1.Mechanism of resveratrol in treatment of sleep disorders in mice based on network pharmacology and experimental verification
Xi YU ; Xiaofei LYU ; Jian SUN ; Yuechun LU
International Journal of Biomedical Engineering 2025;48(2):174-181
Objective:To explore the mechanism of resveratrol in treatment of sleep disorders in mice based on network pharmacology and experimental verification.Methods:Resveratrol targets were obtained through traditional Chinese medicine systems pharmacology database and analysis platform, Swiss Target Prediction and SuperPred databases. Targets related to sleep disorders were collected from the gene expression omnibus, GeneCards, DrugBank, OMIM, CTD and MalaCards databases. Cytoscape 3.8.0 software was used to identify the core targets of resveratrol in treatment of sleep disorders via protein-protein interaction analysis. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed, and AutoDockvina software was used to conduct molecular docking between the top five core targets and resveratrol. Thirty ICR female mice were selected and divided into a control group, a model group, and low-, medium- and high-dose (10, 20, and 30 mg/kg) resveratrol groups according to the random number table method, with 6 mice in each group. Resveratrol was dissolved in 0.9% sodium chloride aqueous solution and 3% dimethyl sulfoxide. For mice in the low-, medium-, and high-dose resveratrol groups, 10, 20, and 30 mg/kg of resveratrol solution were intraperitoneally injected, respectively. The mice in the control group and the model group were intraperitoneally injected with 10 ml/kg of 0.9 % sodium chloride aqueous solution and 3 % dimethyl sulfoxide. Each group was injected once a day for 7 consecutive days. After 7 days of administration, a mouse sleep deprivation model was constructed using an improved multi platform water environment method. The spatial recognition and memory abilities of mice were tested using the Y-maze experiment, and the mRNA and protein relative expression levels of estrogen receptor 1 (ESR1) and B-cell lymphoma-2 (Bcl-2) were detected using real-time reverse transcription-PCR and Western blotting, respectively. Comparisons were made using t-test. Results:There were 47 common targets between resveratrol and sleep disorders, and the top five core targets were ESR1, Bcl-2, cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), cytochrome P450, family 2, subfamily A, polypeptide 4 (CYP3A4) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1). GO enrichment analysis revealed that resveratrol in treatment of sleep disorders was mainly related to the regulation of unsaturated fatty acid metabolic processes, secondary metabolic processes, and responses to exogenous stimuli. KEGG pathway analysis showed that resveratrol acted mainly through pathways involving chemical carcinogenic-DNA adducts, cytochrome P450 metabolism of exogenous substances and estrogen signaling pathways. Molecular docking results indicated that resveratrol had strong binding affinity with ESR1, Bcl-2, CYP1A1, CYP3A4 and CYP1B1, with binding energies of ?31.92, ?27.72, ?34.44, ?34.02 and ?31.92 kJ/mol, respectively. In vivo experiments results demonstrated that the novel arm residence time in the low-, medium- and high-dose resveratrol groups [(52±5, 55±7, and 61±9) s] was higher than that in the model group [(45±4) s] ( P<0.05 or 0.01), and the percentage of spontaneous alternation [(53±4)%, (57±5)%, and (65±7)%] was higher than that in the model group [(47±3)%] ( P<0.05 or 0.01). The relative expression levels of ESR1 mRNA (0.42±0.10, 0.49±0.11, and 0.58±0.10) were higher than those in the model group (0.29±0.06) ( P<0.05 or 0.01). The relative expression levels of Bcl-2 mRNA (0.56±0.07, 0.65±0.10, and 0.77±0.11) were higher than those in the model group (0.44±0.08) ( P<0.05 or 0.01). Similarly, the relative expression levels of ESR1 protein (0.32±0.02, 0.50±0.02, and 0.62±0.02) were higher than those in the model group (0.24±0.01) ( P<0.05 or 0.01). The relative expression levels of Bcl-2 protein (0.45±0.08, 0.69±0.06, and 0.72±0.06) were higher than those in the model group (0.17±0.04) ( P<0.05 or 0.01). Conclusions:Resveratrol exerts therapeutic effects on sleep disorders by acting on ESR1 and Bcl-2.
2.Perifornical UCN3 Neurons Regulate Overeating-Induced Weight Gain.
Shanshan LU ; Xinran ZHANG ; Wanqi CHEN ; Baofang ZHANG ; Haiyang JING ; Yunlong XU ; Fengling LI ; Chenyu JIANG ; Gaowei CHEN ; Xiaofei DENG ; Yingjie ZHU
Neuroscience Bulletin 2025;41(6):1103-1108
3.Application of blood conservation measures with different red blood cell transfusion volumes in obstetrics and their impact on postpartum outcomes
Huimin DENG ; Fengcheng XU ; Meiting LI ; Lan HU ; Xiao WANG ; Shiyu WANG ; Xiaofei YUAN ; Jun ZHENG ; Zehua DONG ; Yuanshan LU ; Shaoheng CHEN
Chinese Journal of Blood Transfusion 2025;38(5):691-698
Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL(OR=1.699)(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma(FFP), cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.
4.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
;
Drug Monitoring/methods*
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Humans
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Organ Transplantation
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Immunosuppressive Agents/administration & dosage*
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Delphi Technique
5.Characteristics of traditional Chinese medicine syndromes in patients with Chikungunya hemorrhagic fever:a cross-sectional study
Shiying LU ; Danwen ZHENG ; Xintian HONG ; Yuping LIU ; Guangzong LI ; Zhifeng HONG ; Jinghua YANG ; Yan ZHANG ; Banghan DING ; Yuntao LIU ; Yuanyuan WANG ; Xin YIN ; Jingwei SHUI ; Xiaofei FAN ; Hai LAN ; Zhongde ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(11):1531-1539
Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.
6.Clinical features and prognosis of Castleman disease in 29 children
Xiaofei ZHU ; Zhaoling WANG ; Lifeng ZHANG ; Xiaojun XU ; Meiping LU
Chinese Journal of Rheumatology 2025;29(7):583-589
Objective:To investigate the clinical features, treatment strategies, and prognosis of pediatric Castleman disease (CD), with the aim of enhancing disease recognition and improving diagnostic and therapeutic approaches.Methods:A retrospective analysis was conducted on the clinical data of 29 children diagnosed with CD at the Children′s Hospital, Zhejiang University School of Medicine, between January 2016 and January 2024. Age, sex, initial presentations, routine blood test, inflammatory indicators, coagulation function test, immunoglobulin level, histopathological examination, imaging examination, treatment and follow-ups were recorded. Patients were classified into two groups based on the presence or absence of symptoms: the symptomatic Castleman disease group (SC) and the asymptomatic Castleman disease group (AC). All patients were followed for a minimum of six months. Clinical characteristics, therapeutic regimens, and outcomes were compared between the two groups.For the measurement information, the independent samples t test was used for comparison between groups of data that conformed to normal distribution; the Mann-Whitney U test was used for comparison between groups of data that did not conform to normal distribution. The Chi-square test or Fisher′s exact probability method was used for comparison between groups of count data. Results:A total of 29 pediatric CD cases were included, comprising 15 males and 14 females. The number of patients diagnosed as unicentric Castleman disease (UCD) was 21, with the rest 8 as multicentric Castleman disease (MCD). There were 11 patients (37.9%) in the SC group and 18 patients (62.1%) in the AC group. The median age at onset was 10.0 years (interquartile range: 6.5-12.2 years). The most common initial presentation was mass ( n=20), followed by fever ( n=2), amaemia ( n=2), fever with fatigue ( n=2), rash ( n=1), abdominal pain ( n=1), and cough ( n=1). The frequently involved sites were neck ( n=8), abdominal cavity ( n=5), mediastinum ( n=3), retroperitoneum ( n=2), and one case each in the back, upper arm, and pelvis. The maximum lesion volume reached 1 040 cm 3. Compared to the AC group, the SC group had significantly lower hemoglobin levels [108.0(92.0, 123.0)g/L vs. 127.0(117.5, 139.0)g/L, Z=-2.35, P=0.019] and significantly higher levels of C-reactive protein (CRP) [38.0(3.0, 87.0)mg/L vs. 0.6(0.5, 3.8)mg/L, Z=-2.19, P=0.029], prothrombin time[12.6(11.4, 13.3)s vs. 11.3(10.5, 11.7)s, Z=-2.64, P=0.008], and fibrinogen [4.5(3.5, 5.4)g/L vs. 2.1(1.9, 2.6)g/L, Z=-3.04, P=0.002]. All patients underwent MRI/CT and ultrasonography; however, only 2 cases were diagnosed as CD by ultrasound. All patients underwent surgical excision of the mass, and diagnoses were confirmed by histopathological examination. Among the SC group, 4 patients (4/11, 36.4%) required postoperative treatment with glucocorticoids alone or in combination with immunosuppressants and biologics. The overall prognosis was favorable, with follow-up ranging from 6 months to 7 years and no reported mortality. One case, initially misdiagnosed as systemic lupus erythematosus, was later confirmed to be CD complicated with paraneoplastic pemphigus (PNP); this patient experienced recurrent fever, rash, and elevated CRP, and continued to require low-dose glucocorticoids and tacrolimus during the 4-year follow-up. Conclusion:In chileren, CD is most common in the neck and surgical resection yields favorable outcomes. Approximately 37.9% of patients present with systemic symptoms, of which about 36.4% require postoperative systemic therapy such as glucocorticosteroids. CD complicated with PNP may be misdiagnosed. Symptomatic cases are often associated with anemia, elevated CRP levels, and coagulation abnormalities. UCD pediatric patients without complications have a good prognosis and there′s no need for long-term medications after surgery. About 37.5% of MCD pediatric patients require glucocorticoids, immunosuppressants, biotherapy or chemotherapy to control symptoms in the postoperative period. Imaging modalities have limited diagnostic value, and histopathological examination remains the gold standard for diagnosis.
7.Incidence and Mortality of Colorectal Cancer in Zhejiang Cancer Registration Areas in 2021 and Trends from 2000 to 2021
Yunfeng ZHU ; Yi ZHOU ; Tianjing GAO ; Enning LU ; Xiaofei CHEN ; Zhongjie ZHU ; Weimiao WU ; Huizhang LI ; Lingbin DU ; Chunxiao JIANG ; Yanfei QIU
China Cancer 2025;34(10):783-791
[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0~74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80~84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23%,P<0.001),ASMRC showed a marginal increase(AAPC=0.78%,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.
8.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.
9.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.
10.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.

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