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.

AIM:To investigate the expression of centromere protein-H(CENP-H)in adrenocortical carcino-ma(ACC)and its relationship with disease progression and prognosis,and to explore the impact of CENP-H gene knock-down on the viability and migration of ACC cells.METHODS:The mRNA expression level of CENP-H in 76 ACC pa-tients and 128 healthy controls,and its correlations with tumor stages and prognosis were analyzed by GEPIA2 database.The mRNA expression of CENP-H in different stages of ACC and its correlation with disease prognosis were further ana-lyzed by ULCAN database.The protein expression of CENP-H was examined by immunohistochemical staining of paraffin-embedded ACC and normal adrenal gland specimens.Knockdown of CENP-H by siRNA(siCENP-H)was performed in human ACC cell line H295R.The viabilty of H295R cells transfected with siCENP-H or siNC was measured by CCK-8 as-say,the cell migration was detected by wound-healing assay,and the protein levels of CENP-H,p-ERK1/2,t-ERK1/2,p-P38,t-P38,p-JNK1/2 and t-JNK1/2 were detected by Western blot.RESULTS:The mRNA level of CENP-H was signifi-cantly higher in ACC than that in normal controls,and was correlated with tumor stages and prognosis.The protein level of CENP-H was significantly higher in ACC specimens than that in normal adrenal gland.Knockdown of CENP-H in H295R cells resulted in decreased cell viability and migration.The protein levels of p-P38 and p-JNK1/2 were decreased in si-CENP-H group.CONCLUSION:CENP-H is highly expressed in ACC,and is correlated with tumor stages and poor prognosis.Knockdown of CENP-H can inhibit the viability and migration of ACC cells,and its mechanism may related to inactivation of P38 and JNK signaling pathways.

The disease spectrum of ABCB4 gene mutation involves various diseases such as progressive familial intrahepatic cholestasis type 3 （PFIC3）， gallstone disease， intrahepatic cholestasis of pregnancy， portal hypertension， liver cirrhosis， and even primary hepatic and biliary malignancies. A young male patient was admitted to Department of Hepatobiliary Medicine， Eastern Hepatobiliary Surgery Hospital， and was initially diagnosed with liver cirrhosis and gallstones， and he was planned to receive laparoscopic cholecystectomy. Preoperative examination showed abnormal liver function， liver cirrhosis， splenomegaly， and mild esophageal varices， and next-generation sequencing was performed to make a confirmed diagnosis of ABCB4 gene mutation-associated liver cirrhosis with gallstones. The liver function of the patient gradually returned to normal after cholagogic treatment with ursodeoxycholic acid capsules.

BACKGROUND:Diabetic nephropathy is an important cause of end-stage renal disease,and intestinal barrier damage plays an important role in the occurrence and development of diabetic nephropathy. OBJECTIVE:To observe the protective effect of human umbilical cord mesenchymal stem cells on the intestinal barrier in rats with diabetic nephropathy. METHODS:Thirty 8-week-old male SD rats were randomly assigned to healthy control group,model group and human umbilical cord mesenchymal stem cell group,with 10 rats in each group.Rats in the human umbilical cord mesenchymal stem cell group were injected with 1×106 human umbilical cord mesenchymal stem cells through the tail vein once a week for 4 weeks after the model establishment of diabetic nephropathy.Rats in the healthy control group and the model group were injected with an equal volume of PBS at the same time.1 week after the last injection,the histomorphological changes in the kidney and colon were observed under a light microscope.The expressions of ZO-1 and Occludin in the colon tissue of rats were detected by immunohistochemistry.Serum D-lactic acid and lipopolysaccharide levels were detected by ELISA.In addition,the distribution of human umbilical cord mesenchymal stem cells labeled with DiR dye in rats was observed by in vivo imaging system.The expression of human mesenchymal stem cell surface marker antigens CD44 and CD90 in colon tissue was detected by immunohistochemistry. RESULTS AND CONCLUSION:(1)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly inhibited the increase of urea nitrogen,serum creatinine,24-hour urine protein level and urinary albumin/creatinine ratio in diabetic nephropathy rats(all P<0.05).(2)The expression of human mesenchymal stem cell surface markers CD44 and CD90 was found in the colon of diabetic nephropathy rats.(3)Compared with the healthy control group,the expression levels of tight junction proteins Occludin and ZO-1 in the colon tissue of the model group were significantly reduced,while the expressions of Occludin and ZO-1 were significantly increased after treatment with human umbilical cord mesenchymal stem cells.(4)Compared with the model group,human umbilical cord mesenchymal stem cell transplantation significantly reduced serum D-lactic acid and lipopolysaccharide levels in diabetic nephropathy rats.(5)The results suggest that human umbilical cord mesenchymal stem cells may protect the intestinal barrier function by enhancing the expression of intestinal tight junction proteins in diabetic nephropathy rats.

Objective:To explore the risk factors for malnutrition after a tracheotomy and to construct a predictive model useful for its prevention through early intervention.Methods:Clinical data describing 440 tracheotomy patients were subjected to a retrospective analysis. The variables examined were age, sex, etiology, Glasgow Coma Score (GCS), activities of daily living (ADL) score, age-corrected Charlson comorbidity index (aCCI), food intake, swallowing function, incidence of infections, as well as any history of diabetes mellitus, hypertension, smoking or alcohol consumption. Patients identified as being at risk of malnutrition (NRS-2002≥3) were screened using the Nutritional Risk Screening tool (NRS-2002) and the European Society of Clinical Nutrition and Metabolism′s ESPEN2015 criteria. The subjects were thus categorized into a malnutrition group of 343 and a control group of 97. Unifactorial and multifactorial logistic regression analyses were performed, and stepwise regression was applied to include the factors found significant in the unifactorial analysis into the multifactorial logistic regression analysis, and to construct a column-line graph prediction model. The clinical utility of the model was assessed by applying the receiver operator characteristics (ROC) curves, calibration plots and decision curve analysis (DCA).Results:Of the 440 persons studied, 343 (78%) were malnourished. The multivariate logistic regression analysis showed that pulmonary infection, dysphagia, low GCS score and high aCCI score were significant risk factors for malnutrition after a tracheotomy. A prediction nomograph was constructed. After fitting and correcting, the area under the curve (AUC) of the prediction model′s ROC curve was 0.911, the specificity was 80.4%, and the sensitivity was 91.3%. That was significantly higher than the AUCs for pulmonary infection (0.809), dysphagia (0.697), aCCI (0.721) and GCS (0.802). Bootstrap self-sampling was used to verify the model internally. After 1000 samples the average absolute error between the predicted risk and the actual risk was 0.013, indicating good prediction ability. The DCA results demonstrated that the model has substantial clinical applicability across a range of nutritional interventions, particularly for threshold probability values ranging from 0 to 0.96.Conclusion:Pulmonary infection, dysphagia, low GCS score, and high aCCI score are risk factors for malnutrition among tracheotomy patients. The nomogram model constructed in this study has good predictive value for the occurrence of malnutrition among such patients.

【Objective】 A new type of testicular hydrocele reversal resection is described under the concept of trans-interfascial plane surgery, in order to improves the understanding of the anatomical level of testicular hydrocele surgery and to optimize the surgical approach. 【Methods】 During Jan. and June 2021, 15 patients with primary testicular hydrocele were treated with hydrocelectomy and gubernaculum preservation.Demographic information, indications of treatment, success rate and complications were collected.The anatomical structures were analyzed using intraoperative findings and photographs. 【Results】 All operations of 15 patients were successful, with the surgery time of 25-48 minutes, with an average of (34.0±6.2) minutes.No patients experienced scrotal hematoma or incision infection.There were no relapses during the 3-month follow-up after surgery.The anatomical points observed during surgery were as follows: we further confirmed that the internal spermatic fascia completely surrounded the testis, epididymis, and the spermatic cord; this layer was an avascular plane, the cremaster muscle and fascial layer between the internal and external spermatic fasciae were absent; intraoperative preservation of the gubernaculum helped to fix the testicles in its natural position. 【Conclusion】 Our novel technique of hydrocelectomy is reliable, and the precise anatomical description of the concept of trans-interfascial plane surgery can help to improve the related surgical techniques.

Objective To investigate the epidemiological characteristics and trends in the prevalence of tuberculosis among in the six urban districts of Tianjin from 2014 to 2023, so as to provide scientific basis for the prevention and control of tuberculosis. Methods Data on the occurrence of new tuberculosis cases among in the six urban districts of Tianjin from 2014 to 2023 were collected through the Tianjin Infectious Disease Report Information Management System, and the epidemiological characteristics of new tuberculosis cases were descriptively analyzed. Then the Average Annual Percentage Change (AAPC) statistics were used to characterize the magnitude and direction of trends. Results A total of 17 818 tuberculosis cases were reported in the six urban districts of Tianjin from 2014 to 2023 , with an average annual reported prevalence rate of 25.61/100 000. The prevalence rate of tuberculosis in the six urban districts of Tianjin from 2014 to 2023 showed a decreasing trend, reporting a prevalence rate of 35.47/100 000 in 2014 and 22.72/100 000 in 2023, and AAPC is -4.86% (-7.13% to -1.56%) , with statistical difference (P<0.05). In terms of gender, the overall prevalence rate of tuberculosis was 31.17/100,000 in males and 19.47/100,000 in females, with statistical difference (χ²=276.12 , P<0.05). The incidence in people younger than 25 years and older than 55 years is on the rise from 2014 to 2023. In terms of occupation, household duties, unemployed people, retired people and office clerks showed a high prevalence rate of tuberculosis. Conclusion The overall prevalence of adult tuberculosis in the six urban districts of Tianjin from 2014 to 2023 shows a decreasing trend, whereas the prevalence rate of males is higher than that of females, and the elderly, families, unemployed people, retirees and office clerks are high-risk groups, so targeted preventive and control measures, health education and screening should be strengthened.

Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

Objective To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization(MR)approach.Methods We obtained data pertaining to colorectal cancer from Genome-Wide Association Study(GWAS)datasets and used 91 inflammatory protein markers as the exposure variables.A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk.The robustness of the results was evaluated through heterogeneity,pleiotropy,and sensitivity analyses using 5 MR models:Inverse Variance Weighted(IVW),Weighted Median,MR Egger,Simple Mode,and Weighted Mode.We examined the mRNA expressions of PD-L1,AXIN1,and β-NGF using RT-qPCR in 86 untreated patients with colorectal adenocarcinoma admitted in Nanfang Hospital between December,2021 and December 2023,and analyzed their correlation with the clinical characteristics of the patients.Results Using the IVW model,MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1(OR=0.866,95%CI:0.754-0.994,P=0.040),β-NGF(OR=0.914,95%CI:0.843-0.990,P=0.028;OR=0.884,95%CI:0.784-0.998,P=0.047 using Weighted Median model),and PD-L1(OR=0.903,95%CI:0.824-0.989,P=0.028).No significant heterogeneity or pleiotropy was observed,indicating good stability of the results.Sensitivity analysis confirmed the reliability of the findings.The clinical study demonstrated a significant correlation between PD-L1 expression and TNM staging,particularly in stage IV patients(P=0.007).AXIN1 and β-NGF expression levels were significantly correlated with the degree of tumor differentiation,and their expressions were higher in poorly differentiated samples(P<0.001).Conclusion Lowered expressions of inflammatory protein markers AXIN1,β-NGF,and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation.These markers may thus serve as potential targets for colorectal cancer treatment and prevention.

Objective:To investigate the effects of acetabular cup positions on the acetabular side stress in hip dysplasia after total hip arthroplasty (THA) using finite element analysis.Methods:Data were obtained from a 36-year-old female patient with developmental dysplasia of the hip. Three-dimensional finite element models were established for different acetabular cup positions using finite element analysis. Each model was categorized based on the center of rotation into four groups: anatomical rotation center, high rotation center, lateralized rotation center, superior-lateral rotation center. ANSYS software applied loads to the model to simulate the stress around the acetabulum in standing (588 N vertical stress) and walking conditions ( X=325 N, Y=-195 N, Z=1 462.5 N). Quantitative analyses of the relative displacement and stress at the acetabular-bone interface were conducted for each region under the two different loading conditions in all eight models. Results:In the standing position with a cup coverage of 90%, the relative displacement at the acetabular-bone interface was: 45.16 μm for the anatomical rotation center group, 47.57 μm for the high rotation center group, 77.27 μm for the lateralized rotation center group, and 96.13 μm for the superior-lateral rotation center group. Acetabular stress values were 9.07 MPa for the anatomical rotation center group, 11.23 MPa for the high rotation center group, 10.88 MPa for the lateralized rotation center group, and 17.75 MPa for the superior-lateral rotation center group. With a cup coverage of 70%, the relative displacements were 64.15, 65.71, 104.10, and 144.53 μm for the respective groups. The corresponding stresses were 9.30, 11.31, 13.98, and 21.45 MPa. In the walking state with a cup coverage of 90%, the relative displacements at the acetabular-bone interface were 189.67 μm for the anatomical rotation center group, 173.55 μm for the high rotation center group 311.03 μm for the lateralized rotation center group, and 572.93 μm for the superior-lateral rotation center group. The stresses were 39.92, 37.33, 47.92, and 71.94 MPa, respectively. With a cup coverage of 70%, the relative displacements were 239.09 μm for the anatomical rotation center group, 248.83 μm for the high rotation center group, 381.84 μm for the lateralized rotation center group, and 1105.90 μm for the superior-lateral rotation center group. The corresponding stresses were 40.62, 58.42, 56.26, and 3,606.30 MPa.Conclusion:With cup coverage at 70% and 90%, the high rotation center and anatomical rotation center exhibited lower and less frequent relative displacements at the acetabular-bone contact surface.