBRblood pool and TBRliver can evaluate disease activity in Takayasu arteritis patients,with TBRliver being the best.