Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Objective To investigate the expression characteristics of c-MET protein in colorectal cancer (CRC) and its associations with clinicopathological parameters, MET gene amplification status, and prognosis, and to evaluate the concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) detection strategies, thereby providing evidence for patient selection for MET-targeted therapy. Methods A total of 193 formalin-fixed paraffin-embedded (FFPE) tissue samples from CRC patients were collected. Immunohistochemistry (IHC) was used to detect c-MET protein expression, and fluorescence in situ hybridization (FISH) was performed to evaluate MET gene amplification status. The associations between c-MET protein expression and clinicopathological characteristics, including KRAS, NRAS, and BRAF mutation status, as well as progression-free survival (PFS), were analyzed. The concordance between IHC and FISH detection results was also evaluated. Results c-MET protein expression was significantly higher in tumor tissues than in adjacent normal tissues (P<0.05). Significant differences in c-MET expression were observed between primary tumors and liver or peritoneal/pelvic metastatic lesions (P<0.05). The proportion of high c-MET expression was significantly higher in KRAS-mutant patients than in KRAS wild-type patients (41.38% vs. 16.92%, P<0.05). The MET gene amplification rate was 8.29% (16/193), including clustered or diffuse amplification in 1.55% (3/193) and heterogeneous amplification in 6.74% (13/193). No MET exon 14 skipping mutation or amplification was detected by next-generation sequencing (NGS). Using an IHC H-Score≥150 as the threshold, the positive percent agreement (PPA) between IHC-detected c-MET protein expression and FISH-detected MET gene amplification was 100%. All clustered MET amplification regions exhibited diffuse strong c-MET expression (IHC 3+). No statistically significant association was observed between c-MET expression level and PFS (P>0.05). Conclusion High c-MET expression may represent a potential therapeutic target for KRAS-mutant CRC patients. An H-Score ≥150 is recommended as the initial screening threshold to rapidly identify patients suitable for MET-targeted therapy, with FISH testing when necessary. Diffuse strong c-MET expression (IHC 3+) shows high concordance with clustered MET gene amplification.

Objective To explore the relationship between the degree of compression and shape grading of the cerebral cistern ambiens in hypertensive cerebral hemorrhage(HCH)patients after neural endoscopic intracranial hematoma evacuation(NEIHE)and prognosis.Methods 246 HCH patients who underwent NEIHE surgery from January 2020 to June 2023 were selected as the research subjects.According to the postoperative 6 month Glasgow outcome score(GOS),the patients were divided into good prognosis group(n=158)and poor prognosis group(n=88).Hierarchical regression model was used to analyze the relationship between clinical pathological features and the degree of compression and shape grading of the cerebral cistern ambiens.Multivariate logistic regression model was used to analyze the independent risk factors affecting the poor prognosis of patients with HCH after NEIHE,and a prediction model was constructed.Receiver operating characteristic curve(ROC curve)was drawn with poor prognosis as the outcome variable.Area under the curve(AUC),integrated discrimination improvement(IDI)and net reclassification improvement(NRI)of different prediction models were compared.Hosmer-Lemeshow was used to test the goodness of fit.Generalized additive model(GAM)was used to analyze the relationship between GOS and related factors.Results Compared with the good prognosis group,the poor prognosis group had more preoperative blood loss,lower preoperative Glasgow coma score(GCS),and higher proportion of patients with midline deviation,hypertension history ≥10 years,hemorrhage breaking into the brain ventricle,and operation time in the late stage,the differences were statistically significant(P＜0.05).Compared with the good prognosis group,the proportions of patients with ipsilateral and contralateral cerebral cistern ambiens compression of 3 to 4 points and the morphological classification of cerebral cistern ambiens of grade V in the poor prognosis group were higher,and the differences were statistically significant(P＜0.05).The location of bleeding,midline deviation,and intracranial pressure all had an impact on the degree of compression and morphological grading of the cerebral cistern ambiens,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis(model 2:including the degree of compression and shape grading of the cerebral cistern ambiens)showed that midline deviation,history of hypertension ≥10 years,preoperative bleeding volume＞37 mL,bleeding into the brain ventricles,preoperative GCS＜7 points,late surgical timing,degree of compression of the cerebral cistern ambiens(3 to 4 points on the same side of hematoma,3 to 4 points on the opposite side of hematoma),and grade V morphology were all risk factors influencing the poor prognosis of patients with HCH after NEIHE(P＜0.05).After incorporating the degree of compression and morphological grading of the cerebral cistern ambiens into model 1(excluding the degree of compression and shape grading of the cerebral cistern ambiens),the AUC increased to 0.812(95％CI:0.763～0.872),and both the IDI(0.081,95％CI:0.049～0.095)and NRI(0.611,95％CI:0.510～0.674)of the model improved,with statistically significant differences(P＜0.05).Compared with model 1,model 2 showed an increase in AUC(0.826,95％CI:0.771～0.863),IDI(0.085,95％CI:0.052～0.110),and NRI(0.628,95％CI:0.510～0.709),with statistically significant differences(P＜0.05).The Hosmer-Lemeshow test showed that model 2(P=0.878)had a better fit for predicting poor prognosis than model 1(P=0.691).GAM analysis showed that the higher the degree of compression and morphological grading of the cerebral cistern ambiens,the lower the GOS,and the difference was statistically significant(P＜0.05).ROC curve analysis showed that the combined application of degree of compression and morphological grading of the cerebral cistern ambiens had a high predictive value for poor prognosis,with AUC of 0.935(95％CI:0.890～0.971),sensitivity of 70.26％,and specificity of 93.84％.Conclusion The degree of compression and shape changes of the cerebral cistern ambiens in HCH patients after NEIHE are closely related to prognosis,and the combined application has certain predictive value for poor prognosis.The location of bleeding,midline deviation,intracranial pressure,and other factors significantly affect the compression degree and shape change of the cerebral cistern ambiens.

Background and Aims:Extrahepatic cholangiocarcinoma(ECCA)is a malignancy with insidious onset,strong invasiveness,and poor prognosis,characterized by a high postoperative recurrence rate and a 5-year overall survival of less than 20％.Most existing prognostic models are based on the Cox proportional hazards model,which is limited by the proportional hazards assumption and linearity constraints.The random survival forest(RSF)model,a novel machine learning algorithm,can capture complex interactions and nonlinear effects among variables;however,its application in ECCA remains scarce.Therefore,this study developed a prognostic model for ECCA patients after radical resection using the RSF algorithm,aiming to provide precise and individualized prognostic assessments and support clinical decision-making.Methods:A total of 515 postoperative ECCA patients from the SEER database(2016-2021)were retrospectively enrolled and randomly divided into a training set(n=361)and a test set(n=154).Demographic and clinical variables were collected.Cox models were developed using univariate and multivariate regression,while RSF models were constructed using variable importance(VIMP)and minimal depth methods.Model performance was evaluated using the concordance index(C-index),time-dependent area under the curve(AUC),Brier scores,calibration plots,and decision curve analysis.Survival differences were assessed using Kaplan-Meier analysis,and interpretability was enhanced through the use of SurvSHAP and SurvLIME.Results:Multivariate Cox regression identified seven independent prognostic factors:age,race,income,T stage,N stage,tumor size,and chemotherapy.The RSF model selected four key predictors:age,tumor size,lymph node positive rate,and chemotherapy.In the test cohort,the RSF model achieved a C-index of 0.751,outperforming the Cox model(0.711).The RSF model yielded AUCs of 0.843,0.749,and 0.814 at 1,2,and 3 years,respectively,with superior calibration,overall performance,and net clinical benefit.Nonlinear associations were observed for lymph node positive rate,age,and tumor size,while chemotherapy was associated with reduced mortality risk.Stratified survival curves indicated poorer prognosis in patients without chemotherapy,lymph node positive rate＞0.1,age＞70 years,or tumor size＞20 mm.Conclusion:The RSF model,based on only four readily available clinical variables,demonstrated superior predictive performance compared with the Cox model.It provides a reliable tool for individualized prognosis and postoperative management in ECCA patients.The integration of interpretability frameworks further enhances its clinical applicability,offering potential to improve survival outcomes and quality of life.

Urothelial carcinoma (UC), including bladder urothelial carcinoma and upper tract urothelial carcinoma (UTUC), is the most common malignant tumor in the urinary system. Traditional cell line models fall short in simulating its tumor microenvironment and in vivo behavior. Patient-derived organoid (PDO) models offer a new way to overcome these shortcomings. This paper reviews the construction techniques of PDO models in UC, their biological simulation capabilities, and their applications in preclinical research. It also analyzes the technical limitations of these models. PDO models can retain the histological, genomic, and transcriptomic features of the parent tumor and accurately simulate the tumor microenvironment and biological behavior. They have been widely used in bladder cancer research, providing a precise platform for drug screening, personalized treatment, and immunotherapy evaluation. However, their use in UTUC research is still in its infancy. In the future, through technological optimization, PDO models are expected to enhance their value in UC research, advancing precision medicine research and clinical translation.

Objective:To investigate the clinical outcomes of nephron-sparing surgery (NSS) for tuberous sclerosis complex(TSC) -associated renal angiomyolipoma (RAML). Methods:This retrospective case-series study analyzed the clinical data of 15 TSC-RAML patients who underwent NSS at the Department of Urology, Peking Union Medical College Hospital between April 2013 and July 2024. The cohort included 4 males and 11 females. The age at TSC diagnosis was (28.5±14.5) years (range: 5 to 62 years), and the age at first surgery was (33.3±10.8) years (range: 18 to 62 years). The maximum tumor diameter( M(IQR)) was 6.4(7.9)cm (range: 3.5 to 31.5 cm). Patient baseline characteristics, surgical approach, TSC-RAML staging, imaging findings, and laboratory data were collected. Relationships between variables were analyzed using Generalized Estimating Equations with post-hoc tests. Results:A total of 18 surgical procedures were performed on the 15 patients. These included 7 open surgeries, 9 laparoscopic surgeries, and 2 laparoscopic procedures converted to open surgery. The mean preoperative serum creatinine level was (70.2±14.2) μmol/L (range: 50 to 101 μmol/L), which increased to (99.2±29.8) μmol/L (range: 47 to 171 μmol/L) on postoperative day 1. However, at one year postoperatively, serum creatinine was (76.8±13.5)μmol/L (range: 55 to 106 μmol/L),showed no significant difference from preoperative levels ( P>0.05). At the 6-month postoperative follow-up, the Utrecht Interventional Classification stage for all treated tumors had decreased to grade 1 or 2. At the 12-month follow-up (available for 13 patients), 11 patients showed no disease progression. Conclusions:NSS is a viable treatment option for rigorously selected patients with high-stage TSC-RAML. Although NSS causes transient renal function impairment, it provides effective tumor burden control. In stringently selected patients with high-stage disease and under long-term follow-up, NSS is associated with limited long-term renal impairment.

Objective To systematically evaluate the published models in prediction of the risk of lung infections in elderly patients with hip fracture so as to provide a guidance for medical workers in selection or development of suitable risk prediction models.Methods Relevant studies were searched from databases including CNKI,Wanfang Data,VIP,SinoMed,PubMed,Web of Science,Cochrane Library,Embase and CINAHL,from the inception to 31st January,2024.Data were extracted from the selected literature and a bias assessment tool of risk predictive model was used to evaluate the risk of bias and applicability of the included literature.Results A total of 1,035 articles were retrieved,of which seven studies involving 13 predictive models were finally included after screening.The sample sizes ranged from 305 to 2,669 cases and lung infection rates ranged from 5.40%to 20.02%.The repeatedly reported predictors included age,gender,chronic obstructive pulmonary disease,hypoproteinaemia,American Society of Anesthesiologists(ASA)Physical Status Classification and white blood cell count.In the 13 models constructed,the reported area under the curve(AUC)of subjects'job characteristics ranged from 0.667 to 0.996.Five out of seven studies had good overall applicability,but all with high risk of bias.Conclusion The predictive models for lung infections in elderly patients with hip fracture are still in the stage of development.Although the predictive models show some predictive performance,however they are still deficient,and all studies have been found with a high risk in bias.

Objective To investigate the role of matrix GLA protein(MGP)in the pathogenesis of idiopathic calcium oxalate kidney stones(ICOS),and to find potential biomarkers for early diagnosis and disease evaluation.Methods A total of 120 patients admitted to our hospital from September 2021 to September 2023 were prospectively included,of which 60 patients with ICOS were in the calculus group and 60 patients without calculus were in the control group.Serum biochemical indexes and immunohistochemical scores of the two groups were detected,urinary MGP levels were determined by ELISA,and MGP mRNA and protein expression in renal papilla tissues were detected by qPCR and Western blot.The independent risk factors of ICOS were screened by Logistic regression analysis,and the prediction model was drawn by nomogram.Results Compared with control group,urinary MGP content in calculus group was decreased[(1 805.91±244.44)pg/ml vs.(2 014.79±252.14)pg/mnl,P＜0.05).Expression of MGP mRNA and MGP protein in renal papillae decreased(0.89±0.15 vs.1.00±0.00,P=0.001)and decreased(0.87±0.18 vs.1.00±0.00,P＜0.05).MGP immunohistochemical scores of renal tissue were decreased[4(2-6)scores vs.6(4-8)scores,P＜0.001].Multivariate analysis showed that urinary calcium(OR=1.370),urinary MGP(OR=1.127),renal papilla MGP relative expression level(OR=27.532)and renal tissue MGP immunohistochemical score(OR=1.359)were independent risk factors for ICOS.Area under ROC curve of the nomogram prediction model built based on the above factors is 0.839,indicating that the model has good differentiation ability in risk prediction.Conclusion MGP is closely related to the pathogenesis of ICOS.Urinary and renal tissue MGP levels may be potential biomarkers for early diagnosis and disease assessment of ICOS.

Objective To analyze the current status of clinical trial registration of common anorectal diseases in Chinese Clinical Trial Registry(ChiCTR)and the research of TCM.Methods The ChiCTR database was retrieved to collect and organize clinical trials related to hemorrhoids,anal fissures,anal fistulas,perianal abscesses,and perianal eczema.The retrieval time was from the establishment of the database to December 10,2023.Characterization of included registration trials was analyzed.Results A total of 148 registered projects were included,75 of which were TCM-related clinical trials.Among them,134 clinical trials were pre-registered and 121 passed the ethical review.Shanghai,Jiangsu,Guangdong,Beijing and Sichuan accounted for 76.35％of the total number of registrations,and the largest number of registered projects was in Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine.The top 3 funding sources were local finance,self-funding and hospital funding.The registered projects were mainly intervention studies.114 studies used randomized methods and 34 studies were blinded.Conclusion At present,the number of ChiCTR-registered clinical trials on anorectal diseases is on an increasing trend,and the treatment of anorectal diseases with TCM has obvious characteristics.However,there are cases of irregular filling of registration content and uneven regional distribution.

Objective To investigate the role of matrix GLA protein(MGP)in the pathogenesis of idiopathic calcium oxalate kidney stones(ICOS),and to find potential biomarkers for early diagnosis and disease evaluation.Methods A total of 120 patients admitted to our hospital from September 2021 to September 2023 were prospectively included,of which 60 patients with ICOS were in the calculus group and 60 patients without calculus were in the control group.Serum biochemical indexes and immunohistochemical scores of the two groups were detected,urinary MGP levels were determined by ELISA,and MGP mRNA and protein expression in renal papilla tissues were detected by qPCR and Western blot.The independent risk factors of ICOS were screened by Logistic regression analysis,and the prediction model was drawn by nomogram.Results Compared with control group,urinary MGP content in calculus group was decreased[(1 805.91±244.44)pg/ml vs.(2 014.79±252.14)pg/mnl,P＜0.05).Expression of MGP mRNA and MGP protein in renal papillae decreased(0.89±0.15 vs.1.00±0.00,P=0.001)and decreased(0.87±0.18 vs.1.00±0.00,P＜0.05).MGP immunohistochemical scores of renal tissue were decreased[4(2-6)scores vs.6(4-8)scores,P＜0.001].Multivariate analysis showed that urinary calcium(OR=1.370),urinary MGP(OR=1.127),renal papilla MGP relative expression level(OR=27.532)and renal tissue MGP immunohistochemical score(OR=1.359)were independent risk factors for ICOS.Area under ROC curve of the nomogram prediction model built based on the above factors is 0.839,indicating that the model has good differentiation ability in risk prediction.Conclusion MGP is closely related to the pathogenesis of ICOS.Urinary and renal tissue MGP levels may be potential biomarkers for early diagnosis and disease assessment of ICOS.