1.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
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.
2.Tension hydrocele: report of 2 cases and literature review
Xun ZHAO ; Shumin WANG ; Min QIU ; Chuxiao XU ; Guoliang WANG ; Shudong ZHANG
Journal of Modern Urology 2025;30(1):69-72
[Objective] To explore the diagnosis and treatment experience of tension hydrocele. [Methods] The clinical data of 2 patients with tension hydrocele treated in our hospital were retrospectively analyzed.Relevant literature was retrieved to analyze the clinical characteristics of this disease. [Results] Case 1 was diagnosed due to swelling and pain of the left scrotum after trauma for more than one month, which worsened for one day.Physical examination showed high tension in the left scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the left testis disappeared.Emergency left scrotal exploration and hydrocelectomy were performed.There was no sign of testis torsion during the operation.Case 2 was diagnosed mainly due to hydrocele of the right testis for 1 year, which worsened for 1 week and complicated with testis distension and pain.Physical examination showed high tension in the right scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the right testis decreased.After 40ml of fluid was extracted under ultrasound monitoring, the blood flow signal in the right testis recovered.Hydrocelectomy was performed the next day.During the follow-up of 8 months, there was no recurrence of hydrocele.A search of domestic and foreign literature showed that there were no reports in domestic literature, while a total of 11 cases were reported in foreign literature. [Conclusion] Tension hydrocele of the testis is a rare emergency of the scrotum.Surgery or decompression should be performed as soon as possible to restore testicular blood supply, and hydrocelectomy should be performed simultaneously or in stages to prevent recurrence.
3.Internal tension relieving technique assisted anterior cruciate ligament reconstruction to promote ligamentization of Achilles tendon grafts in small ear pigs in southern Yunnan province
Bohan XIONG ; Guoliang WANG ; Yang YU ; Wenqiang XUE ; Hong YU ; Jinrui LIU ; Zhaohui RUAN ; Yajuan LI ; Haolong LIU ; Kaiyan DONG ; Dan LONG ; Zhao CHEN
Chinese Journal of Tissue Engineering Research 2025;29(4):713-720
BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).
4.Relationship between metabolic score for insulin resistance and overactive bladder in the US population based on NHANES data from 2005 to 2018
Guoliang XU ; Feiyang GAO ; Xihao WANG ; Jiangtao ZHU ; Wei LIN ; Pengyue LIU ; Yongjun YAN
Journal of Modern Urology 2025;30(5):416-423
Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population,so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018,a cross-sectional design was employed,and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations,subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001),and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females,participants younger than 55 years,and non-diabetic individuals (P<0.05). Furthermore,smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB,with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study,based on the NHANES 2005-2018 database,found a linear positive correlation between METS-IR and OAB.
5.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
6.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
7.Clinical Observation of Modified Huanglian Wendantang in Treatment of Cardiovascular Risk Factors in Patients with Metabolic Syndrome Under Guidance of Treating Disease before Its Onset
Yi HAN ; Yubo HAN ; Guoliang ZOU ; Ruinan WANG ; Chunli YAO ; Xinyu DONG ; Li LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):142-149
ObjectiveTo observe the clinical effect of modified Huanglian Wendantang on cardiovascular risk factors in patients with metabolic syndrome under the guidance of treating disease before its onset. MethodsA total of 82 patients with metabolic syndrome treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2023 to July 2024 were selected and allocated into an observation group (41 cases) and a control group (41 cases) by the random number table method. The control group received routine treatment, and the observation group was treated with modified Huanglian Wendantang on the basis of routine treatment. Both groups were treated for 8 weeks. The therapeutic effects on TCM symptoms after treatment in the two groups were evaluated. The levels of obesity degree indicators, blood pressure indicators, glucose and lipid metabolism indicators, inflammatory factors, and vascular endothelial function indicators before and after treatment in the two groups were measured, and the treatment safety was evaluated. ResultsAfter treatment, the total response rate of TCM symptoms in the observation group was 97.56% (40/41), which was higher than that (87.80%, 36/41) in the control group (χ2=5.205, P<0.05). After treatment, both groups showed declines (P<0.05) in systolic blood pressure (SBD), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), fasting blood glucose, 2-hour postprandial blood glucose (2 h PG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), leptin (LEP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1), and inducible nitric oxide synthase (iNOS). Moreover, the declines in the observation group were more obvious than those in the control group (P<0.05, P<0.01). After treatment, both groups showed elevated levels of high density lipoprotein cholesterol (HDL-C), adiponectin (ADP), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS) (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.01). ConclusionUnder the guidance of the thought of treating disease before its onset, modified Huanglian Wendantang was used to treat patients with metabolic syndrome. The decoction improved the clinical efficacy by ameliorating IR to improve insulin sensitivity, reducing inflammation, and protecting the vascular endothelial function. It inhibits cardiovascular risk factors without inducing adverse reactions, being worthy of clinical application and promotion.
8.Robot-assisted laparoscopic inferior vena cava segmental resection for renal tumor with tumor thrombus invading the vascular wall
Shuai LIU ; Zhuo LIU ; Yunhe GUAN ; Guoliang WANG ; Xiaojun TIAN ; Hongxian ZHANG ; Lei LIU ; Lulin MA ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):796-802
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.
9.Clinicopathological and prognostic differences between clear cell and non-clear cell renal cell carcinoma with venous tumor thrombus
Boda GUO ; Min LU ; Guoliang WANG ; Hongxian ZHANG ; Lei LIU ; Xiaofei HOU ; Lei ZHAO ; Xiaojun TIAN ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):644-649
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.
10.Clinicopathological features and survival analysis of TFE3-rearranged renal cell carcinoma with venous tumor thrombus
Zhanyi ZHANG ; Min LU ; Yuehao SUN ; Jinghan DONG ; Xiaofei HOU ; Chunlei XIAO ; Guoliang WANG ; Xiaojun TIAN ; Lulin MA ; Hongxian ZHANG ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):650-661
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.

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