1.A cross-sectional questionnaire survey on the prevalence and risk factors of 4 major functional gastrointestinal disorders among children in Shanghai
Yanfei WANG ; Zhanyong YAO ; Yuan XIAO ; Xinqiong WANG ; Yiqiu HUANG ; Chundi XU ; Yi YU
Chinese Journal of Pediatrics 2025;63(7):747-753
Objective:To investigate the prevalence and risk factors of the 4 most common functional gastrointestinal disorders (FGID) among school-aged children in Shanghai.Methods:A cross-sectional questionnaire survey was conducted from January to December 2019. Using stratified cluster sampling, 26 097 students in grades 1-12 from Huangpu and Jiading District, Shanghai were enrolled. The questionnaire of pediatric gastrointestinal symptoms-Rome Ⅳ (QPGS-Ⅳ) and the pediatric quality of life inventory (PedsQL) were used to assess the prevalence and health-related quality of life (HRQoL) of functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain-not otherwise specified (FAP-NOS), and functional constipation (FC). Multivariate Logistic regression analysis was performed to identify correlations between sociodemographic factors, lifestyle habits, comorbidities and 4 major FGID. A trend chi-square test was used to explore the relationship between HRQoL scores and FGID prevalence.Results:A total of 26 097 valid participants (26 097/27 036, 96.5%) were included in the study, with the age of (10.8±3.1) years and 12 441 cases (47.7%) were female. The prevalence of FC was found to be the highest (5 537 cases, 21.2%), followed by IBS (797 cases, 3.1%), FAP-NOS (267 cases, 1.0%) and FD (218 cases, 0.8%). Multivariate Logistic regression analysis revealed the following findings: junior high school (FD: OR=1.88 (95% CI 1.35-2.61); IBS: OR=1.42 (95% CI 1.18-1.71); FAP-NOS: OR=1.39 (95% CI 1.02-1.90)), senior high school (FD: OR=2.67 (95% CI 1.84-3.86);IBS: OR=2.36 (95% CI 1.93-2.89) ;FAP-NOS: OR=2.20 (95% CI 1.56-3.11)) and frequent respiratory infections (FD: OR=2.15 (95% CI 1.45-3.18); IBS: OR=2.59 (95% CI 2.12-3.16); FAP-NOS: OR=1.49 (95% CI 1.00-2.21)) were common risk factors for FD, IBS and FAP-NOS. Allergic symptoms (FD: OR=2.21 (95% CI 1.56-3.14); IBS: OR=2.30 (95% CI 1.04-1.51); FAP-NOS: OR=2.54 (95% CI 1.85-3.50); FC: OR=1.09 (95% CI 1.01-1.17)) was a common risk factor for FD, IBS, FAP-NOS and FC. Family history of allergy was a risk factor for IBS ( OR=1.41 (95% CI 1.20-1.65)) and FAP-NOS ( OR=1.33 (95% CI 1.01-1.74)). Female exhibited increased risks for FD ( OR=1.49 (95% CI 1.13-1.96)), IBS ( OR=1.50 (95% CI 1.30-1.74)) and FC ( OR=1.10 (95% CI 1.03-1.17)). The presence of dietary bias was associated with of IBS ( OR=1.46 (95% CI 1.26-1.69)) and FC ( OR=1.26 (95% CI 1.19-1.34)); late bedtime ( OR=1.32 (95% CI 1.06-1.64)) and allergen exposure ( OR=1.25 (95% CI 1.04-1.51)) were risk factors for IBS. Insufficient sleep ( OR=1.11 (95% CI 1.02-1.21)), insufficient outdoor time ( OR=1.20 (95% CI 1.01-1.43)) and severe lack of outdoor time ( OR=1.48 (95% CI 1.23-1.76)) were significant risk factors for FC. Pet ownership ( OR=1.39 (95% CI 1.07-1.81)) was a risk factor for FAP-NOS. HRQoL scores were significantly lower in children with FD, IBS, or FAP-NOS compared to non-FGID peers (all P<0.05). χ2 trend test analysis showed that the Pearson correlation coefficients between the prevalence of FD, IBS, FAP-NOS, FC and HRQoL scores were -0.93, -0.93, -0.97 and -0.84, respectively. Conclusions:The prevalence of FGID among school-aged children in Shanghai varies by sub-type. FC was the most prevalence. Junior and senior high school, female sex, allergic symptoms and frequent respiratory infections were major risk factors. Meanwhile, dietary bias, late bedtime, insufficient outdoor time and pet ownership were associated with specific subtypes. The HRQoL is significantly reduced in children with FD, IBS and FAP-NOS.
2.Clinical application of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors
Xuefeng FU ; Lei ZENG ; Yuan JIANG ; Meiyan WANG ; Bingjing JIANG ; Yanfei ZHANG
China Modern Doctor 2025;63(13):19-22
Objective To evaluate the application value of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors.Methods A retrospective analysis was performed on 123 patients with head and facial skin masses admitted to Affiliated Jinhua Hospital,Zhejiang University School of Medicine from June 2019 to December 2023.Patients were divided into two groups according to their wishes.Patients in group A underwent preoperative dermoscopy combined with intraoperative rapid frozen section examination,and patients in group B underwent preoperative skin biopsy combined with intraoperative rapid frozen section examination.The diagnostic accuracy of two methods was compared.Results There were 81 patients in group A,including 39 basal cell carcinoma,25 squamous cell carcinoma,8 solar keratosis,5 seborrheic keratosis and 4 verrucous nevus.There were 42 patients in group B,including 25 basal cell carcinoma,13 squamous cell carcinoma and 4 solar keratosis.Both groups of patients successfully completed the operation,postoperative follow-up 6 months no recurrence.The accuracy of dermoscopy in the diagnosis of head and facial skin masses was 91.36%,and the accuracy of skin biopsy was 100%.There was no statistical significance between them(x2=2.407,P=0.121).Conclusion In surgical treatment of head and facial skin tumors,the diagnostic accuracy of preoperative dermoscopy combined with intraoperative rapid frozen section examination is high,and it is worthy of clinical promotion.
3.Preoperative MRI for predicting the invasiveness of pancreatic solid pseudopapillary neoplasm
Yanfei LIN ; Yanxia JIN ; Jiamei YAO ; Yuan JI ; Shouping DAI ; Mengsu ZENG ; Mingliang WANG
Chinese Journal of General Surgery 2025;40(3):201-206
Objective:To explore the value of magnetic resonance examination in distinguishing invasive and non-invasive pancreatic solid pseudopapillary neoplasms (SPN).Methods:The clinical and MRI data of 167 patients with SPN who underwent surgery and were pathologically diagnosed at Zhongshan Hospital ,Fudan University from Oct 2013 to Oct 2023 were retrospectively analyzed.Results:There was no statistically significant difference between invasive and non-invasive SPN in terms of age, gender, clinical symptoms, laboratory tests, location, growth pattern, tumor size, relationship with the pancreas, bleeding, and pancreatic duct dilation ( P>0.05). However, there were statistically significant differences between the two groups in terms of tumor morphology, margins, capsule, cystic solid ratio, pancreatic atrophy, enhancement pattern, and enhancement features ( P<0.05). The area under the ROC curve for the combined indicators (tumor morphology, margins, capsule, cystic solid ratio, and pancreatic atrophy) was 0.679 (95% CI: 0.594-0.764), with a sensitivity of 73.7% and specificity of 70.9%. Conclusion:Magnetic resonance examination is helpful in distinguishing invasive and non-invasive pancreatic solid pseudopapillary neoplasms.
4.Molecular Mechanisms of Huangjing Zanyu Capsule in Treating Oligoasthenospermia:A Study Based on AMPK-Mediated Mitophagy
Yuan GAO ; Yiyang GUO ; Mohan WU ; Yanfei ZHENG
Journal of Sichuan University (Medical Sciences) 2025;56(1):74-82
Objective To investigate the molecular mechanism of Huangjing Zanyu Capsule(HJZY),a new class-Ⅲ traditional Chinese medicine for the treatment of male infertility developed by Wang Qi,an academician of the Chinese Academy of Engineering,based on AMPK-mediated mitophagy in the treatment of oligoasthenospermia.Methods Acrolein(ACR)was used to treat GC-2spd(ts)mouse spermatocytes to establish a cell model of oligoasthenospermia.The optimal ACR concentration and exposure time for subsequent modeling were determined by CCK8 cell viability assay.After successful modeling,the cells were cultured in complete medium containing different concentrations of HJZY.Then,cell viability was assessed by CCK8 assay after 24 hours,and the subsequent treatment concentration was determined based on the cell viability.After the GC-2spd cells adhered to the wall,they were divided into a normal control(NC)group,a modeling group,and an ACR+HJZY treatment group.The effect of HJZY on mitophagy was observed by confocal fluorescence microscopy.The three groups of cells were transfected with siRNA-NC and siRNA-AMPK,respectively,and divided into six groups,including siRNA-NC+control,siRNA-NC+ACR,siRNA-NC+ACR+HJZY,siRNA-AMPK+control,siRNA-AMPK+ACR,and siRNA-AMPK+ACR+HJZY groups.Western blot was performed to validate the regulatory effect of HJZY on mitophagy-related proteins,such as p-AMPK,LC3B,P62,PINK1,Parkin,TBK1,and ULK1,which were all proteins mediated by AMPK.Results Through the cell viability assay,34 μmol/L was selected as the the modeling concentration of ACR,and 20 minutes was selected as the modeling time The treatment concentration of HJZY was 160 μmol/L.Confocal fluorescence microscopy showed that HJZY had,to a certain degree,a positive regulatory effect on the mitochondrial membrane potential of damaged spermatogenic cells.The mitochondrial membrane potential of the model group decreased significantly compared with that of the NC group.After exposure to treatment,the cell membrane potential of the ACR+HJZY treatment group increased compared with that of the model group,and the difference was statistically significant(P<0.05).Western blot results showed that the expression levels of p-AMPK/AMPK and PINK1 proteins in the siRNA-NC+ACR group were significantly lower than those in the siRNA-NC+control group(P<0.001).The level of Parkin protein in the siRNA-NC+ACR group was lower than that in the siRNA-NC+control group,but the difference was not statistically significant.After the administration of HJZY,the levels of these 3 proteins increased,and those in the siRNA-NC+ACR+HJZY group were higher than those in the siRNA-NC+ACR group(P<0.001).The expression levels of LC3B,P62,TBK1,and ULK1 proteins in the siRNA-NC+ACR group were higher than those in the siRNA-NC+control group(P<0.01),and those in the siRNA-NC+ACR+HJZY group were lower than those in the siRNA-NC+ACR group(P<0.05).After transfection with the gene-silencing siRNA-AMPK,the expression levels of p-AMPK/AMPK,PINK1,and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-AMPK+control group(P<0.01).After the administration of HJZY,there was no significant difference in the levels of these three proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.The expression level of LC3B protein in the siRNA-AMPK+ACR+HJZY group was still lower than that in the siRNA-AMPK+ACR group(P<0.01).There was no significant difference in the levels of P62,TBK1,and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-AMPK+ACR group.Compared with the siRNA-NC+control group,the siRNA-AMPK+control group showed significantly decreased expression levels of p-AMPK/AMPK,ULK1,and TBK1 proteins(P<0.001),decreased expression of PINK1 protein(P<0.05),and increased expression of P62 protein(P<0.001).Compared with the siRNA-NC+ACR group,the siRNA-AMPK+ACR group showed decreased expression of TBK1 protein(P<0.001),decreased expression of LC3B protein(P<0.01),and decreased expression of ULK1 protein(P<0.05).The expression levels of PINK1 and Parkin proteins in the siRNA-AMPK+ACR group were lower than those in the siRNA-NC+ACR group,but the difference was not statistically significant.Compared with the siRNA-NC+ACR+HJZY group,the siRNA-AMPK+ACR+HJZY group showed decreased expression of p-AMPK/AMPK,PINK1,and Parkin proteins(P<0.05),decreased expression of LC3B protein(P<0.01),and increased expression of P62 protein(P<0.001).There was no significant difference in the levels of TBK1 and ULK1 proteins between the siRNA-AMPK+ACR+HJZY group and the siRNA-NC+ACR+HJZY group.Conclusion HJZY may exert its therapeutic effect on oligoasthenospermia by regulating AMPK-mediated mitophagy.
5.Preoperative MRI for predicting the invasiveness of pancreatic solid pseudopapillary neoplasm
Yanfei LIN ; Yanxia JIN ; Jiamei YAO ; Yuan JI ; Shouping DAI ; Mengsu ZENG ; Mingliang WANG
Chinese Journal of General Surgery 2025;40(3):201-206
Objective:To explore the value of magnetic resonance examination in distinguishing invasive and non-invasive pancreatic solid pseudopapillary neoplasms (SPN).Methods:The clinical and MRI data of 167 patients with SPN who underwent surgery and were pathologically diagnosed at Zhongshan Hospital ,Fudan University from Oct 2013 to Oct 2023 were retrospectively analyzed.Results:There was no statistically significant difference between invasive and non-invasive SPN in terms of age, gender, clinical symptoms, laboratory tests, location, growth pattern, tumor size, relationship with the pancreas, bleeding, and pancreatic duct dilation ( P>0.05). However, there were statistically significant differences between the two groups in terms of tumor morphology, margins, capsule, cystic solid ratio, pancreatic atrophy, enhancement pattern, and enhancement features ( P<0.05). The area under the ROC curve for the combined indicators (tumor morphology, margins, capsule, cystic solid ratio, and pancreatic atrophy) was 0.679 (95% CI: 0.594-0.764), with a sensitivity of 73.7% and specificity of 70.9%. Conclusion:Magnetic resonance examination is helpful in distinguishing invasive and non-invasive pancreatic solid pseudopapillary neoplasms.
6.Clinical application of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors
Xuefeng FU ; Lei ZENG ; Yuan JIANG ; Meiyan WANG ; Bingjing JIANG ; Yanfei ZHANG
China Modern Doctor 2025;63(13):19-22
Objective To evaluate the application value of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors.Methods A retrospective analysis was performed on 123 patients with head and facial skin masses admitted to Affiliated Jinhua Hospital,Zhejiang University School of Medicine from June 2019 to December 2023.Patients were divided into two groups according to their wishes.Patients in group A underwent preoperative dermoscopy combined with intraoperative rapid frozen section examination,and patients in group B underwent preoperative skin biopsy combined with intraoperative rapid frozen section examination.The diagnostic accuracy of two methods was compared.Results There were 81 patients in group A,including 39 basal cell carcinoma,25 squamous cell carcinoma,8 solar keratosis,5 seborrheic keratosis and 4 verrucous nevus.There were 42 patients in group B,including 25 basal cell carcinoma,13 squamous cell carcinoma and 4 solar keratosis.Both groups of patients successfully completed the operation,postoperative follow-up 6 months no recurrence.The accuracy of dermoscopy in the diagnosis of head and facial skin masses was 91.36%,and the accuracy of skin biopsy was 100%.There was no statistical significance between them(x2=2.407,P=0.121).Conclusion In surgical treatment of head and facial skin tumors,the diagnostic accuracy of preoperative dermoscopy combined with intraoperative rapid frozen section examination is high,and it is worthy of clinical promotion.
7.A cross-sectional questionnaire survey on the prevalence and risk factors of 4 major functional gastrointestinal disorders among children in Shanghai
Yanfei WANG ; Zhanyong YAO ; Yuan XIAO ; Xinqiong WANG ; Yiqiu HUANG ; Chundi XU ; Yi YU
Chinese Journal of Pediatrics 2025;63(7):747-753
Objective:To investigate the prevalence and risk factors of the 4 most common functional gastrointestinal disorders (FGID) among school-aged children in Shanghai.Methods:A cross-sectional questionnaire survey was conducted from January to December 2019. Using stratified cluster sampling, 26 097 students in grades 1-12 from Huangpu and Jiading District, Shanghai were enrolled. The questionnaire of pediatric gastrointestinal symptoms-Rome Ⅳ (QPGS-Ⅳ) and the pediatric quality of life inventory (PedsQL) were used to assess the prevalence and health-related quality of life (HRQoL) of functional dyspepsia (FD), irritable bowel syndrome (IBS), functional abdominal pain-not otherwise specified (FAP-NOS), and functional constipation (FC). Multivariate Logistic regression analysis was performed to identify correlations between sociodemographic factors, lifestyle habits, comorbidities and 4 major FGID. A trend chi-square test was used to explore the relationship between HRQoL scores and FGID prevalence.Results:A total of 26 097 valid participants (26 097/27 036, 96.5%) were included in the study, with the age of (10.8±3.1) years and 12 441 cases (47.7%) were female. The prevalence of FC was found to be the highest (5 537 cases, 21.2%), followed by IBS (797 cases, 3.1%), FAP-NOS (267 cases, 1.0%) and FD (218 cases, 0.8%). Multivariate Logistic regression analysis revealed the following findings: junior high school (FD: OR=1.88 (95% CI 1.35-2.61); IBS: OR=1.42 (95% CI 1.18-1.71); FAP-NOS: OR=1.39 (95% CI 1.02-1.90)), senior high school (FD: OR=2.67 (95% CI 1.84-3.86);IBS: OR=2.36 (95% CI 1.93-2.89) ;FAP-NOS: OR=2.20 (95% CI 1.56-3.11)) and frequent respiratory infections (FD: OR=2.15 (95% CI 1.45-3.18); IBS: OR=2.59 (95% CI 2.12-3.16); FAP-NOS: OR=1.49 (95% CI 1.00-2.21)) were common risk factors for FD, IBS and FAP-NOS. Allergic symptoms (FD: OR=2.21 (95% CI 1.56-3.14); IBS: OR=2.30 (95% CI 1.04-1.51); FAP-NOS: OR=2.54 (95% CI 1.85-3.50); FC: OR=1.09 (95% CI 1.01-1.17)) was a common risk factor for FD, IBS, FAP-NOS and FC. Family history of allergy was a risk factor for IBS ( OR=1.41 (95% CI 1.20-1.65)) and FAP-NOS ( OR=1.33 (95% CI 1.01-1.74)). Female exhibited increased risks for FD ( OR=1.49 (95% CI 1.13-1.96)), IBS ( OR=1.50 (95% CI 1.30-1.74)) and FC ( OR=1.10 (95% CI 1.03-1.17)). The presence of dietary bias was associated with of IBS ( OR=1.46 (95% CI 1.26-1.69)) and FC ( OR=1.26 (95% CI 1.19-1.34)); late bedtime ( OR=1.32 (95% CI 1.06-1.64)) and allergen exposure ( OR=1.25 (95% CI 1.04-1.51)) were risk factors for IBS. Insufficient sleep ( OR=1.11 (95% CI 1.02-1.21)), insufficient outdoor time ( OR=1.20 (95% CI 1.01-1.43)) and severe lack of outdoor time ( OR=1.48 (95% CI 1.23-1.76)) were significant risk factors for FC. Pet ownership ( OR=1.39 (95% CI 1.07-1.81)) was a risk factor for FAP-NOS. HRQoL scores were significantly lower in children with FD, IBS, or FAP-NOS compared to non-FGID peers (all P<0.05). χ2 trend test analysis showed that the Pearson correlation coefficients between the prevalence of FD, IBS, FAP-NOS, FC and HRQoL scores were -0.93, -0.93, -0.97 and -0.84, respectively. Conclusions:The prevalence of FGID among school-aged children in Shanghai varies by sub-type. FC was the most prevalence. Junior and senior high school, female sex, allergic symptoms and frequent respiratory infections were major risk factors. Meanwhile, dietary bias, late bedtime, insufficient outdoor time and pet ownership were associated with specific subtypes. The HRQoL is significantly reduced in children with FD, IBS and FAP-NOS.
8.Prognostic Values of caIMR for the Prognosis of Patients with STEMI after Primary PCI
Yixuan WU ; Lei CHEN ; Yanfei REN ; Yulin YANG ; Yuan LU
Journal of Medical Biomechanics 2024;39(2):346-354
Objective To explore the prognostic value of the coronary angiography-derived index of microcirculatory resistance(caIMR)for major adverse cardiovascular events(MACE)in patients with acute ST-segment elevation myocardial infarction(STEMI)after primary percutaneous coronary intervention(PCI).Methods Between September 2019 and March 2022,541 patients diagnosed with STEMI at the Affiliated Hospital of Xuzhou Medical University were enrolled.The caIMR was calculated using the FlashAngio system(Suzhou Rainmed Medical Technology Co.,Ltd.).The patients were divided into MACE and non-MACE groups according to the occurrence of MACE during hospitalization or follow-up,with MACE defined as all-cause mortality,heart failure readmission,and unplanned revascularization.COX regression analysis,receiver operating characteristic(ROC)curves,and Kaplan-Meier survival curves were used to evaluate the prognostic value of caIMR for STEMI patients after primary PCI.Results During the 1-year follow-up,61 patients(11.28%)experienced MACE.The patients in the MACE group had higher caIMR values than those in the non-MACE group.Multivariate COX analysis showed that caIMR was an independent risk factor for MACE.ROC curve analysis showed that caIMR predicted MACE with an area under the curve of 0.688,and the optimal cutoff value was 25.3 U.caIMR significantly increased the discriminant and reclassification indexes when added to a model with clinical risk factors.The patients were further divided into a low caIMR group(caIMR<25 U,n=377)and a high caIMR group(caIMR ≥25 U,n=164).Kaplan-Meier curve showed that patients with caIMR≥25 U had a worse prognosis.Conclusions caIMR is an independent risk factor for poor prognosis after PCI in patients with STEMI,and patients with caIMR≥25 U had a worse prognosis.
9.Clinical features of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma: a multi-center real-world retrospective study
Yunze XU ; Wen KONG ; Ming CAO ; Guangxi SUN ; Jinge ZHAO ; Songyang LIU ; Zhiling ZHANG ; Liru HE ; Xiaoqun YANG ; Haizhou ZHANG ; Lieyu XU ; Yanfei YU ; Hang WANG ; Honggang QI ; Tianyuan XU ; Bo YANG ; Yichu YUAN ; Dongning CHEN ; Dengqiang LIN ; Fangjian ZHOU ; Qiang WEI ; Wei XUE ; Xin MA ; Pei DONG ; Hao ZENG ; Jin ZHANG
Chinese Journal of Urology 2024;45(3):161-167
Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.
10.Study on the Protective Effect of mitoTEMPO on Podocyte Injury in Rat Models with Chronic Kidney Disease by Modulating Mitochondrial Autophagy
Ruoshuang WANG ; Yanfei LENG ; Feiyuan YUAN
Journal of Modern Laboratory Medicine 2024;39(5):22-29
Objective To investigate the effect of mitochondria-targeted 2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino(mitoTEMPO)on podocyte injury in rat models with chronic kidney disease(CKD)and its related molecular mechanisms.Methods A total of 18 healthy SD rats were randomly divided into control group,model group(CKD group),and mitoTEMPO group,with 6 rats in each group.Renal function was measured by a fully automated biochemical analyzer,and hematoxylin eosin staining was used to detect renal pathological structure.Immunohistochemical staining was used to detect the expression of desmin and podocin in the renal muscle.Transmission electron microscopy was used to detect the ultrastructure of foot cells.Immunofluorescence co staining was used to detect mitochondrial autophagy in podocytes.Real time fluorescence quantitative PCR was used to detect the expression of renal inflammatory factors.Protein immunoblotting was used to detect the expression of Nod-like receptor protein 3(NLRP3)inflammatory bodies,autophagy,and Parkin/PTEN induced putative kinase 1(PINK1)pathway related proteins.Results Compared with the control group,the levels of 24h urinary protein(84.89±8.98 mg/24h vs 5.79±1.39 mg/24h),serum creatinine(Scr)(75.10±10.46 μmol/L vs 38.57±4.89 μmol/L)and blood urea nitrogen(BUN)(8.96±1.07 mmol/L vs 2.73±0.43mmol/L)in CKD group were increased,with significant differences(t=21.322,7.749,13.233,all P<0.001).The CKD group showed an increase in glomerular volume,mesangial proliferation,and extensive infiltration of inflammatory cells in rats.The foot processes of podocytes in the CKD group were fused,the basement membrane was thickened,and mitochondrial cristae were fractured and vacuolated.Compared with the control group,the positive area of desmin in the CKD group was increased,while the positive area of podocin was decreased,with significant differences(t=9.903,7.651,all P<0.001).Meanwhile,p62 and desmin were co-localized in the CKD group.In addition,the protein expressions of LC3 Ⅱ/Ⅰ,PINK1 and Parkin in the CKD group were decreased(t=16.984,15.105,11.390),while the expression of IL-1β,TNF-α,NLRP3,cleaved caspase-1 and p62 protein was increased(t=5.700~21.571),and the differences were significant(all P<0.001),respectively.Compared with CKD group,the levels of 24h urinary protein,Scr and BUN in mitoTEMPO group were decreased,and the differences were significant(t=12.508,4.712,7.338,all P<).001).Renal pathological damage and podocyte condition of mitoTEMPO group were improved,while mitoTEMPO group showed decreased desmin-positive area and increased podocin-positive area(t=6.649,7.686,all P<0.001),and colocalization of LC3 and COX Ⅳ was observed in mitoTEMPO group.In addition,the protein expressions ofLC3 Ⅱ/Ⅰ,PINK1 and Parkin in mitoTEMPO group were increased(t=15.481,20.469,5.801),while IL-1 β,TNF-α,NLRP3,cleaved caspase-l,and p62 protein were decreased(t=3.477~9.681),and the differences were significant(all P<0.001),respectively.Conclusion The mitoTEMPO can be protective against CKD podocyte injury,and the mechanism may be related to the activation of PINK1/parkin pathway-mediated mitochondrial autophagy to inhibit NLRP3 inflammasome.

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