Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Background: Diabetes-induced testicular damage (DITD) is a common complication of diabetes. We investigated underlying mechanism of retinoblastoma-binding protein 6 (Rbbp6)-mediated brain and muscle ARNT-like 1 (Bmal1) ubiquitination in modulating ferroptosis in DITD. Methods: Spermatogenic cell apoptosis and viability were measured by flow cytometry and cell counting kit 8 (CCK-8), respectively. The impact of Rbbp6 and Bmal1 on ferroptosis was assessed by determining expression of ferroptosis markers glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), and levels of malondialdehyde (MDA), glutathione (GSH), iron, and lipid peroxidation. Co-immunoprecipitation was performed to determine the interaction between Rbbp6 and Bmal1, as well as the ubiquitination level of Bmal1. The expression levels of Rbbp6, Bmal1, Yes-associated protein 1 (YAP1), ferroptosis markers, and testicular steroidogenic enzymes were tested by Western blot. Results: Bmal1 protein expression was significantly downregulated, while Rbbp6 was upregulated in DITD mouse model and high glucose (HG)-induced GC-1 spg cells. Overexpression of Bmal1 improved testicular injury in diabetic mice, reduced 4-hydroxynonenal (4-HNE), MDA, iron levels, and increased expression levels of GPX4, SLC7A11, GSH, as well as testicular steroidogenic enzymes. Rbbp6 decreased Bmal1 level through promoting its ubiquitination. Meanwhile, Rbbp6 knockdown inhibited the ferroptosis of HG-induced GC-1 spg cells, which were abolished by silencing Bmal1. In addition, knockdown of YAP1 or treatment with ferroptosis inducer erastin blocked the above effects caused by Bmal1 overexpression. Conclusion Rbbp6-mediated Bmal1 ubiquitination suppressed YAP1 pathway, promoting ferroptosis in DITD. This study highlighted Rbbp6/Bmal1/YAP1 axis as a potential therapeutic target for mitigating DITD.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Objective:To evaluate the feasibility and efficacy of our self-designed intelligent robot-assisted reduction system for fresh subtrochanteric fractures of the femur.Methods:A retrospective cohort study was conducted to include 10 patients with fresh subtrochanteric fracture of the femur who had been admitted to Department of Orthopedic Trauma, Beijing Jishuitan Hospital from January 2024 to July 2024. There were 7 males and 3 females with an age of (45.0±14.3) years and an interval from injury to surgery of (7.9±3.7) d. All the patients were treated by minimally invasive reduction which was assisted by our self-designed intelligent robot, and internal fixation with intramedullary nails. The operation duration, intraoperative reduction duration, intraoperative blood loss, and intraoperative fluoroscopy frequency were recorded. The reduction effect was evaluated by calculating the differences between preoperative planning and postoperative CT reconstruction (i.e., the differences in femoral shaft length and in rotation angle). The hip functional recovery was assessed by Harris hip function Scoring.Results:The mean operation time was 200.0 (161.3, 217.5) min, the reduction time (83.0±35.5) min, the intraoperative blood loss (290.0±110.1) mL, and the intraoperative fluoroscopy 18.5 (9.0, 19.3) times. In all patients, the difference in femoral shaft length was (2.4±1.4) mm, and the difference in rotation angle 5.1°±3.0°. All patients were followed up for (8.2±2.0)months. All the fractures got united at the last follow-up. Their Harris hip function score was (83.3±4.1) points.Conclusion:Our self-designed intelligent robot-assisted reduction system is feasible and effective in the surgery of fresh subtrochanteric fracture of the femur, because the robot system can complete the autonomous planning of reduction approaches before surgery and assist fracture reduction under real-time monitoring with three-dimensional images, leading to fine outcomes.

Objective To systematically evaluate the incidence and influencing factors of axillary web syndrome(AWS)in postoperative breast cancer patients,and to provide evidence for reducing the incidence of axillary web syndrome.Methods A computer search was performed in China National Knowledge Infrastructure(CNKI),VIP,Wanfang,SinoMed,PubMed,Medline,Scopus,The Cochrane Library,Web of Science,Embase,searched for articles on AWS influencing factors of breast cancer published from the establishment of the database to January 6th,2025.The articles were screened according to the inclusion and exclusion criteria.Revman5.4 and Stata17.0 were used for systematic review.Results Fifteen studies involving 3979 breast cancer patients and 1 156 patients with AWS were included.The results of the Meta-analysis showed that there was significant statistical heterogeneity among the included studies(I2=97.0%,P<0.0001).Using the random effects model,the incidence of AWS was 32.2%[95%CI(0.24,0.40),P<0.0001].The influencing factors for AWS after breast cancer surgery are age,body mass index(BMI),total mastectomy,lymph node metastasis,and neoadjuvant chemotherapy.NAC),axillary lymph node dissection(ALND),and the number of harvested axillary lymph nodes.Conclusion The incidence of AWS after breast cancer surgery was high.Clinicians should give early nursing to the influencing factors,reduce the incidence of AWS and improve patients'quality of life after surgery.