Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

Objective To explore the clinical features, diagnosis, treatment and prognosis of testicular Ewing sarcoma(ES), so as to enhance the understanding and differential diagnosis of this disease. Methods A retrospective analysis was conducted on the clinical manifestations, auxiliary examinations and pathological findings of a case of left-sided ES treated at our hospital, supplemented by a review of relevant literature. Results A 24-year-old male patient presented with left testicular enlargement with pain. Magnetic resonance imaging suggested a neoplastic lesion, with a high likelihood of testicular germ cell tumor. A radical left orchiectomy was performed. Postoperative pathology revealed testicular ES. The patient subsequently completed 8 cycles of VDC/IE chemotherapy and showed no evidence of recurrence at 10 months of follow-up. Analysis of literature on 5 previously reported cases of testicular ES had testicular enlargement as the primary presentation. All patients underwent surgery and 4 received adjuvant therapy. Follow-up revealed 1 death at 9 months postoperatively, with no recurrence or progression seen in the remainder. Conclusion ES occurring in the testis is extremely rare.Testicular ES is a poorly differentiated small round-cell malignant tumor that primarily presents as testicular enlargement. Current treatment mainly surgical resection combined with adjuvant chemotherapy.

Objective To explore the characteristics and temporal trends of renal cancer burden among Chinese adolescents and young adults(AYA), and predict its future epidemic situation, so as to provide evidence for formulating public health policies and reducing the disease burden.Methods Epidemiological data of renal cancer in Chinese AYA(15-39 years)from 1990 to 2021 were obtained from the Global Burden of Disease(GBD)2021 database. The current status and trends of renal cancer in this population were analyzed. The incidence and mortality trends of renal cancer in AYA over the next 15 years was predicted with ARIMA model. The impacts of smoking and body mass index(BMI)on the disease burden were evaluated. Results In 2021, the incidence(1.12/100000), prevalence(8.61/100000), mortality(0.19/100000), and disability-adjusted life years(DALYs)(11.37/100000 person-years)of renal cancer in Chinese AYA were significantly higher than those in 1990 and above the global average. All burden indicators and their increases were higher in males than in females, and the burden accelerated after 30 years of age. The incidence rose steadily from 2003 to 2021(APC=3.95), while the mortality increased significantly from 2013 to 2021(APC=2.40). The burden attributed to high BMI continued to rise, and the smoking-attributable fraction in males first increased then decreased. ARIMA predicted that the incidence of renal cancer in Chinese AYA males would accelerate, while the mortality in both genders would stabilize. Conclusion The burden of renal cancer in Chinese AYA shows a significant upward trend. Males and people over 30 years old are key targets for prevention and control. Strengthening the management of risk factors(smoking, high BMI)and promoting early diagnosis and treatment are essential to reduce the disease burden.

Objective To screen the aging-related genes associated with prognosis in clear cell renal cell carcinoma (ccRCC), construct a prognostic model to optimize risk stratification, explore the underlying mechanisms, and provide reference for individualized diagnosis and treatment of this disease.Methods RNA sequencing data, clinical data, and aging-related genes of ccRCC were obtained from databases.After differentially expressed genes were screened, a prognostic model was constructed using Cox regression.The performance of the model was evaluated with Kaplan-Meier curves and receiver operating characteristic (ROC) curves, and validated with clinical features.Key genes were verified with immunohistochemistry.Results A total of 70 differentially expressed genes were identified, including IFI16, PECAM1, and ABCB1 as key genes, and a model formula was constructed.Internal and external validations showed that the survival rate of the high-risk group was significantly lower, with the area under the ROC curve (AUC)＞0.6.The risk score was correlated with clinical features.IFI16 was highly expressed in cancer tissues and associated with poor prognosis.Conclusion The prognostic model constructed in this study has good performance.Integrating clinical features, it can improve the accuracy of prognosis assessment of ccRCC.

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

Cardiotoxicity is a critical issue in drug development that poses serious health risks,including potentially fatal arrhythmias.The human ether-à-go-go related gene(hERG)potassium channel,as one of the pri-mary targets of cardiotoxicity,has garnered widespread attention.Traditional cardiotoxicity testing methods are expensive and time-consuming,making computational virtual screening a suitable alter-native.In this study,we employed machine learning techniques utilizing molecular fingerprints and descriptors to predict the cardiotoxicity of compounds,with the aim of improving prediction accuracy and efficiency.We used four types of molecular fingerprints and descriptors combined with machine learning and deep learning algorithms,including Gaussian naive Bayes(NB),random forest(RF),support vector machine(SVM),K-nearest neighbors(KNN),eXtreme gradient boosting(XGBoost),and Trans-former models,to build predictive models.Our models demonstrated advanced predictive performance.The best machine learning model,XGBoost Morgan,achieved an accuracy(ACC)value of 0.84,and the deep learning model,Transformer_Morgan,achieved the best ACC value of 0.85,showing a high ability to distinguish between toxic and non-toxic compounds.On an external independent validation set,it achieved the best area under the curve(AUC)value of 0.93,surpassing ADMETlab3.0,Cardpred,and CardioDPi.In addition,we explored the integration of molecular descriptors and fingerprints to enhance model performance and found that ensemble methods,such as voting and stacking,provided slight improvements in model stability.Furthermore,the SHapley Additive exPlanations(SHAP)explanations revealed the relationship between benzene rings,fluorine-containing groups,NH groups,oxygen in ether groups,and cardiotoxicity,highlighting the importance of these features.This study not only improved the predictive accuracy of cardiotoxicity models but also promoted a more reliable and scientifically interpretable method for drug safety assessment.Using computational methods,this study facilitates a more efficient drug development process,reduces costs,and improves the safety of new drug candidates,ultimately benefiting medical and public health.

OBJECTIVES: This study aimed to explore the active components, potential targets, and mechanism of Cnidii Fructus in the treatment of periodontitis with osteoprosis through network pharmacology, molecular docking, and molecular dynamics simulation technology. METHODS: The main chemical constituents and targets of Cnidii Fructus were screened using the TCMSP and SwissTargetPrediction databases, as well as literature reports. Targets of periodontitis and osteoporosis were predicted using different databases. The intersection targets of Cnidii Fructus, periodontitis, and osteoporosis were obtained using Venny 2.1. The protein-protein interaction network was formed on the STRING platform. Cytoscape 3.9.1 was used to construct the active component-intersection target interaction network, perform the topological analysis, and screen key targets and core active components. Furthermore, the Metascape database was used to perform gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis on the intersection targets. The top five key targets and core active components were selected as receptor proteins and ligand small molecules. Discovery Studio 2019 was used to dock ligands and receptors and visualize the docking results. Molecular dynamics simulation was conducted using Gromacs2022.3 to assess the stability of the interactions between the core active components and the main targets. RESULTS: A total of 20 potential active ingredients of Cnidii Fructus were screened, and 116 targets of Cnidii Fructus were obtained for treating periodontitis and osteoporosis. GO and KEGG analyses of the 116 targets showed that Cnidii Fructus may play a therapeutic role through the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathways. Molecular docking showed that the core constituents were well bound to the main targets. Molecular dynamics simulations confirmed the stability of the Diosmetin-AKT1 complex system. CONCLUSIONS The preliminary discovery of the potential molecular pharmacological mechanism of Cnidii Fructus extract in the targeted treatment of periodontitis with osteoporosis through a multi-component, multitarget, and multi-pathway approach can serve as a theoretical foundation for future drug-development research and clinical application.
Molecular Docking Simulation ; Molecular Dynamics Simulation ; Network Pharmacology ; Periodontitis/complications* ; Drugs, Chinese Herbal/chemistry* ; Osteoporosis/complications* ; Humans ; Protein Interaction Maps ; Cnidium/chemistry*

Objective To screen specific antibodies to Helicobacter pylori(H.pylori)in serum,and establish antibody panels and discrimination models for different infection status,which are non-invasive and suitable for gastric cancer screening in Chinese population.Methods A total of 300 subjects with different H.pylori statuses were enrolled depending on an endoscopy screening cohort in a high-risk area of gastric cancer,including current,past,and negative infections.The recomLine Helicobacter IgG 2.0 immunoblotting assay was used to analyze and screen 10 H.pylori specific antibodies in serum samples.Results A total of nine antibody reactivity against CagA,VacA,GroEL,FliD,HpaA,gGT,HtrA,NapA,and CtkA showed significant differences among different H.pylori infection status groups(all P＜0.05).A panel comprising the nine antibodies distinguished exposure subjects to H.pylori(current and past infections)from negatives,with an area under the curve(AUC)of 0.935(95%CI:0.907-0.963).The combination of four antibodies(CagA,GroEL,FliD,and gGT)may help to discriminate current and past infection subjects,with an AUC of 0.927(95%CI:0.891-0.964).Conclusion The antibody panels and discriminant models for H.pylori infection status established in the present study may provide a potential and non-invasive screening method for the development of precise gastric cancer prevention strategies.

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.