To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged

OBJECTIVES: To investigate the active ingredients in Hedyotis diffusa-Scutellaria barbata D. Don and the main biological processes and signaling pathways mediating their inhibitory effect on primary hepatocellular carcinoma (HCC). METHODS: The core intersecting genes of HCC and the two drugs were screened from TCMSP, Uniport, Genecards, and String databases using Cytoscape software, and GO and KEGG enrichment analyses of the intersecting genes were conducted. Molecular docking between the active ingredients of the drugs and the core genes was carried out using Pubcham, RCSB and Autoduckto to identify the active ingredients with the highest binding energy, whose inhibitory effect on HepG2 cells was verifies using CCK-8 assay, flow cytometry and Western blotting. RESULTS: TP53 and ESR1 were identified as the core genes of HCC and the two drugs. GO and KEGG analyses showed that the two genes were mainly involved in regulation of apoptotic signaling pathway, cell population proliferation, methane raft, and protein kinase activity, and participated in the signaling pathways of apoptosis, proteoglycans in cancer, PI3K Akt signaling pathway, and hepatitis B. Molecular docking studies showed that the active ingredients of the drugs could be docked with TP53 and ESR1 genes under natural conditions, and ursolic acid had the highest binding energy to ESR1 (-4.98 kcal/mol). The results of CCK-8 assay, flow cytometry and Western blotting all demonstrated significant inhibitory effect of ursolic acid on HepG2 cells. CONCLUSIONS The inhibitory effect of Hedyotis diffusa-scutellariae barbatae on HCC is mediated by multiple active ingredients in the two drugs.
Humans ; Molecular Docking Simulation ; Liver Neoplasms/drug therapy* ; Hep G2 Cells ; Network Pharmacology ; Carcinoma, Hepatocellular/drug therapy* ; Hedyotis/chemistry* ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Apoptosis/drug effects* ; Estrogen Receptor alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Objective To observe the performance and safety of self-developed real-time three-dimensional intracardiac echocardiography(ICE)system(system).Methods The self-developed system was constructed using disposable sterile real-time three-dimensional ICE catheter(catheter)and multifunctional cart-mounted digital ultrasound imaging host(ultrasound host).The diameter of catheter was 10F,with effective length of 90 cm and two-dimensional array transducer array(840 elements)integrated at tip.The ultrasound host was connected to the catheter through matching connector.The performance of this system was evaluated with self-made experimental equipment and standard phantom,and live animal experiment was performed to observe its safety and imaging quality.Results The maximum imaging depth of this system was ≥60 mm.Its axial resolution was ≤1 mm and lateral resolution was ≤1 mm within the depth of 40 mm,the horizontal and vertical geometric position accuracy errors were ≤10％and ≤5％,respectively,while the image geometric distortion was ≤10％,and the measurement volume error was ≤30％.The catheter was successfully inserted into right atrium of pig through femoral vein under ultrasound guidance,smoothly passing through the vascular pathway without any bending or jamming with good controllability.The cardiac images of this system were clear,which completely displayed cardiac chamber structures,and the image resolution met diagnostic requirement.No injury related to interventional procedures was found in laboratory tests nor anatomical results.Conclusion The self-developed ICE system was stable and safe,and initial results showed it could meet clinical application expectations.

Objective:To investigate the clinical and pathological characteristics, prognostic factors, and treatment outcomes of bladder adenocarcinoma.Methods:The data of 177 bladder adenocarcinoma patients treated at Renji Hospital, Shanghai Jiaotong University School of Medicine from January 2003 to December 2023, and 2 687 bladder adenocarcinoma patients from the SEER database (2000—2021) were reviewed retrospectively. The clinicopathological and prognostic characteristics were compared between the two cohorts. Patients with urachal adenocarcinoma or primary bladder adenocarcinoma were included, while metastatic bladder adenocarcinoma from other sites and urothelial carcinoma with glandular components were excluded. The Chi-square test was used for comparison of categorical data, and propensity score matching (1∶1) was applied to match baseline data between the Renji and SEER cohorts. Kaplan-Meier survival curves were generated, and log-rank tests were used for comparisons. Univariate and multivariate Cox regression analyses were performed using the survival R package, with P-values calculated via Wald tests. Results:The proportion of localized bladder adenocarcinoma was significantly higher in the Renji cohort than in the SEER cohort [61.0% (108/177) vs. 19.4% (521/2 687), P<0.001], and mucinous adenocarcinoma was more common in Renji cohort [33.3% (59/177) vs. 22.6% (607/2 687), P<0.001]. After matching for baseline factors, including SEER stage and pathological grade, survival analysis revealed that the Renji cohort patients had slightly better survival compared to the SEER cohort [median survival: 55.4 (24.1, 196.2) months vs. 39.2 (13.6, 137.4)months, P=0.033]. Multivariate Cox analysis identified SEER stage [Renji cohort: HR=3.83 (95% CI 1.62-9.07), P=0.002; SEER cohort: HR=3.67 (95% CI 3.13-4.31), P<0.001] and pathological grade [Renji cohort: HR = 2.76 (95% CI 1.54-4.95), P=0.001; SEER cohort: HR=1.46 (95% CI 1.29-1.65), P<0.001] as independent prognostic factors. In the Renji cohort, no significant differences were observed in the median progression-free survival [40.1 (19.5, 91.6) months vs. 40.9 (12.8, not reached)months, P=0.976] and overall survival [79.3 (37.1, 195.8) months vs. 53.9 (16.4, 129.5)months, P=0.374] between patients receiving adjuvant chemotherapy and those not receiving it. However, among patients with lymph node-positive bladder adenocarcinoma, adjuvant chemotherapy significantly improved both progression-free survival [40.1 (38.2, 75.4) months vs. 12.2 (3.1, 12.2)months, P=0.004] and overall survival [68.2 (46.2, 84.5)months vs. 28.1 (4.3, 28.3)months, P=0.006]. Conclusions:Bladder adenocarcinoma is rare and associated with poor prognosis. Compared to the SEER cohort, Renji cohort patients had more localized disease, with no significant differences in other features. SEER stage and pathological grade were independent prognostic factors in both cohorts. Lymph node-positive bladder adenocarcinoma patients in the Renji cohort benefited significantly from adjuvant chemotherapy.

Objective:To evaluate the safety and oncological outcomes of robot-assisted laparoscopic inferior vena cava(IVC)segmental resection in renal tumor with IVC tumor thrombus(IVCTT).Methods:Clinical data from renal tumor patients undergoing robot-assisted laparoscopic IVC segmental resection at Peking University Third Hospital from Jan.2021 to Feb.2025 were retrospectively analyzed.Data collection included baseline demographics,tumor characteristics,perioperative parameters,and follow-up outcomes.Surgical records and pathological reports were retrieved from the electronic medical record system.Continuous variables were presented as median(P25,P75),and categorical variables as frequency(percentage).Results:Forty-four patients were enrolled.The cohort comprised 31 malesand 13 females,with a median age of 62(55,68)years.Right-sided tumors were observed in 39 cases and left-sided in 5 cases.Median tumor diameter was 8.1(6.1,10.1)cm.Mayo classifications included grade Ⅱ(n=37),Ⅲ(n=6),and Ⅳ(n=1).Neoadjuvant therapy was administered to 23 patients.Seventeen patients were complicated by IVC bland thrombus.Median operative time was 224.0(167.3,303.8)min,with intraoperative blood loss of 500.0(300.0,850.0)mL.Transfusion was administered to 19 patients,with a median blood transfusion of 800.0(400.0,1 200.0)mL.Postoperative complica-tions occurred in 25 cases(56.8％),classified as Clavien-Dindo grade Ⅰ(n=8)and grade Ⅱ(n=17).Procedure-specific complications included deep vein thrombosis(n=6),transfusion-requiring ane-mia(n=5),lower extremity edema(n=2),and pulmonary embolism(n=2),with no procedure-related mortality.Median postoperative serum creatinine was 116.0(86.5,157.5)μmnol/L.Pathological examination identified clear cell renal cell carcinoma as the predominant subtype,observed in 34 cases(77.3％).Pathological staging revealed T3b(n=12),T3c(n=29),and T4(n=3)disease,with nodal involvement(N1)in 8 cases and distant metastasis(M1)in 17.At a median follow-up of 10 months(range:1-49 months),cancer-specific mortality occurred in 3 patients,while 1 succumbed to other causes.Disease progression included pulmonary metastasis(n=5),hepatic metastasis(n=4),and local recurrence(n=4).Adjuvant therapy regimens comprised targeted-immunotherapy combina-tions(n=9)and targeted monotherapy(n=18).Conclusion:Robot-assisted laparoscopic I VC seg-mental resection achieves precise thrombus removal with confirmed short-term efficacy in renal tumor with IVCTT,though vigilance against vascular complications remains critical.

Objective:To compare the clinicopathological characteristics and prognostic outcomes between patients with clear cell renal cell carcinoma(ccRCC)and non-clear cell renal cell carcinoma(nccRCC)accompanied by venous tumor thrombus.Methods:A retrospective analysis was conducted on clinical and pathological data from patients with RCC and venous tumor thrombus treated in the Depart-ment of Urology at Peking University Third Hospital between January 2014 and February 2024.Patients were stratified into two groups based on pathological type:ccRCC and nccRCC.Comparisons of baseline characteristics,intraoperative situation,and prognosis between the two groups were performed using t-tests,Mann-Whitney U tests,chi-square tests,and Log-rank tests.Survival curves were generated using the Kaplan-Meier method.Results:A total of 437 patients were included,with a median age of 58 years,including 317 males and 120 females.The cohort comprised 366 cases of ccRCC and 71 cases of nccRCC.The non-clear cell group included 38 cases(53.5％)of papillary renal cell carcinoma,2 cases(2.8％)of chromophobe renal cell carcinoma,11 cases(15.5％)of unclassified renal cell carcinoma,19 cases(26.8％)of molecularly defined renal cell carcinoma,and 1 case(1.4％)of collecting duct carcinoma.Compared with the clear cell renal carcinoma group,patients in the non-clear cell carcinoma group demonstrated a younger age at diagnosis(59 years vs.55 years,P=0.010),larger tumor size(8.4 cm vs.9.5 cm,P=0.025),higher rates of lymph node metastasis(56.8％vs.70.6％,P=0.034),more advanced tumor thrombus(P＜0.001)and pathological grading(P=0.010),longer surgical duration(272 minutes vs.289 minutes,P=0.023),and shorter overall survival(80 months vs.35 months,P＜0.001).Multivariate Cox analysis indicated that histologic type,distant metastasis,tumor thrombus grading,and sarcomatoid/rhabdoid differentiation were prognostic factors in the renal cell carcinoma patients with venous tumor thrombus.No significant differences were observed between the two groups in terms of gender,body mass index,tumor laterality,distant metastasis,sarcomatoid or rhabdoid differentiation,American Society of Anesthesiologists(ASA)score,surgical approach,conversion to open surgery,blood loss,or transfusion of red blood cells and plasma.Conclusion:Compared with pa-tients with clear cell renal carcinoma and venous tumor thrombus,those with non-clear cell carcinoma and venous tumor thrombus exhibit earlier onset,more aggressive disease progression,and poorer prognosis.

Objective:To review the clinicopathological features of TFE3-rearranged renal cell carcino-ma(TFE3-RCC)with venous tumor thrombus(VT)(TFE3-VT),to explore treatment strategies and to prognostic characteristics,and to provide diagnostic and therapeutic references for TFE3-VT patients.Methods:Patients who underwent surgery at Department of Urology,Peking University Third Hospital from January 2013 to January 2024 were enrolled,including three cohorts:Pathologically confirmed TFE3-VT patients,TFE3-RCC patients without VT(TFE3-non-VT),and non-TFE3-rearranged renal cell carcinoma patients with VT(non-TFE3-VT).Clinical history,imaging data,pathological data,and follow-up records were collected.Primary and secondary endpoints were progression-free survival(PFS)and overall survival(OS),respectively.(1)Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients.Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test;non-normally distributed variables were expressed as M(P25,P75)and analyzed with Mann-Whitney U test;categorical variables were described as frequency and percentage[n(％)]and compared by x2 test or Fisher's exact test.(2)Clinical history,radiological presenta-tions,surgical data,and histopathological features of the TFE3-VT patients were comprehensively charac-terized.(3)Survival analysis was performed for the TFE3-VT patients.Follow-up data of the TFE3-VT patients were described in detail,and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients.When compared with the TFE3-non-VT counterparts,Kaplan-Meier method was used to generate PFS and OS curves among:(1)the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ;(2)TFE3-VT versus TFE3-non-VT cohorts;(3)stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients.Intergroup survival differences were statistically evaluated using Log-rank tests.For comparisons with the non-TFE3-VT patients,a 1∶1 propensity score matching(PSM)was implemented to balance baseline characteristics between the two cohorts.Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups,with Log-rank tests employed to determine statistical significance of survival disparities.All statistical analyses were conducted with R software(v 4.2.3),and two-tailed P＜0.05 was considered statistically significant.Results:The study included 45 TFE3-RCC patients:13 TFE3-VT and 32 TFE3-non-VT cases.Additionally,523 non-TFE3-VT patients were enrolled.Among the 13 TFE3-VT patients,9 were female(69.2％)and 4 male(30.8％),with a mean age of(37.9±14.4)years,mean BMI of(22.2±3.5)kg/m2,median age-adjusted Charlson comorbidity index(aCCI)of 1.0(0.0,1.0),and preoperative creatinine level of(75.3±15.9)μmol/L;tumors were located in the left kidney in 7 patients(53.8％)and right kidney in 6(46.2％);preoperative distant metastasis(M1 stage)was present in 6 patients(46.2％),while 7(53.8％)showed no metastasis;VT distribution by Mayo level comprised 7 cases(53.8％)at level 0,1 case each at levels Ⅰ and Ⅳ(7.7％respectively),and 2 cases each at levels Ⅱ and Ⅲ(15.4％respectively);surgical approaches comprised open surgery(n=2,15.4％),laparoscopic surgery(n=6,46.1％),and robot-assisted laparoscopic surgery(n=5,38.5％);mean operative time was(273±79)min,and intraoperative blood loss was(722±570)mL;mean maximum tumor diameter was(10.8±2.4)cm.All the 13 patients underwent TFE3 protein immunohistochemistry(IHC)staining,with 7 confirmed by fluorescence in situ hybridization(FISH).Tumor recurrence or metastasis occurred in 11 patients(84.6％),and 9(69.2％)patients died during follow-up.Median PFS was 4 months(1 year PFS rate:31％),and median OS was 13 months(1 year OS rate:54％).Survival analysis of 45 TFE3-RCC pa-tients revealed statistically significant differences in PFS and OS across all the clinical stages(P＜0.001).The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients(P＜0.001),with persistent significance in stage Ⅲ subgroup analysis(P＜0.05).After PSM,TFE3-VT pa-tients showed significantly inferior PFS compared with non-TFE3-VT(P=0.01),though no significant difference was shown between the OS curves(P=0.11).Conclusion:TFE3-VT predominantly occurs in young females with frequent preoperative metastases.Strongly-positive staining of TFE3 protein in IHC stai-ning and red-green split signals in FISH tests are reliable diagnostic markers.TFE3-VT patients exhibit in-ferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.