As a pattern recognition receptor, Toll-like receptor 4 (TLR4) is crucial for the development and progression of acute kidney injury (AKI). This study aims to explore whether the deubiquitinase Usp9x influences the TLR4/NF-B pathway to cause sepsis-induced acute kidney injury (S-AKI). The model of AKI was established in Sprague-Dawley rats using the cecal ligation and puncture (CLP) method, while renal tubular epithelial cell NRK-52E was stimulated with lipopolysaccharide (LPS) in vitro. All plasmids were transfected into NRK-52E cells according to the indicated group. The deubiquitinase of TLR4 was predicted by the online prediction software Ubibrowser. Subsequently, Western blot and Pearson correlation analysis identified Usp9x protein as a potential candidate. Co-IP analysis verified the interaction between TLR4 and Usp9x. Further research revealed that overexpression of Usp9x inhibited degradation of TLR4 protein by downregulating its ubiquitination modification levels. Both in vivo and in vitro experiments observed that interference with Usp9x effectively alleviated the inflammatory response and apoptosis of renal tubular epithelial cells (RTECs) induced by CLP or LPS, whereas overexpression of TLR4 reversed this situation. Transfection with sh-Usp9x in NRK-52E cells suppressed the expression of proteins associated with the TLR4/NF-κB pathway induced by LPS. Moreover, the overexpression of TLR4 reversed the effect of sh-Usp9x transfection. Therefore, the deubiquitinase Usp9x interacts with TLR4, leading to the upregulation of its expression through deubiquitination modification, and the activation of the TLR4/NF-κB signaling pathway, thereby promoting inflammation and apoptosis in renal tubular epithelial cells and contributing to sepsis-induced acute kidney injury.

Objective This study aims to evaluate the efficacy of a novel surgical procedure for pyriform sinus fistulas in children via the external cervical approach through the hypopharynx.Methods A retrospective analysis was conducted on 71 pediatric patients with pyriform sinus fistula (PSF) who underwent treatment at the Department of Otolaryngology Head and Neck Surgery, Shanghai Children's Hospital, from 2012 July to 2022 July. Surgical treatment of PSF was performed via the external cervical approach through the hypopharynx, with dye instilled through the internal opening to serve as a guide for tract identification.Results All the internal orifices were found in the pyriform sinus by direct laryngoscopy in all 71 patients under general anesthesia. Two patients had a postoperative temporary hoarseness that resolved after 3 months. The other patients had no complications such as parapharyngeal abscess and incision infection. All patients were followed up for 23 months-70 months, and no recurrence was found.Conclusion The novel surgical procedure of PSF performed via the hypopharynx has advantages such as a short operation path, quick recovery, fewer complications, and a low recurrence rate. This method is a better choice for managing recurrence cases after repeated cauterization endoscopic surgeries, as well as for patients with visible cervical surgical scars or masses.

Objective To assess the efficacy and safety of three treatment modalities (rituximab targeted B-cell therapy, calcium-phosphate inhibitor in conjunction with low-dose corticosteroids, and full-dose corticosteroids combined with cyclophosphamide) for patients at intermediate or high risk of idiopathic membranous nephropathy (IMN) and to analyze the factors impacting the remission rates of IMN. Methods A retrospective cohort study was conducted to analyze patients diagnosed with IMN in our nephrology department via renal biopsy, identifying a total of 148 patients at intermediate or high risk. These patients were categorized into three treatment groups: a RTX group with 60 patients receiving rituximab, a CNI group with 42 patients receiving calcineurin inhibitors, and a CTX group with 46 patients received cyclophosphamide. Baseline measurements of 24-hour urine protein, serum albumin, blood creatinine, uric acid, estimated glomerular filtration rate (eGFR), and serum anti-phospholipase A2 receptor antibody levels were recorded at the onset of the follow-up. Subsequently, changes in 24-hour urine protein, eGFR, remission rates, and occurrence of adverse events among the three patient groups were compared at 6, 12, and 18 months post-treatment. Moreover, COX regression analysis was employed to ascertain factors influencing the remission rate of IMN. Results At the outset of the follow-up period, no significant difference existed in baseline characteristics such as gender, age, 24-hour urine protein quantification, serum albumin, serum creatinine, uric acid, eGFR, serum anti-PLA2R antibody levels, body mass index (BMI), and systolic blood pressure among the patients, indicating the comparability of three groups. After 6 months, there were no notable changes in 24-hour urine protein quantification and eGFR among the three groups; however, remission rates in the RTX and CTX groups were lower than those in the CNI group. By the 12-month mark, 24-hour urine protein quantification in the RTX group significantly decreased compared to the CTX group, with overall remission rates showing no significant differences among the three groups. By the 18-month milestone, 24-hour urine protein quantification in the RTX group remained notably lower than that in the CTX group, with significantly higher eGFR levels. Additionally, the CTX group exhibited lower 24-hour urine protein quantification compared to the CNI group, with both RTX and CTX groups displaying higher remission rates than the CNI group. Predominant adverse reactions in the RTX group included infusion reactions and infections, whereas the CNI group were associated with metabolic syndrome and elevated serum creatinine, and the CTX group primarily experienced hepatic dysfunction. Multifactorial COX regression analysis revealed an association between baseline anti-PLA2R antibodies and remission rates of IMN (HR=1.162, 95% CI 1.078-1.249). Conclusion RTX therapy for IMN exhibits a gradual onset of action, boasting a superior disease remission rate at 18 months in comparison to CNI. It demonstrates a similarity to CTX in this aspect and offers prolonged maintenance of remission. Conversely, CNI demonstrates a rapid onset of action but poses a risk of exacerbating renal impairment in patients. Notably, elevated levels of serum anti-PLA2R antibodies emerge as an independent risk factor influencing remission in IMN.

BACKGROUND AND AIMS:The prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion(MaVI)is poor, and the treatment is limited. This study aims to explore the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC), combined with lenvatinib and programmed cell death-1(PD-1) inhibitor in the first-line treatment of HCC with MaVI.METHODS:From July 2020 to February 2022, we retrospectively analyzed consecutive patients with HCC with MaVI who received hepatic arterial infusion FOLFOX(oxaliplatin, 5-fluorouracil, and leucovorin)combined with lenvatinib and PD-1 inhibitor. The efficacy was evaluated by RECIST 1.1. Kaplan-Meier was used to explore the overall survival and progression-free survival (PFS), and the COX regression model was used to analyze the risk factors of PFS. Adverse events (AEs) were evaluated according to CTCAE5.0.RESULTS:Thirty-two patients with HCC complicated with MaVI were recruited from the Second Affiliated Hospital of Nanchang University. Among the patients treated with HAIC combined with lenvatinib and PD-1 inhibitor, ten patients (31.25%) got partial response, eighteen patients (56.25%) maintained stable disease and four patients (12.50%) suffered progressive disease during follow-up; and objective response rate was 31.25%, and disease control rate was 87.5%. The median PFS was 179 days. Univariate and multivariate Cox analysis showed that the extrahepatic metastases and Child-Pugh score were independent prognostic factors of PFS. Twenty-two (68.75%) patients suffered adverse reactions. The main AEs were elevated transaminase (46.87%), thrombocytopenia (40.63%), hypoalbuminemia (28.13%), nausea and vomiting (21.88%), leukopenia (18.76%), abdominal pain (15.63%), hypertension (15.63%) and fever (15.63%). There were seven cases (21.88%) that had grade 3 or above AEs; Among them, two cases with elevated transaminase (6.25%), leukopenia, thrombocytopenia, nausea and vomiting, abdominal pain, and diarrhea occurred in one case respectively. Moreover, no treatment-related death was observed.CONCLUSIONS:Hepatic arterial infusion of FOLFOX combined with lenvatinib and PD-1 inhibitor as the first-line treatment for HCC complicated with MaVI is effective, and adverse reactions are tolerable.

Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of 'universal' immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a beta(2)-microglobulin super-enhancer (B2M-SE) that is responsive to interferon-gamma is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy.

Objective:This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).Methods:This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University.Results:The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936-0.984) and 0.9326 (95% CI: 0.8747-0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model.Conclusion:The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.

Thrombotic microangiopathy is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury. The pathological features include vascular damage that is manifested by arteriolar and capillary thrombosis with characteristic abnormalities in the endothelium and vessel wall. Thrombocytopenia is one of the common adverse effects of interferon therapy. However, a more serious but rare side effect is thrombotic microangiopathy. We report the case of a 36-year-old Asian male patient with clinical manifestations of hypertension, blurred vision, acute renal failure, thrombocytopenia, and thrombotic microangiopathy. Renal biopsy showed interstitial edema with fibrosis, arteriolar thickening with vitreous changes, and epithelial podocytes segmental fusion. Immunofluorescence microscopy showed C3(+), Ig A(+) deposition in the mesangial region, which was pathologically consistent with thrombotic microangiopathy renal injury and Ig A deposition. The patient had a history of hepatitis B virus infection for more than 5 years. Lamivudine was used in the past, but the injection of long-acting interferon combined with tenofovir alafenamide fumarate was used since 2018. The comprehensive clinical investigation and laboratory examination diagnosed the condition as thrombotic microangiopathy kidney injury caused by interferon. After stopping interferon in his treatment, the patient’s renal function partially recovered after three consecutive therapeutic plasma exchange treatments and follow-up treatment without immunosuppressant. The renal function of the patient remained stable. This report indicates that interferon can induce thrombotic microangiopathy with acute renal injury, which can progress to chronic renal insufficiency.

IgA vasculitis nephritis (IgAVN) and IgA nephropathy (IgAN) share several clinical and pathological characteristics, though distinctions also exist. Their interrelation, however, remains undefined. This study investigates the clinicopathological divergences and prognostic disparities in pediatric patients with IgAVN and IgAN. Our study encompasses 809 pediatric patients with IgAVN and 236 with IgAN, all of whom underwent kidney biopsy. We utilized the Semiquantitative Classification (SQC) scoring system to juxtapose the pathologies of the two conditions, and performed a COX regression analysis to examine factors influencing their prognoses. Both patient groups demonstrated a predominance of males. A seasonality was observed, with a higher incidence of IgAN in the summer, and IgAVN in the fall (P < 0.0001). Patients with IgAN exhibited more severe tubulointerstitial injury, higher chronicity index, and total biopsy scores compared to those with IgAVN (P < 0.0001). Mesangial deposition intensity of complement C3, and the rate of pure IgA deposition, were found to be greater in patients with IgAVN compared to those with IgAN (P < 0.0001). The intensity of IgA deposition was also significantly higher in IgAVN patients (P = 0.003). IgAVN demonstrated a superior prognosis, with a higher rate of kidney remission (P < 0.0001). COX regression analysis indicated that interstitial fibrosis, as identified in the SQC pathology system, was associated with the prognosis of both conditions. Furthermore, the findings suggest that IgA deposition levels (IgA + + and IgA + + +) could potentially influence the prognosis of IgAVN. Compared to IgAVN, IgAN manifests more severely with regard to renal impairment, interstitial damage, and prognosis. The disparities in immune complex deposition levels and locations within the kidneys support the hypothesis of IgAVN and IgAN as distinct diseases. Interstitial fibrosis may serve as a key pathological indicator within the SQC system associated with kidney prognosis in children with IgAVN and IgAN. The degree of IgA deposition could also be linked with the prognosis of IgAVN.

OBJECTIVES:To investigate the clinical characteristics, pathology, and prognosis of children with diffuse endocapillary proliferative Henoch-Schönlein purpura nephritis (DEP-HSPN). METHODS:A retrospective analysis was performed on the clinical, pathological, and prognosis data of 44 children with DEP-HSPN and 765 children without DEP-HSPN. The children with DEP-HSPN were diagnosed by renal biopsy in Jiangxi Provincial Children's Hospital from January 2006 to December 2021. RESULTS:Among the 809 children with purpura nephritis, 44 (5.4%) had DEP-HSPN, with a mean age of (8±3) years, and there were 29 boys (65.9%) and 15 girls (34.1%). Compared with the non-DEP-HSPN group, the DEP-HSPN group had a significantly shorter time from onset to renal biopsy and a significantly higher proportion of children with respiratory infection or gross hematuria, and most children had nephrotic syndrome. The DEP-HSPN group had significantly higher levels of 24-hour urinary protein, urinary protein grading, microscopic hematuria grading, serum creatinine, and blood urea nitrogen and significantly lower levels of serum albumin and complement C3 (P<0.05). The DEP-HSPN group had a higher pathological grading, with predominant deposition of IgA in the mesangial area and capillary loops, and higher activity scores in the modified semi-quantitative scoring system (P<0.05). The Kaplan-Meier survival analysis showed that there was no significant difference in the renal complete remission rate between the two groups (P>0.05). CONCLUSIONS:Children with DEP-HSPN have a rapid onset, severe clinical manifestations and pathological grading, and high activity scores in the modified semi-quantitative scoring system. However, most of the children with DEP-HSPN have a good prognosis, with a comparable renal complete remission rate to the children without DEP-HSPN.

Objective To investigate the characteristics of renal pathological grades in Henoch–Schönlein purpura nephritis (HSPN) children with mild to moderate proteinuria and the correlation between pathological grade and severity of proteinuria among this population. Methods HSPN children who were presented with mild (150 mg <24 h urinary protein <25 mg/kg) to moderate (25 mg/kg ≤24 h urinary protein <50 mg/kg) proteinuria and performed renal biopsy without steroid ± immunosuppressant treatment in the Second Xiangya Hospital between January 2010 and March 2021 were involved. We retrospectively analyzed the correlation between age, disease course, degree of proteinuria, type of immunoglobulin deposits, C3 deposits in glomeruli and renal pathological grade. Results (1) 72 HSPN children including 46 boys and 26 girls were included, with a mean age of onset of 9.01 ± 2.65 years old. The majority of these patients (62.5%) had a disease course between 1 week to 1 month. 51 patients presented with mild proteinuria and 21 patients with moderate proteinuria. (2) Renal biopsy results showed that ISKDC Grade IIIa were both predominant in mild proteinuria group (25, 49%) and moderate proteinuria group (11, 52.4%). 32 patients had grade II (44.4%), 2 had grade IIIb (2.8%), 1 had grade IV (1.4%), and 1 had grade VI (1.4%). There was no correlation between age, disease course and renal pathological grade (p > 0.05). (3) In patients with mild proteinuria (n = 51), 27 (52.9%) HSPN children had a pathological grade ≥ grade III. In patients with moderate proteinuria (n = 21), 13 (61.9%) HSPN children had grade ≥ III. There was no significant difference in the proportion of renal pathological grade between the 2 groups (p > 0.05). (4) There was no significant correlation between glomerular C3 deposits or immunoglobulin deposit types and renal pathological grade (p = 0.776 and p = 0.056 respectively). Conclusion In HSPN children with mild to moderate proteinuria, longer disease course or heavier urinary protein level is not completely parallel with higher renal pathological grade. ISKDC grade IIIa is the most common pathological grade. Clinicians should pay great attention to the renal injury in patients with mild to moderate proteinuria.

ObjectivesTo explore the risk factors for renal damage in childhood immunoglobulin A vasculitis (IgAV) within 6 months and construct a clinical model for individual risk prediction.MethodsWe retrospectively analyzed the clinical data of 1,007 children in our hospital and 287 children in other hospitals who were diagnosed with IgAV. Approximately 70% of the cases in our hospital were randomly selected using statistical product service soltions (SPSS) software for modeling. The remaining 30% of the cases were selected for internal verification, and the other hospital's cases were reviewed for external verification. A clinical prediction model for renal damage in children with IgAV was constructed by analyzing the modeling data through single-factor and multiple-factor logistic regression analyses. Then, we assessed and verified the degree of discrimination, calibration and clinical usefulness of the model. Finally, the prediction model was rendered in the form of a nomogram.ResultsAge, persistent cutaneous purpura, erythrocyte distribution width, complement C3, immunoglobulin G and triglycerides were independent influencing factors of renal damage in IgAV. Based on these factors, the area under the curve (AUC) for the prediction model was 0.772; the calibration curve did not significantly deviate from the ideal curve; and the clinical decision curve was higher than two extreme lines when the prediction probability was ~15–82%. When the internal and external verification datasets were applied to the prediction model, the AUC was 0.729 and 0.750, respectively, and the Z test was compared with the modeling AUC, P > 0.05. The calibration curves fluctuated around the ideal curve, and the clinical decision curve was higher than two extreme lines when the prediction probability was 25~84% and 14~73%, respectively.ConclusionThe prediction model has a good degree of discrimination, calibration and clinical usefulness. Either the internal or external verification has better clinical efficacy, indicating that the model has repeatability and portability.Clinical trial registration:www.chictr.org.cn, identifier ChiCTR2000033435.

Objective. To investigate the effectiveness of moxibustion combined with Chinese medicine in the treatment of spleen and stomach deficiency cold-type gastroparesis by meta-analysis and to provide the clinical basis for its treatment. Methods. A computer search of eight databases was performed for published and unpublished randomized controlled trials on moxibustion for spleen and stomach deficiency cold-type stomach pain from domestic and international clinical trial centers. The study was divided into a combination of a moxibustion and Chinese medicine group and a regular Western medicine group, and the outcome indicators were “effective” and “ineffective.” The relative risk (RR) was used as the effect indicator for the dichotomous data, and the meta-analysis was performed using Reviewer Manager 5.4 and Stata17.0 software. Results. A total of 8 randomized controlled studies with 729 patients were included, and all studies were analyzed for comparability of patients’ baseline information, with no statistically significant differences found ( P > 0.05 ). The meta-analysis results showed that the pooled effect size RR for the eight studies was 1.24 (95% confidence interval 1.16–1.32), and the statistical significance test was Z = 6.69 ( P < 0.05 ), indicating that the difference was statistically significant. Conclusion. The meta-analysis concluded that the efficacy of moxibustion combined with Chinese medicine for the treatment of spleen and stomach deficiency cold-type gastroparesis was superior to that of regular Western medicine, but more high-quality studies are needed to confirm this finding.

Background This study aimed to investigate the correlation between immune infiltration and tumor mutational burden (TMB) in papillary thyroid carcinoma. Methods Transcriptome sequencing data sets, gene mutation data sets, and clinical data sets were downloaded from The Cancer Genome Atlas (TCGA) database. The immune and papillary carcinoma stromal scores were calculated using the "Estimate" package of R software. The relationship between the immune score, stromal score, TMB, and papillary thyroid carcinoma progression-free survival was analyzed. Pearson's test was used to analyze the correlation between the immune score, stromal score, and TMB. Results The stromal score and immune score of papillary thyroid carcinoma tissue were lower than those of normal thyroid tissue (P=0.008 and P<0.001, respectively). There was no significant difference in progression-free survival between the high stromal and low stromal score groups (P=0.075). The progression-free survival of the high immune score group was better than that of the low immune score group (P=0.029), and the progression-free survival of the low TMB group was better than that of the high TMB group (P<0.001). The high immune score, low TMB group had the best prognosis (P=0.003). Univariate Cox analysis showed that age, pathological stage, and TMB were risk factors for progression-free survival [hazard ratio (HR) >1, P<0.05], and that the immune score was a protective factor for progression-free survival (HR <1, P<0.05). Multivariate Cox analysis showed that age and TMB were independent risk factors for progression-free survival (HR >1, P<0.05), and that the immune score was an independent protective factor for progression-free survival (HR <1, P<0.05). Correlation analysis showed that the immune and stromal score were both negatively correlated with TMB (r=-0.26, P=0.031 and r=-0.41, P=0.028, respectively). Conclusions The immune and stromal scores of papillary thyroid carcinoma were negatively correlated with TMB. Thyroid cancer gene mutations inhibit immune cell infiltration and alter the thyroid cancer microenvironment. The immune score was an independent protective factor for progression-free survival, while TMB was an independent risk factor, both of which can be used for clinical prognosis assessment. Combined immunological and genomic analysis of papillary thyroid carcinoma can reveal potential prognostic markers and therapeutic targets and provide clues for the tumor immune escape mechanism.

Primary glomerular disease was the leading cause of chronic kidney disease (CKD) in China; however, changes in the economy and environment introduce variations in the spectrum of kidney diseases. This study aimed to analyze renal biopsy data to inform disease prevention and public health interventions. In this retrospective cohort study, data from 2,803 consecutive renal biopsies conducted at our center between January 2010 and December 2018 were analyzed. The sample was disaggregated by age and the date of biopsy to facilitate analysis. Primary glomerulonephritis (PGN) is the most frequent (81.84%) finding, followed by secondary glomerulonephritis (SGN; 15.38%), tubulointerstitial nephritis (15.38%), and others (1.57%). IgA nephropathy (IgAN), idiopathic membranous nephropathy (iMN), and minimal change disease were the primary causes of PGN. Among PGN cases, the incidence of iMN arose, especially among those aged ≥ 60 years old, during the observation period. Contrary to the case of iMN, the proportion of IgAN in PGN trended downward, continuously, and at length. Moreover, IgAN mainly affected those aged 25–44 years old and less so those aged ≥ 60 years old. Lupus nephritis, Henoch–Schönlein purpura nephritis, and diabetic nephropathy (DN) were key causes of SGN. A ratio reversal between infectious disease and chronic disease dramatically changed SGN patterns. In the past year, the incidence of hepatitis B–related nephritis has constantly declined; however, the proportion of DN among SGN had steadily increased. The incidence of iMN significantly increased during these years. Among SGN cases, the proportion of DN has increased.

Background Atypical hemolytic uremic syndrome, also called the nondiarrheal form of hemolytic uremic syndrome, is a rare disease characterized by the triad of thrombocytopenia, Coomb's test-negative microangiopathic hemolytic anemia, and acute renal failure. Approximately 60% of cases of atypical hemolytic uremic syndrome are associated with deficiencies of the complement regulatory protein, including mutations in complement factor H, complement factor I, or the membrane co-factor protein. Case presentation We report the case of a 26-year-old Asian man who presented with pulmonary infection, elevated blood pressure, microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Renal biopsy revealed diffuse capillary fibrin deposition, endothelial swelling, and arteriole narrowing like "onion skinning" consistent with thrombotic microangiopathy. Bidirectional sequencing of CFH, CFHR5, CFHR1, CFI, DGKE, CFB, and MCP confirmed that the patient was heterozygous for a novel missense mutation, p.Cys67Phe, in CFI. This patient had rapid evolution to end-stage renal disease and needed renal replacement therapy. Plasma exchange seemed inefficacious in this patient. Conclusions This report confirms the importance of screening patients with atypical hemolytic uremic syndrome for mutations in genes involved in complement system to clarify the diagnosis and demonstrates the challenges in the management of these patients.

Abstract Background Idiopathic membranous nephropathy (iMN) is recognized as an organ-specific autoimmune disease, mainly caused by anti-PLA2R antibody. This study aimed to study between anti-PLA2R antibody level at diagnosis and the response to tacrolimus (TAC)-based treatment in iMN patients. Methods This was a retrospective cohort study including 94 kidney biopsy-proven MN patients with positive anti-PLA2R antibody at diagnosis from May 2017 to September 2021 in our center. All iMN patients received the TAC regimen as the initial immunosuppressive therapy. All patients were divided into two groups according to anti-PLA2R antibody titer at diagnosis: high-level group (> 150 RU/ml; n = 42) and low-level group (≤ 150 RU/ml; n = 52). The association between anti-PLA2R antibody levels and clinical outcomes was assessed using the Kaplan–Meier method. Results The low density lipoprotein in the high-level group was significantly higher than low-level group at diagnosis, otherwise, serum albumin was significantly lower than low-level group; however, there was no significant difference in creatinine levels between two groups. The remission rates were significantly higher in the low-level group than high-level group after treatment with TAC for 12, 18, or 24 months (all P < 0.05). After 12 months of treatment with TAC, 82.7% of the patients in the low-level group achieved complete remission (CR) or partial remission (PR) (mean, 6.52 ± 0.53 months). However, 38.1% of the patients in high-level group achieved CR or PR (mean, 9.86 ± 0.51 months). Moreover, CR rate at 12 months in the high-level group was only 4.7% (mean, 11.88 ± 0.63 months). The infection frequency in the high-level group (35.6%) was higher than the low-level group (20%) during the TAC treatment, although there was no significant difference (P = 0.065). There were 19% patients who had end-stage kidney disease (ESKD), and 7.1% of patients died of ESKD in the high-level group during the follow-up period. Conclusion Anti-PLA2R antibody level above 150 RU/ml at diagnosis can predict a poor treatment response and outcome of TAC treatment in iMN patients, who may not benefit from TAC or other calcineurin inhibitor regimens as the initial treatment.

利妥昔单抗(Rituximab,RTX)是一种人鼠嵌合型单克隆抗体,特发性膜性肾病(idiopathic membranous ne-phropathy,IMN)是由针对肾小球足细胞分子的自身抗体所致.文章综述RTX在IMN中应用的研究进展,从而为IMN的临床治疗提供重要的理论依据和新思路.

Abstract Background and objectives: Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain uncertain. This meta-analysis aimed to investigate the efficacy and safety of RTX in patients with membranous nephropathy. Methods: A literature search was performed using Pubmed, Embase, OVID, and Cochrane Library and randomized controlled trials (RCTs) case-controls and cohort studies published till 30 July 2019 were assessed. The studies assessing the efficacy and safety of RTX in patients with membranous nephropathy were included. Results: Eight relevant trials involving 542 patients were included in the meta-analysis. It was found that RTX did not significantly improve serum albumin levels and e-GFR when compared with the control group (including cyclosporine and cyclophosphamide, chlorambucil, prednisone, non-immunosuppressive anti-proteinuria treatment), serum albumin levels (OR = 0.31, 95%CI–0.12–0.74, P = .15), e-GFR (OR = –1.49, 95%CI–17.14–14.17, P = .85). However, RTX did reduce the serum creatinine (OR = –0.01, 95%CI–0.36–0.34, P = .95) and urinary protein (OR = –2.39, 95%CI –7.30 –2.53, P = .34) levels. Also, in comparison to the control group, RTX did improve the total remission rate (OR = 1.63, 95%CI 0.48–5.54, P = .43), achieve a higher rate of complete remission (OR = 2.54, 95%CI 1.65–3.90, P < .01) and also reduced the amount of M-type phospholipase A2 receptor-Antibody depletion in patients (OR = 5.59, 95%CI 1.81–17.2, P = .003). RTX-related adverse events were mostly mild (most infusion-related reactions) in nature and serious adverse events were rare. Conclusion: RTX proved to be efficient, well-tolerated and a safe drug in the treatment of membranous nephropathy. Most patients reach complete remission during the follow-up period, and relapse is rare. RTX may turn out to be promising in membranous nephropathy patients.

The present study analyzed the clinicopathological features and prognosis in patients with idiopathic membranous nephropathy (IMN) with hypertension. In the hypertension group, significant differences were found in the age, hypertension history, systolic blood pressure, diastolic blood pressure (DBP), mean arterial pressure, albumin, serum creatinine, low-density lipoprotein, 24 h urine protein levels, calculated estimated glomerular filtration rate (e-GFR), glomerular sclerosis, segmental sclerosis, ischemic sclerosis, interstitial fibrosis, tubular atrophy and vascular lesion compared with the non-hypertension group (P<0.05). The average follow-up time was 35.70 months (5.10-103.77 months). In total, 54 patients reported a 50% decline in e-GFR, eight patients reported progression of disease to end-stage renal disease (ESRD) and nine cases of mortality were reported. Survival analysis results suggested that patients with hypertension had a lower cumulative renal survival rate than those without hypertension (P=0.034). Multivariate Cox hazards regression analysis results suggested that DBP [hazard ratio (H), 5.160; CI, 0.865-0.989; P=0.023], age (H, 4.839; CI, 1.008-1.142; P=0.028), sex (H, 5.680; CI, 0.031-0.714; P=0.017), serum creatinine (H, 20.920; CI, 1.035-1.089; P<0.001), uric acid (H, 4.783; CI, 0.982-0.0.999; P=0.029), 24 h urine protein (H, 6.318; CI, 1.079-1.850; P=0.012), e-GFR (H, 4.008; CI, 1.001-1.062; P=0.045) and glomerular sclerosis (H, 8.722; CI, 1.860-21.559; P=0.003), segmental sclerosis (H, 7.737; CI, 7.770-13.219; P=0.005), percentage of ischemic sclerosis (H, 4.729; CI, 1.444-11.945; P=0.030), crescents (H, 5.938; CI, 0.003-0.526; P=0.015), interstitial fibrosis and tubular atrophy (H, 8.128; CI, 0.005-1.052; P=0.043), and vascular lesion (H, 4.049; CI, 1.030-9.766; P=0.044) were risk factors for the development of IMN into ESRD. The results suggested that DBP may be an independent risk factor for the development of IMN with hypertension.