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 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 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.

The paper reports a rare case of idiopathic multicentric Castleman's disease with nephrotic syndrome as the first presentation. The patient was a 68-year-old male, presented with edema at admission. His clinical manifestations included nephrotic syndrome, and multiple enlarged lymph nodes. Renal biopsy showed minimal change disease, and cervical lymph node biopsy showed Castleman's disease. The patient received treatment of glucocorticoid combined with tocilizumab, and then rituximab. After 14 months of follow-up, the patient achieved remission of nephrotic syndrome.

BACKGROUND:Talus cartilage injury is a common motor system disease.This type of injury will affect the patient's daily life and work ability,and may worsen the condition if left untreated.Surgical treatment is commonly used,but the selection of surgical methods and the evaluation of medium-and long-term follow-up results have always been difficult clinical problems. OBJECTIVE:To explore the influence of T1ρ technique on the range of quantitative evaluation of talus osteochondral injury on the choice of surgical method and the results of medium-and long-term follow-up. METHODS:A total of 154 patients with osteochondral injury of talus admitted to The Second Hospital of Tangshan from January 2019 to August 2022 were retrospectively selected as the study subjects.The lesion site of talus was examined by MRI before operation,and the T1ρ and T2 values of different types were compared.Different surgical methods were selected according to the different T1ρ values.Group A(n=73)was treated with microfracture surgery with T1ρ<45 ms;group B(n=81)was treated with autogenous bone and cartilage transplantation with T1ρ≥45 ms.The general clinical characteristics and curative effects of patients under different surgical methods were compared;the important factors of postoperative recurrence were analyzed by multivariate Logistic regression,and the relationship between T1ρ value and postoperative recurrence was analyzed by restricted cubic spline graph,y=1-1/(1+e-z)regression equation to build a prediction model.The stability of the model was verified by cross-checking method. RESULTS AND CONCLUSION:(1)Classification of talus osteochondral injury in 154 patients(type Ⅰ:36 cases;type Ⅱ:37 cases;type Ⅲ:40 cases;type Ⅳ:41 cases),T1ρ and T2 values of the four groups were statistically significant(P<0.05);pairwise comparison was also statistically significant(all P<0.05).(2)After treatment of 154 patients,7 cases(4.6％)had local swelling,3 cases(2.0％)had pain aggravation,and 5 cases(3.3％)had wound infection.There were 2 cases(1.3％)with poor cartilage healing.(3)After treatment,there were statistically significant differences between groups A and B in terms of American Orthopaedic Foot&Ankle Society score,visual analog scale score,plantar flexor motion range,dorsoextension motion range,subchondral bone marrow edema volume,interleukin-6,interleukin-8,C-reactive protein,procalcitonin,platelet-derived growth factor,transforming growth factor-β1,and efficacy(P<0.05).The total effective rate of group B(90％)was higher than that of group A(85％)(P<0.05).(4)Age(OR=1.589,95％CI:0.305-1.252,P=0.036),interleukin-6(OR=1.737,95％CI:0.974-5.254,P=0.049),interleukin-8(OR=1.385,95％CI:1.066-4.355,P=0.034),C-reactive protein(OR=1.957,95％CI:1.323-2.178,P=0.035),transforming growth factor-β1(OR=1.459,95％CI:0.897-2.455,P=0.038),T1-ρ(OR=1.687,95％CI:0.854-3.321,P=0.026),T2(OR=1.843,95％CI:0.657-2.454,P=0.036),complications(OR=1.719,95％CI:0.654-3.464,P=0.019),and classification of osteochondral injury of talus(OR=3.789,95％CI:1.023-5.897,P=0.028)were independent risk factors for postoperative recurrence.Microfracture surgery(OR=0.751,95％CI:0.321-1.264,P=0.012)and autogenous bone and cartilage grafting(OR=0.649,95％CI:0.246-1.356,P=0.023)were independent protective factors for recurrence after medium-and long-term follow-up.(5)When T1ρ value≤35 ms,the risk of postoperative recurrence decreased rapidly,and when T1ρ value>35 ms,the risk of postoperative recurrence increased rapidly.(6)Further stepwise regression analysis showed that these nine risk factors were most closely associated with postoperative recurrence,and the formula for postoperative recurrence was obtained.The probability of postoperative recurrence was calculated using the regression equation.When P=0.75,the maximum value of Jorden index was 77.728,indicating that the model has a better prediction effect.(7)It is indicated that the quantitative evaluation of T1ρ before operation can effectively guide the selection of surgical methods,improve the success rate of surgery and the quality of life of patients.

ObjectiveTo review the effect of response interruption and redirection intervention on vocal stereotypy in children with autism spectrum disorder (ASD). MethodsLiteratures on response interruption and redirection intervention for vocal stereotypy in children with ASD were retrieved from databases of EBSCO, PubMed, Web of Science, CNKI, and Wanfang data. The information of the literatures was extracted to conduct a scoping review. ResultsA total of 16 English literatures were included. All researches employed a single-subject time series study design. A total of 41 children with ASD were involved. Significant differences were found in levels of basic verbal functioning of children with ASD. Vocal stereotypy was characterized by both verbal and nonverbal forms. Most of the reviewed researches used experimental functional assessment to analyze the function of vocal stereotypy. In most cases, the function of vocal stereotypy was automatic reinforcement. Iwata et al.'s paradigm was dominantly adopted in performing experimental functional assessment across researches. Other related paradigms developed based on Iwata et al.'s paradigm to make operating process more concise were also used for experimental functional assessment in reviewed researches. Response disruption and redirection was often conducted in individualized setting, with a few researches conducted in special education classes. The time and frequency of interventions varied widely across subjects due to the levels of impairment in vocal stereotypy and other behaviors. According to a comparison of the effects of traditional response interruption and redirection and its morphing procedures, it was found that changing the content of the redirection task, reducing the number of redirection tasks, and varying the duration of execution did not impact the improvement of vocal stereotypy. Based on the comparisons of response interruption and redirection with matched stimuli, response cost, verbal manipulation training, and medication, it was found that both response interruption and redirection and other methods (except for medication) could reduce vocal stereotypy and promote the emergence of appropriate behaviors in children with ASD. Combining response interruption and redirection with other techniques, such as stimulus matching and response costs, yielded more favorable improvement of vocal stereotypy in children with ASD. ConclusionASD children with vocal stereotypy show different levels of functional language, and vocal stereotypy is generally characterized by both verbal and nonverbal formats. The function of vocal stereotypy is mostly automatic reinforcement. Response interruption and redirection as a behavioral intervention is mostly conducted in individualized setting, and the time and frequency of interventions depend on the levels of vocal stereotypy and other behaviors problems. Changing the content and number of redirection instructions does not significantly influence the improvement of vocal stereotypy in children with ASD. Other intervention methods such as matching stimulus and response cost are able to reduce vocal stereotypy in children with ASD, but response interruption and redirection used in conjunction with these methods show more favorable improvements. Response interruption and redirection interventions can not only reduce vocal stereotypy in children with ASD, but also increase appropriate vocalizations, task engagement and command obedience.

Objective:To investigate the graft survival rate after total parathyroidectomy (TPTX) plus forearm muscle auto-transplantation in patients with secondary hyperparathyroidism (SHPT) and evaluate the effect of graft survival status on calcium and phosphorus metabolism.Methods:It was a retrospective cohort study. The end-stage renal disease patients who were diagnosed with SHPT and underwent TPTX plus forearm muscle auto-transplantation from November 2015 to December 2018 at the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. The clinical data including serum calcium, phosphorus, intact parathyroid hormone and alkaline phosphatase preoperative and postoperative 1 week, 1 month and 6 months, and cumulative requirements of calcium carbonate and calcitriol in postoperative 1 month and 6 months were collected. The graft survival rate was summarized and the differences of serum calcium, phosphorus, and supplementation dosage of calcium and calcitriol after surgery between the graft survival group and the graft non-survival group were compared.Results:A total of 191 patients were included in the study, with 95 males (49.7%), and 172 patients of age <60 years old. There were 154 grafts surviving with a graft survival rate of 80.6%. There were no significant differences in the levels of serum calcium, phosphorus, alkaline phosphatase at 1 week, 1 month and 6 months after surgery, and cumulative dosage of calcium carbonate at 1 month and 6 months after surgery between the two groups (all P>0.05). The dose of calcitriol in the graft non-survival group was significantly higher than that in the graft survival group within 1 month after surgery [41.50 (30.00, 45.00) μg vs. 32.75 (25.50, 40.50) μg, Z=-2.307, P=0.021]. However, there was no significant difference in cumulative calcitriol supplementation between the two groups within 6 months after surgery ( P>0.05). Conclusions:The graft survival rate after TPTX plus forearm muscle auto-transplantation is high in SHPT patients. Within 6 months after surgery, there is no significant difference in serum calcium, phosphorus and cumulative supplemental doses of calcium and calcitriol between the graft survival and non-survival groups.

Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.

Objective:To analyze the clinical features of tuberculous peritonitis (TBP).Methods:The clinical data of 252 TBP patients admitted to three hospitals in Wuhu area from January 2014 to June 2020 were retrospectively analyzed, and the clinical characteristics of TBP patients of different genders and ages were compared. SPSS 26.0 software was used to analyze the data.Results:Among 252 TBP patients, 130 were males (51.6%) and 122 were females (48.4%). History of abdominal surgery, abdominal masses, reproductive disorders, genital tuberculosis, and delay in diagnosis were more common in female patients (all P<0.01); while fever, cough/sputum expectoration, intestinal tuberculosis and active tuberculosis were more common in male patients (all P<0.01). The proportion of adenosine deaminase in ascites (ADA) ≥35 U/L, strong positive tuberculin test or T-cell spot test in middle-aged and elderly patients was lower than that in young patients ( P<0.01), but there was no significant difference between different genders. Compared with young patients, middle-aged and elderly patients had a low complete response rate, a high proportion of irregular medications, a high incidence of gastrointestinal reactions, liver damage and overall adverse reactions (all P<0.05). Conclusion:Female patients with TBP have fewer symptoms of systemic tuberculosis and high rate of delay in diagnosis, and are prone to complicated with reproductive tuberculosis. In middle-aged and elderly patients with TBP, the sensitivity of ADA and tuberculosis tests is decreased, and the anti-tuberculosis therapy is less effective. The study indicates that the clinical diagnosis and treatment of TBP should be optimized based on the gender and age of patients.

BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,