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Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.
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Objective:To evaluate the feasibility of using positive anti-M-type phospholipase A 2 receptor(PLA 2R)antibody detection as a surrogate for renal biopsy in the diagnosis of idiopathic membranous nephropathy(IMN)in elderly Chinese. Methods:From June 2021 to March 2022, clinicopathological data of ninety-six elderly patients(≥60 years old)with positive anti-PLA 2R antibody detection(ELISA≥14 RU/ml), complete renal pathology records, and the exclusion of secondary disease and diabetes mellitus were collected from the Department of Nephrology, The First Affiliated Hospital of Zhengzhou University.Patients were divided into high eGFR group(≥60 ml·min -1·1.73 m -2)and low eGFR group(<60 ml·min -1·1.73 m -2), and the data were analyzed retrospectively. Results:Of the 96 patients, 95(99.0%)had IMN(1 in stage Ⅰ, 59 in stage Ⅱ, 34 in stage Ⅲ, and 1 in stage Ⅳ), and 1(1.0%)had atypical membranous nephropathy(AMN).For the IMN patients, 81(85.3%)had high eGFR and most IMN patients(66.7%)were in stage Ⅱ, with 10(12.3%)showing additional pathological findings, including mild mesangial proliferative IgA nephropathy(2 cases)and subacute tubulointerstitial nephropathy(2 cases).There were 14 patients(14.7%)with low eGFR, and most of them(57.1%)had stage Ⅲ IMN, with 10(71.4%)showing additional pathological findings.This percentage was higher than that in the high eGFR group( χ2=21.642, P<0.05).The most common additional pathological findings were acute tubular injury(4 cases)and ischemic kidney injury(2 cases). Conclusions:Positive anti-PLA 2R antibody detection is highly predictive of IMN in elderly Chinese patients, but it often co-exists with other pathological entities.The advantages of renal biopsy in detecting other pathological conditions and the risks associated with the procedure should be evaluated.
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Objective:To explore the mediating role of alexithymia in the relationship between trait anger and aggressive behavior among male violent prisoners.Methods:A sample of 268 male violent prisoners completed self-report measures of the trait anger scale (TAS), Toronto alexithymia scale-20 (TAS-20) and the Chinese college students' version of Buss-Perry aggression questionnaire. SPSS 23.0 software and Mplus 8.0 software were used to test the mediating effect.Results:The total scores of trait anger, aggressive behavior and alexithymia were (17.75±4.93), (52.15±10.61)and (70.90±19.40), respectively. Pearson correlation analysis showed that trait anger was both significantly positively correlated with aggressive behavior ( r=0.67, P<0.01) and alexithymia ( r=0.40, P<0.01), and there was also a significantly positive correlation between alexithymia and aggressive behavior ( r=0.55, P<0.01). Multivariate hierarchical regression analysis showed that trait anger directly predicted aggressive behavior ( β=0.67, P<0.01) after controlling the influence of alcohol addiction. Emotional recognition disorder played a partially mediating role in the relationship between trait anger and aggressive behavior ( β=0.18, 95% CI=0.11-0.27). Conclusion:Trait anger not only directly affects male violent prisoners aggressive behavior, but also indirectly affects male violent prisoners aggressive behavior through emotional recognition disorder.
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Objective:To compare the prognosis of hemodialysis (HD) and peritoneal dialysis (PD) in end-stage renal disease (ESRD) patients without diabetes mellitus and identify related influencing factors.Methods:Patients who started hemodialysis with an arteriovenous graft or fistula or PD in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to February 1,2019 were included. They were followed up until May 1, 2019. The patients were divided into HD group and PD group according to the initial dialysis modality. Kaplan-Meier method was used to obtain survival curves, the Cox regression model was used to evaluate influence factors for survival rates, and the inverse probability of treatment weighting (IPTW) was used to eliminate influence of the confounders in the groups.Results:There were 371 patients with maintenance dialysis enrolled in this study, including 113 cases (30.5%) in HD group and 258 cases (69.5%) in PD group. At baseline, the scores of standard mean difference ( SMD) in age, body mass index (BMI), combined with cerebrovascular disease, Charlson comorbidity index (CCI), blood potassium, plasma albumin and hemoglobin between the two groups were greater than 0.1. The score of SMD decreased after IPTW, and the most data were less than 0.1, which meant that the balance had been reached between the two groups. The Kaplan-Meier survival curve showed that the cumulative survival rates had no significant difference for all-cause death before using IPTW between the two groups (Log-rank χ2=0.094, P=0.759). After adjusting for confounders with IPTW, the Kaplan-Meier survival curve showed that the cumulative survival rates still had no significant difference for all-cause death between the two groups (Log-rank χ2=2.090, P=0.150). Univariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus for all-cause death (PD/HD, HR=1.171, 95% CI 0.426-3.223, P=0.760). Multivariate Cox regression analysis showed that there was no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus (PD/HD, HR=1.460, 95% CI 0.515-4.144, P=0.477), and high plasma albumin ( HR=0.893, 95% CI 0.813-0.981, P=0.019) was an independent protective factor for survival in ESRD patients without diabetes mellitus. There was still no significant difference between HD and PD on survival rates in ESRD patients without diabetes mellitus after using IPTW (PD/HD, HR=1.842, 95% CI 0.514-6.604, P=0.348). Conclusion:The difference of cumulative survival rates between HD and PD is not significant in ESRD patients without diabetes mellitus.
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Objective To investigate the incidence situation of metabolic syndrome (MS) in patients with continuous ambulatory peritoneal dialysis (CAPD),and analyze the correlation between MS and prognosis of patients.Methods The patients who received peritoneal dialysis from June 1,2002 to April 30,2018 and followed up regularly were divided into MS group and non-MS group according to the diagnostic criteria of MS.Follow-up was until July 31,2018.The differences of clinical data,metabolic indexes and clinical outcomes between the two groups were compared.The survival rates of the two groups were compared by Kaplan-Meier survival curve,and the risk factors of all-cause death and cardiovascular disease (CVD) death were analyzed by Cox regression analysis.Results A total of 516 patients with CAPD were enrolled in this study,including 340 males (65.9%)and 176 females (34.1%).Their age was (47.29± 12.20) years.The median follow-up time was 20 (9,39) months.According to the diagnostic criteria of MS,the patients were divided into MS group (210 cases,40.7%) and non-MS group (306 cases,59.3%).At baseline,there was no significant difference in age,educational background,duration of peritoneal dialysis,smoking history and drinking history between the two groups (P > 0.05),but the patients in MS group were more exposed to high glucose peritoneal dialysate (P < 0.05).The body mass index (BMI),blood phosphorus,blood glucose,blood potassium,triglyceride,cholesterol and systolic blood pressure in MS group were significantly higher than those in non-MS group (all P < 0.05),and HDL-C level was significantly lower in MS group than in non-MS group (P < 0.05).There were no significant differences in other indicators between the two groups (P > 0.05).Kaplan-Meier survival curve showed that the cumulative survival rate in MS group was significantly lower than that in non-MS group,and the difference was statistically significant (Log-rank x2=14.87,P < 0.001).If CVD death was taken as the end event,the cumulative survival rate in the non-MS group was significantly higher than that in the MS group (Log-rank x2=14.49,P < 0.001).Multivariate Cox regression analysis showed that MS and high 4 h dialysate creatinine/serum creatinine ratio (4hD/Pcr) were independent risk factor for all-cause death (HR=1.982,95%CI 1.240-3.168,P=0.004;HR=3.855,95%CI 1.306-11.381,P=0.015) and CVD death (HR=2.499,95%CI 1.444-4.324,P=0.001;HR=5.799,95% CI 1.658-20.278,P=0.006) in patients with CAPD.Conclusion The prevalence of MS in patients with CAPD is high,and MS and high 4hD/Pcr are independent risk factor for all-cause and CVD death in CAPD patients.They can be used as valuable indicators to predict the treatment outcomes and long-term prognosis of patients with CAPD.
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Objective To investigate the association of red cell distribution width (RDW) with all-cause and cardiovascular disease (CVD)-related mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).Methods A retrospective analysis was performed on 207 patients who initiated CAPD for more than 3 months between July 2005 and March 2016 in the First Hospital Affiliated to Zhengzhou University.Baseline data on demographic,clinical and biochemical variables as well as comorbidities were obtained;medications and clinic outcomes were recorded.According to receiver operator characteristic curve (ROC) analysis,patients were divided into high RDW (RDW > 15.1%) and low RDW (RDW≤ 15.1%) groups.The data of two groups were compared and Spearman's correlation analysis was used to explore the association of RDW with clinical and biochemical parameters.Survival curves were calculated using Kaplan-Meier method.Cox regression model was employed to analyze risk factors of all-cause and CVD-related mortality.Results In this study,207 CAPD patients were enrolled.The overall median survival time was 80 months.And the median survival time of high RDW group (68 patients) and low RDW group (139 patients) were 59 months and 96 months,respectively.There were statistical differences in diastole pressure,hemoglobin,hematocrit,serum albumin,intact parathyroid hormone (iPTH),eGFR,cholesterol,lipoprotein a,4-hour dialysate-to-plasma ratio for creatinine (4hD/Pcr),total Ccr (P < 0.05,respectively);the two groups also varied in the proportion of chronic obstructive pulmonary disease,cardiovascular disease and hyperlipidemia,as well as in the use of iron supplements,angiotensin-converting enzyme (ACE) inhibitors or angiotensin Ⅱ receptor blockers (ARB),and beta-receptor blockers (P<0.05,respectively).Cardiovascular event was a leading cause of mortality.Kaplan-Meier survival curves showed that the high RDW group had higher all-cause and CVD-related mortality compared with the low RDW group (P < 0.01).The 1-year,3-year,and 5-year patient survivals of the high RDW and low RDW group were 87.97% vs 97.01%,58.02% vs 81.53%,and 41.62% vs 67.96%,respectively,demonstrating significant differences (P=0.001).Multivariate Cox regression analysis showed that high RDW was independent risk factor for all-cause mortality (HR=1.212,95%CI:1.007-1.458,P=0.042) and CVD-related mortality (HR=1.697,95% CI:1.030-2.795,P=0.038).Conclusion RDW is associated with mortality risks in CAPD patients and can be stratified as a valuable indicator for the risk of death.
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Objective To investigate whether the JAK2/STAT3 signaling pathway is involved in the epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells in uremic peritoneal dialysis (PD) rats.Methods A total of 48 male Sprague-Dawley (SD) rats were randomly separated into six groups:normal control group (NC group,n=8),sham group (n=8),uremic group (n=8),PD group (n=8),S3I-201 control group (n=8) and S3I-201 group (n=8).Uremic model generated by 5/6 nephrectomy surgery in rats was established.The rats of PD group,S3I-201 control group and S3I-201 group received daily infusion of 4.25% glucose-based peritoneal dialysate fluid (3 ml/100 g) from PD catheters for 28 days.Rats of S3I-201 group were injected with STAT3 inhibitor S3I-201 (2.5 mg/kg) solution from the catheters every other day;the same dose of the solvent of S3I-201 was simultaneously given to S3I-201 control group rats.After PD for 28 days,peritoneal function,pathologic changes,and microvessel density (MVD) were evaluated.Creatinine,urea nitrogen and interleukin-6 (IL-6) concentration in blood and dialysate,and protein and mRNA levels of phospho-JAK2 (p-JAK2),phospho-STAT3 (p-STAT3),E-cadherin,alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) in peritoneum were determined.Results Uremia and peritoneal dialysate could aggravate the peritoneal function and elevate peritoneal thickness and MVD.They could also increased the concentration of IL-6 in blood and dialysate and the expression levels of α-SMA,VEGF,p-JAK2 and p-STAT3 in peritoneum,while lowering E-cadherin expression in peritoneum.These manifestations were even more remarkable in PD group compared to those in uremic group.There was no statistical difference between the S3I-201 control group and the PD group as regards all the index (all P > 0.05).Compared with the S3I-201 control group,the rats treated with S3I-201 showed better peritoneal function.S3I-201 could reduce peritoneal thickness (P<0.05),MVD (P<0.05),the concentration of IL-6 in blood and dialysate,the mRNA and protein expression of α-SMA,VEGF,p-JAK2 and p-STAT3 (all P < 0.05),while enhance the mRNA and protein expression of E-cadherin (all P < 0.05).Conclusions After STAT3 is inhibited,the peritoneal thickness,MVD and IL-6 concentration in PD rats are decreased,and EMT is also inhibited,while peritoneal function is improved.The JAK2/STAT3 signaling pathway may thus be involved in the process of EMT of peritoneum in uremic peritoneal dialysis rats by regulating the expression of IL-6.
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Objective To investigate the role of STAT3 transcription factor in IL-6 inducing epithelial mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs).Methods HPMCs were cultured in vitro and grouped.(1) According to the stimulation time with 50 μg/L IL-6,HPMCs were divided into 24,48,72 h groups.(2) HPMCs were grouped 50,100 μg/L according to IL-6 concentration.(3) HPMCs were respectively divided into control group,IL-6 group,empty vector group,empty vector+IL-6 group,virus infecting group and virus infecting+IL-6 group,as lenti-virus vector mediating RNA interference targeting STAT3 was applied.The mRNA expressions of E-cadherin,α-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) were detected by real time PCR;their protein expressions and the phosphorylation of JAK2 and STAT3 were detected by Western blotting;the expressions and distribution of E-cadherin and α-SMA were observed by immunofluorescence.Results Compared with those in control group,the expression of E-cadherin decreased remarkably (P < 0.05),while the expressions of VEGF and α-SMA and the ratio of phosphorylated (p)-JAK2/JAK2 and p-STAT3/STAT3 increased significantly in IL-6 concentration groups and stimulation time groups (all P < 0.05),which had been dose and time dependent.Compared with empty vector+IL-6 group,virus infecting+IL-6 group had decreased expressions of VEGF and α-SMA,while increased expressions of E-cadherin (all P < 0.05).Conclusions IL-6 can promote VEGF and α-SMA gene expression and prevent E-cadherin gene expression by STAT3,which involves in EMT of peritoneum fibrosis.While STAT3 gene is knocked-down,EMT is inhibited in HPMCs.
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Objective To investigate the role of STAT3 transcription factor in IL-6 inducing epithelial mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs).Methods HPMCs were cultured in vitro and grouped.(1) According to the stimulation time with 50 μg/L IL-6,HPMCs were divided into 24,48,72 h groups.(2) HPMCs were grouped 50,100 μg/L according to IL-6 concentration.(3) HPMCs were respectively divided into control group,IL-6 group,empty vector group,empty vector+IL-6 group,virus infecting group and virus infecting+IL-6 group,as lenti-virus vector mediating RNA interference targeting STAT3 was applied.The mRNA expressions of E-cadherin,α-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) were detected by real time PCR;their protein expressions and the phosphorylation of JAK2 and STAT3 were detected by Western blotting;the expressions and distribution of E-cadherin and α-SMA were observed by immunofluorescence.Results Compared with those in control group,the expression of E-cadherin decreased remarkably (P < 0.05),while the expressions of VEGF and α-SMA and the ratio of phosphorylated (p)-JAK2/JAK2 and p-STAT3/STAT3 increased significantly in IL-6 concentration groups and stimulation time groups (all P < 0.05),which had been dose and time dependent.Compared with empty vector+IL-6 group,virus infecting+IL-6 group had decreased expressions of VEGF and α-SMA,while increased expressions of E-cadherin (all P < 0.05).Conclusions IL-6 can promote VEGF and α-SMA gene expression and prevent E-cadherin gene expression by STAT3,which involves in EMT of peritoneum fibrosis.While STAT3 gene is knocked-down,EMT is inhibited in HPMCs.