To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

Objective To compare the effects of remimazolam and propofol on postoperative nausea and vomiting(PONV)after pancreatic extracorporeal shock wave lithotripsy(P-ESWL),with the aim of optimizing the anesthesia regimen for this procedure.Methods Clinical data were retrospectively collected from patients who underwent P-ESWL for pancreatic stones under general anesthesia at The First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to December 2024.A total of 307 patients were recruited,with 103 in the remimazolam group and 204 in the propofol group.Inverse probability of treatment weighting(IPTW)based on propensity scores was used to balance baseline characteristics and confounding factors between the two groups.The incidence of PONV and anesthesia recovery time were compared between the two groups.Results Before IPTW,there were statistically significant differences between the remimazolam and propofol groups in gender[male/female:51/52 vs.155/49],smoking history(27.2％vs.42.6％),intraoperative sufentanil use[25(10)μg vs.30(10)μg],remifentanil use[429.00(177)μg vs.480.50(209)μg],rocuronium use[36(6)mg vs.38(7)mg],and intraoperative dexamethasone use(62.1％vs.49.0％)(all P＜0.05).After IPTW,the baseline characteristics and confounding factors were balanced and comparable between the two groups(P＞0.05).Before IPTW,the incidence of PONV was higher in the remimazolam group than in the propofol group(24.3％vs.14.7％,P=0.039).After IPTW,the two groups did not significantly differ in the incidence of PONV(21.5％vs.17.5％,P=0.215),and the anesthesia recovery time was significantly shorter in the remimazolam group than in the propofol group[3(3)min vs.9(4)min,P＜0.001].Conclusion Compared to propofol anesthesia,remimazolam does not increase the incidence of PONV in patients undergoing P-ESWL for pancreatic stones and can effectively reduce anesthesia recovery time.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

Objective To compare the effects of remimazolam and propofol on postoperative nausea and vomiting(PONV)after pancreatic extracorporeal shock wave lithotripsy(P-ESWL),with the aim of optimizing the anesthesia regimen for this procedure.Methods Clinical data were retrospectively collected from patients who underwent P-ESWL for pancreatic stones under general anesthesia at The First Affiliated Hospital of Xi'an Jiaotong University from January 2021 to December 2024.A total of 307 patients were recruited,with 103 in the remimazolam group and 204 in the propofol group.Inverse probability of treatment weighting(IPTW)based on propensity scores was used to balance baseline characteristics and confounding factors between the two groups.The incidence of PONV and anesthesia recovery time were compared between the two groups.Results Before IPTW,there were statistically significant differences between the remimazolam and propofol groups in gender[male/female:51/52 vs.155/49],smoking history(27.2％vs.42.6％),intraoperative sufentanil use[25(10)μg vs.30(10)μg],remifentanil use[429.00(177)μg vs.480.50(209)μg],rocuronium use[36(6)mg vs.38(7)mg],and intraoperative dexamethasone use(62.1％vs.49.0％)(all P＜0.05).After IPTW,the baseline characteristics and confounding factors were balanced and comparable between the two groups(P＞0.05).Before IPTW,the incidence of PONV was higher in the remimazolam group than in the propofol group(24.3％vs.14.7％,P=0.039).After IPTW,the two groups did not significantly differ in the incidence of PONV(21.5％vs.17.5％,P=0.215),and the anesthesia recovery time was significantly shorter in the remimazolam group than in the propofol group[3(3)min vs.9(4)min,P＜0.001].Conclusion Compared to propofol anesthesia,remimazolam does not increase the incidence of PONV in patients undergoing P-ESWL for pancreatic stones and can effectively reduce anesthesia recovery time.

Objective:To investigate the association of skeletal muscle function(including muscle strength and physical performance) and insulin resistance as well as type 2 diabetes mellitus(T2DM).Methods:The retrospective study included 942 patients who visited the Department of Geriatrics at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between October 2020 and July 2024. Low skeletal muscle function was defined as either reduced muscle strength or impaired physical performance. Muscle strength was assessed by grip strength, while physical performance was evaluated using the 5-time chair stand test. The associations between muscle function, insulin resistance, and T2DM were analyzed.Results:A significant association was observed between decreased skeletal muscle function and a higher prevalence of T2DM( P=0.001). Further analysis revealed that decreased physical performance was significantly associated with increased T2DM prevalence( P<0.001), whereas reduced muscle strength showed no significant association with T2DM prevalence( P=0.331). Linear regression analysis indicated that both the homeostasis model assessment of insulin resistance(HOMA2-IR) and fasting blood glucose levels increased significantly with longer chair stand times( P<0.05). Restrictive cubic spline(RCS) analysis demonstrated a nonlinear relationship between chair-rising time and HOMA2-IR. Notably, when the cumulative chair-rising time exceed 8.1 s, HOMA2-IR increased significantly with prolonged chair stand time. Logistic regression analysis showed that compared with patients with normal physical performance, those with decreased physical performance had significantly higher odds of T2DM( OR=2.64, P<0.001) and insulin resistance( OR=2.34, P=0.002). Conclusion:Decline in physical performance is significantly positively associated with insulin resistance and the risk of T2DM. Morever, when the cumulative chair stand time exceed 8.1 s, HOMA2-IR increases progressively with further prolongation of chair stand time.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN), explore the influencing factors of the therapeutic effect and construct a nomogram model for predicting the therapeutic effect.Methods:A single retrospective study was conducted in IMN patients in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2017 to December 2022. All patients received monotherapy with RTX and were followed up for at least 12 months. RTX regimen adopted a B-cell guided regimen to achieve 0 cells/μl of peripheral blood CD19+ B cells through multiple administrations, followed by monitoring every 2?3 months and adding doses as needed to maintain this state. The complete response rate, partial response rate, and composite response rate at 6 months, 12 months and the end of follow up were analyzed. Logistic stepwise regression and R language were applied to construct a nomogram model for efficacy prediction. The receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow test were used to internally validate the nomogram model.Results:A total of 147 IMN patients were included in the study, with age of 56 (47, 65) years, 99 (67.4%) males. There were 69 (46.9%) newly treated patients, 78 (53.1%) retreatment patients. The follow-up time was 14.4 (12.0, 15.0) months. The total RTX dose was 1 800 (1 200, 2 400) mg. The composite response rates at 6 months, 12 months and the end of the follow-up were 36.7% (54/147), 59.9% (88/147) and 63.3% (93/147), respectively. The complete remission rates at 6 months, 12 months and the end of the follow-up were 6.1% (9/147), 13.6% (20/147) and 19.7% (29/147), respectively. Logistic stepwise regression analysis showed that age ≥ 65 years ( OR=0.335, 95% CI 0.135?0.833), retreatment ( OR=0.333, 95% CI 0.144?0.771), high cholesterol ( OR=0.716, 95% CI 0.577?0.888), high serum creatinine ( OR=0.978, 95% CI 0.963?0.993) and B-cell reconstruction within 6 months ( OR=0.273, 95% CI 0.115?0.645) were independent correlated factors affecting composite remission. Based on these factors, a nomogram model for predicting the therapeutic effect of RTX in IMN patients was constructed. The ROC curve indicated that the accuracy of this model in predicting composite remission was good ( AUC=0.814, 95% CI 0.744-0.883). The calibration curve showed that the predicted composite response rate had a good fit with the actual response rate (Hosmer-Lemeshow test χ2=11.917, P=0.155). Conclusions:RTX has good efficacy and safety as a monotherapy for IMN patients. The constructed nomogram prediction model has high discrimination and accuracy to predict the efficacy of RTX treatment for IMN.

Objective:Exploring the role and mechanism of gremlin-1 in lipotoxicity-mediated pancreatic β-cell dysfunction.Methods:The model of lipid toxicity-mediated pancreatic β-cell dysfunction was constructed using palmitic acid(PA) to treat mouse pancreatic β-cells(MIN6). Initially, to clarify the effects of lipotoxicity on islet β-cells, the cellular lipid deposition and changes in the levels of insulin caused by PA were detected. The effects of PA on gremlin-1 expression and its downstream signaling pathway BMPs/Smads were further investigated using qPCR and Western Blot assay. Subsequently, recombinant mouse gremlin-1 protein and BMP signaling pathway inhibitor LDN193189 were used to intervene the cells to explore the effects of gremlin-1 and its downstream signaling pathway BMPs/Smads on pancreatic islet β-cells.Results:PA could reduce pancreatic β-cell viability and insulin secretion capacity( P<0.05). Meanwhile, PA inhibited the expression and secretion of cell gremlin-1 and upregulated BMP-4 and its downstream Smad-1 and Smad-5( P<0.05). Intervention of cells with recombinant mouse gremlin-1 protein resulted in a significant elevation of insulin secretion and a concomitant decrease in the expression of key molecules in the BMP4/Smads signaling pathway( P<0.05). And inhibition of the BMP4/Smads signaling pathway ameliorated PA-induced pancreatic β-cell dysfunction. Conclusion:Gremlin-1 is involved in the regulation of lipotoxicity-mediated pancreatic islet β-cell dysfunction, and this effect may be associated with activation of BMP4/Smads signaling pathway.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.