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To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007–2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

Chronic kidney disease (CKD) is prevalent globally with limited therapeutic drugs available. To systemically identify novel proteins involved in the pathogenesis of CKD and possible therapeutic targets, we integrated human plasma proteomes with the genome-wide association studies (GWASs) of CKD, estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN) to perform proteome-wide association study (PWAS), Mendelian Randomization and Bayesian colocalization analyses. The single-cell RNA sequencing data of healthy human and mouse kidneys were analyzed to explore the cell-type specificity of identified genes. Functional enrichment analysis was conducted to investigate the involved signaling pathways. The PWAS identified 22 plasma proteins significantly associated with CKD. Of them, the significant associations of three proteins (INHBC, LMAN2, and SNUPN) were replicated in the GWASs of eGFR, and BUN. Mendelian Randomization analyses showed that INHBC and SNUPN were causally associated with CKD, eGFR, and BUN. The Bayesian colocalization analysis identified shared causal variants for INHBC in CKD, eGFR, and BUN (all PP4 > 0.75). The single-cell RNA sequencing revealed that the INHBC gene was sparsely scattered within the kidney cells. This proteomic study revealed that INHBC, LMAN2, and SNUPN may be involved in the pathogenesis of CKD, which represent novel therapeutic targets and warrant further exploration in future research.

IntroductionCircadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed.MethodsA national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR

Background Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine malignancy, of which >40% present with glucocorticoid excess. Glucocorticoids and glucocorticoid receptor (GR) signaling have long been thought to suppress immunity and promote tumor progression by acting on immune cells. Here, we provide new insights into the interaction between GR signaling activity and the immune signature of ACC as a potential explanation for immune escape and resistance to immunotherapy.Methods First, GR immunohistochemical staining and immunofluorescence analysis of tumor-infiltrating lymphocyte (CD4 T, CD8 T cells, natural killer (NK) cells, dendritic cells and macrophages) were performed in 78 primary ACC tissue specimens. Quantitative data of immune cell infiltration in ACC were correlated with clinical characteristics. Second, we discovered a GR activity signature (GRsig) using GR-targeted gene networks derived from global gene expression data of primary ACC. Finally, we identified two GRsig-related subtypes based on the GRsig and assessed the differences in immune characteristics and prognostic stratification between the two subtypes.Results GR was expressed in 90% of the ACC tumors, and CD8+ cytotoxic T lymphocytes were the most common infiltrating cell type in ACC specimens (88%, 8.6 cells/high power field). GR expression positively correlated with CD8+ T cell (Phi=0.342, p

Abstract. Background:. Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. Methods:. From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. Results:. After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P = 0.787, P = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs. 10.5%, P = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR (P = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12–0.78, P = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen (P = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01–7.31, P = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. Conclusions:. An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.

BackgroundCurrent guidelines do not recommend routine antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in non-liver solid organ transplant (SOT) recipients with resolved HBV infection, even in anti-hepatitis B surface antigen (anti-HBs)-negative recipients and those receiving intense immunosuppression. This systematic review and meta-analysis aimed to determine the incidence, risk factors, and clinical outcomes of HBV reactivation in non-liver SOT recipients.Methods and findingsThree databases (PubMed, Embase, and Cochrane Library) were systematically searched up to December 31, 2022. Clinical studies reporting HBV reactivation in non-liver SOT recipients were included. Case reports, case series, and cohort studies with a sample size of less than 10 patients were excluded. Random-effects analysis was used for all meta-analyses. We included 2,913 non-liver SOT recipients with resolved HBV infection from 16 retrospective cohort studies in the analysis. The overall HBV reactivation rate was 2.5% (76/2,913; 95% confidence interval [95% CI 1.6%, 3.6%]; I2 = 55.0%). Higher rates of reactivation were observed in recipients with negative anti-HBs (34/421; 7.8%; 95% CI [5.2%, 10.9%]; I2 = 36.0%) by pooling 6 studies, experiencing acute rejection (13/266; 5.8%; 95% CI [2.3%, 14.5%]; I2 = 63.2%) by pooling 3 studies, receiving ABO blood type-incompatible transplantation (8/111; 7.0%; 95% CI [2.9%, 12.7%]; I2 = 0%) by pooling 3 studies, receiving rituximab (10/133; 7.3%; 95% CI [3.4%, 12.6%]; I2 = 0%) by pooling 3 studies, and receiving anti-thymocyte immunoglobulin (ATG, 25/504; 4.9%; 95% CI [2.5%, 8.1%]; I2 = 49.0%) by pooling 4 studies. Among recipients with post-transplant HBV reactivation, 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) developed HBV-related hepatic failure, and 11.0% (7/52; 95% CI [4.0%, 20.8%]; I2 = 0.3%) had HBV-related death. Negative anti-HBs (crude odds ratio [OR] 5.05; 95% CI [2.83, 9.00]; p < 0.001; I2 = 0%), ABO blood type-incompatible transplantation (crude OR 2.62; 95% CI [1.05, 6.04]; p = 0.040; I2 = 0%), history of acute rejection (crude OR 2.37; 95% CI [1.13, 4.97]; p = 0.022; I2 = 0%), ATG use (crude OR 3.19; 95% CI [1.48, 6.87]; p = 0.003; I2 = 0%), and rituximab use (crude OR 3.16; 95% CI [1.24, 8.06]; p = 0.016; I2 = 0%) increased the risk of reactivation. Adjusted analyses reported similar results. Limitations include moderate heterogeneity in the meta-analyses and that most studies were conducted in kidney transplant recipients.ConclusionsNon-liver SOT recipients with resolved HBV infection have a high risk of HBV-related hepatic failure and HBV-related death if HBV reactivation occurs. Potential risk factors for HBV reactivation include rituximab use, anti-thymocyte immunoglobulin use, anti-HBs negative status, acute rejection history, and ABO blood type-incompatible transplantation. Further research on monitoring and routine antiviral prophylaxis of non-liver SOT recipients at higher risk of HBV reactivation is required.

BackgroundDeceased donor kidney transplantation (DDKT) is a major therapeutic option for patients with end-stage renal diseases. Although medical techniques improved in recent years, acute or chronic rejection after DDKT is not uncommon and often results in poor graft survival. Therefore, the determination of risk factors is very important to stratify patients and to improve outcomes. This study aims to evaluate the risk factors for treated rejection (TR) of patients after DDKT.MethodsClinical data of deceased donors and corresponding recipients were retrospectively collected. The primary outcome was TR defined as the treatment for rejection within 24 months after DDKT. Univariate comparisons of baseline characteristics were performed with Chi-square test, t-test, and Mann–Whitney U test. Logistic regression was constructed to analyze potential risk factors. Receiver operating characteristic (ROC) curve and Jordan index were generated to determine the optimal cutoff value. The association between continuous variables and TR was examined and visualized by using restricted cubic spline (RCS) models.ResultsData of 123 deceased donors and 246 recipients were obtained and analyzed. The median age was 41 (4–62) years for recipients and 39 (1–65) years for donors. The recipients who died or suffered graft loss during the follow-up period were 8 (3.3%) and 12 (4.9%), respectively. After univariate analysis and subsequent multivariate analysis, the preoperative serum uric acid (OR, 2.242; 95% CI, 1.037–4.844; P = 0.040), platelet (OR, 2.163; 95% CI, 1.073–4.361, P = 0.031), absolute neutrophil count (OR, 2.183; 95% CI, 1.025–4.649; P = 0.043), and HLA-DQ mismatch (OR, 2.102; 95% CI, 1.093–4.043; P = 0.026) showed statistical significance. RCS models showed that patients with higher levels of uric acid had increased risk of TR.ConclusionsSerum uric acid and other three indicators were found to be the independent risk factors for TR, which may contribute to stratify patients and develop personalized regimen in perioperative period.

Abstract Background Currently, research on the quantitative distribution of ABO antigens in different organs and tissues remains limited. We aimed to examine the individual characteristics of blood group glycoprotein A and B antigen expression in human kidneys and livers. Methods We obtained human samples, including the renal artery, renal vein, renal tissue, hepatic artery, hepatic vein, portal vein, and hepatic tissue, from 24 deceased organ transplant donors. The expression of the blood group antigens glycoprotein A and B was analysed and compared by Western blotting. Results There was no significant difference in the expression between blood group glycoprotein A and B antigens at any of the seven sites (p > 0.05). The expression of both A and B antigens was highest in renal tissue and the portal vein and was lowest in the renal artery. A large difference in glycoprotein antigen expression was observed among various donors or different regions of the same individual. Univariate analysis revealed that glycoprotein A/B antigens were affected by the age and sex of donors and were significantly higher in males and in young people. Conclusions Our study found that blood group glycoprotein antigen expression showed certain trends and distinct distribution in the kidney, liver, and vessels among individuals and in different regions of the same individual, which may explain the different clinical outcomes of patients who received ABO-incompatible transplantation.

BackgroundTo better understand the characteristics, and survival outcomes of synchronous renal cell carcinoma (RCC) and urothelial carcinoma (UC), we described and analyzed the clinical features, factors, and prognosis of patients with synchronous RCC and UC using a large population-based database.MethodsWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016), we identified patient with concurrent RCC and UC at initial diagnosis. Their clinicopathological features and prognosis were evaluated. A logistic regression model was used to examine risk factors for the occurrence of concomitant RCC and UC, and Kaplan-Meier survival curves were used to estimate overall survival.ResultsA total of 61,454 RCC patients were identified from the SEER database, 704 (1.1%) patients presented with synchronous RCC and UC. Among these patients, concurrent bladder tumors (566/704) are more common. Subsequently, subgroup analysis based on the location of UC indicated that patients with concurrent RCC and upper tract urothelial carcinoma (UTUC) had unfavorable UC characteristics (higher tumor stage and grade), compared with patients with concomitant bladder cancer. An increased risk of concurrent UC was observed among older age, male sex, and white race. Meanwhile, papillary RCC histology [odds ratio (OR) 3.23; 95% confidence interval (CI) 2.13–4.90], and smaller tumor (OR 6.63; 95% CI 4.46–9.87) were independent risk factors for concomitant UTUC. In addition, we found that synchronous RCC and UTUC was associated with worse survival by using Kaplan-Meier and multivariable analysis [hazard ratio (HR) 2.36, 95% CI 1.89–2.95]. However, concomitant bladder cancer did not affect survival outcomes of patients with RCC (HR 1.00, 95% CI 0.86–1.17).ConclusionWe found that synchronous concurrent RCC and UC is relatively uncommon and mostly located in the bladder. Older age, male sex, and white race increase the risk of synchronous RCC and UC. Meanwhile, patients with papillary RCC histology, and smaller tumors are more likely to have concomitant RCC and UTUC. Furthermore, our findings suggest that synchronous RCC and UTUC has a worse prognosis, while, concomitant bladder tumor did not affect the oncological outcomes of RCC.

Background: Cuprotosis is a new form of programmed cell death induced by copper. We explored the correlation of cuprotosis with clear cell renal cell carcinoma (ccRCC) and constructed a cuprotosis-related signature to predict the prognosis of patients with ccRCC.Methods: The clinical and transcriptomic data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA), cBioPortal, and GEO databases, and cuprotosis-related gene sets were contained in the previous study. A cuprotosis-related signature was developed based on data from TCGA and verified by data from cBioPortal and GEO databases. The immune cell infiltrates and the corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correlation of the signature risk score with immune therapy response.Results: A signature containing six cuprotosis-related genes was identified and can accurately predict the prognosis of ccRCC patients. Patients with downregulated copper-induced programmed death had a worse overall survival (hazard ratio: 1.90, 95% CI: 1.39–2.59, p < 0.001). The higher signature risk score was significantly associated with male gender (p = 0.026), higher tumor stage (p < 0.001), and higher histological grade (p < 0.001). Furthermore, the signature risk score was positively correlated with the infiltration of B cells, CD8+ T cells, NK cells, Tregs, and T cells, whereas it was negatively correlated with eosinophils, mast cells, and neutrophils. However, no correlation between cuprotosis and response to anti-PD-1 therapy was found.Conclusion: We established a cuprotosis signature, which can predict the prognosis of patients with ccRCC. Cuprotosis was significantly correlated with immune cell infiltrates in ccRCC.

BackgroundThe upregulation of amino acid metabolism is an essential form of metabolic reprogramming in cancer. Here, we developed an amino acid metabolism signature to predict prognosis and anti-PD-1 therapy response in clear cell renal cell carcinoma (ccRCC).MethodsAccording to the amino acid metabolism-associated gene sets contained in the Molecular Signature Database, consensus clustering was performed to divide patients into two clusters. An amino acid metabolism-associated signature was identified and verified. Immune cell infiltrates and their corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correspondence between the signature risk score and the immune therapy response.ResultsTwo clusters with different amino acid metabolic levels were identified by consensus clustering. The patients in the two clusters differed in overall survival, progression-free survival, amino acid metabolic status, and tumor microenvironment. We identified a signature containing eight amino acid metabolism-associated genes that could accurately predict the prognosis of patients with ccRCC. The signature risk score was positively correlated with infiltration of M1 macrophages, CD8+ T cells, and regulatory T cells, whereas it was negatively correlated with infiltration of neutrophils, NK cells, and CD4+ T cells. Patients with lower risk scores had better overall survival but worse responses to nivolumab.ConclusionAmino acid metabolic status is closely correlated with tumor microenvironment, response to checkpoint blockade therapy, and prognosis in patients with ccRCC. The established amino acid metabolism-associated gene signature can predict both survival and anti-PD-1 therapy response in patients with ccRCC.

Abstract Background Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. Given the limited treatment options, prognostic assessment of ACC is increasingly crucial. In this study, we aim to assess the correlation between preoperative serum albumin and prognosis in patients with ACC after primary resection. Methods We retrospectively collected and reviewed medical information about 71 ACC patients who underwent primary resection. Survival analysis was performed by Kaplan–Meier analysis with log-rank test or Breslow test. Receiver operating characteristic (ROC) curve and Jordan index was generated to explore optimal cut-off value of albumin. Univariate and multivariate analysis was conducted using Cox’s hazards model. Statistical significance was defined as P

Background: Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets.Methods: The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database. A consensus clustering algorithm was then conducted to classify the patients into two clusters. Tumor prognosis, clinicopathological features, mutations, functional analysis, ferroptosis status analysis, immune infiltration, immune checkpoint-related gene expression level, chemotherapy resistance, and tumor stem cells were analyzed between clusters. An energy metabolism-related signature was further developed and verified using data from cBioPortal datasets.Results: Two clusters (C1 and C2) were identified using a consensus clustering algorithm based on an energy metabolism-related signature. The patients with subtype C1 had more metabolism-related pathways, different ferroptosis status, higher cancer stem cell scores, higher chemotherapy resistance, and better prognosis. Subtype C2 was characterized by an increased number of advanced BLCA cases and immune-related pathways. Higher immune and stromal scores were also observed for the C2 subtype. A signature containing 16 energy metabolism-related genes was then identified, which can accurately predict the prognosis of patients with BLCA.Conclusion: We found that the energy metabolism-associated subtypes of BLCA are closely related to the immune microenvironment, immune checkpoint-related gene expression, ferroptosis status, CSCs, chemotherapy resistance, prognosis, and progression of BLCA patients. The established energy metabolism-related gene signature was able to predict survival in patients with BLCA.

Aim: High prevalence of metabolic disorders causes higher risk of cardiovascular diseases after kidney transplantation (KT), which remains the main burden impairing short-term and long-term survival. This open-label, prospective, randomized, 3-arm, controlled trial will evaluate the safety, tolerability and efficacy of metformin and empagliflozin in ameliorating metabolic profiles after KT.Methods: After a screening assessment, eligible patients with an estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2 are randomly assigned to standard triple immunosuppression alone, standard immunosuppression plus metformin (500 mg twice daily), standard immunosuppression plus empagliflozin (25 mg once daily) from discharge. The primary endpoint is the differences in the visceral-to-subcutaneous fat area ratio over 12 months, evaluated by magnetic resonance imaging (MRI). Secondary outcomes include kidney graft function, glycometabolism, lipid metabolism, and inflammatory parameters. The trial will enroll 105 kidney transplant recipients, providing 90% power to detect the difference at 5% significance.

BackgroundA systematic review and meta-analysis were performed to investigate the efficacy and safety of conversion from calcineurin inhibitors (CNIs) to mammalian target of rapamycin inhibitors (mTORi) in kidney transplant recipients (KTRs).MethodsMEDLINE, EMBASE, PubMed, and Cochrane Library were searched to identify randomized controlled trials (RCTs) that compared the continuation of CNI with conversion to mTORi therapy.ResultsTwenty-nine RCTs (5,747 KTRs) were included in our analysis. Meta-analysis of the glomerular filtration rate (SMD 0.20; 95%CI 0.10–0.31; P

IntroductionABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation.MethodsData of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection.ResultsOf the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004).ConclusionsA weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.

Abstract Background T follicular helper (Tfh) cells play a control role in contribution of B cell differentiation and antibody production. T follicular regulatory (Tfr) cells inhibit Tfh-B cell interaction. Methods To identify whether circulating Tfh (cTfh) and Tfr (cTfr) cells contribute to chronic renal allograft dysfunction (CAD), 67 kidney transplant recipients (34 recipients with CAD, 33 recipients with stable function) were enrolled. The frequency of cTfh and cTfr cells, the level of serum CXCL13 were measured. Results The frequency of cTfr cells in CAD group was significantly lower than that in stable group (0.31% vs 0.68%, P = 0.002). The cTfh to cTfr ratio in CAD group was significantly higher than that in stable group (55.4 vs 25.3, P = 0.013). Serum CXCL13 in CAD group was significantly higher than stable group (30.4 vs 21.9 ng/ml, P = 0.025). After linear regression analysis, the cTfh to cTfr ratio was an independent risk factor for estimated glomerular filtration rate (eGFR) in recipients (standardized coefficient = − 0.420, P = 0.012). After logistic regression analysis, the cTfh to cTfr ratio was an independent risk factor for CAD (OR = 1.043, 95%CI = 1.004–1.085, P = 0.031). Conclusion The imbalance between cTfh and cTfr cells contribute to the development of CAD.

ObjectivesThe aim of this study is to evaluate the significant factors influencing the overall survival (OS) and recurrence free survival (RFS) and make an attempt to develop a nomogram for predicting the prognosis of patients with genitourinary sarcoma (GS).MethodsData on adult GS from 1985 to 2010 were collected. The impact of clinical factors on OS and RFS were estimated by Kaplan–Meier (KM) analysis, and differences between groups were analyzed by the log-rank test. To establish a nomogram, all patients were randomly divided into a training set (n = 125) and a testing set (n = 63). Cox proportion hazard model was utilized to assess the prognostic effect of variables. Then, a nomogram was established to estimate 1-, 3-, and 5-year OS based on Cox regression model. Subsequently, the nomogram was validated by a training set and a validation set.ResultsA total of 188 patients were enrolled into our study. Male patients with bladder sarcoma had better OS rather than RFS when stratified by gender (P = 0.022). According to histological subtypes, patients with leiomyosarcoma (LMS) undergoing chemotherapy were associated with favorable OS (P = 0.024) and RFS (P = 0.001). Furthermore, LMS in kidney sarcoma were associated with lower recurrence rate in comparison to rhabdomyosarcoma (RMS) (P = 0.043). Margin status after surgical excision markedly influenced the OS and RFS of GS patients and negative margins presented optimal prognosis. Chemotherapy was associated with improved OS for patients without surgery (P = 0.029) and patients with positive margins (P = 0.026). Based on the multivariate analysis of the training cohort, age, gender, surgery status, histological subtype, and chemotherapy were included in our nomogram for prediction of OS. The nomogram had sufficient power with concordance index (C-index) of OS: 0.770, 95%CI: 0.760–0.772 and area under curve (AUC) of OS: 0.759, 95%CI: 0.658–0.859 in the training set and with C-index of OS: 0.741, 95%CI: 0.740–0.765, and AUC of OS: 0.744, 95%CI: 0.576–0.913 in the validation set.ConclusionsAdults GS is a group of extremely rare tumors with poor prognosis. Of all histological types, LMS is sensitive to chemotherapy. We highlighted the cardinal role of surgical resection and the importance of achieving negative margins. We identified the efficacy of chemotherapy for patients with positive margins and those without surgery as well. A nomogram is validated as an effective tool predicting short-term outcomes.

ObjectiveAberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect.Data SourcesDatabase including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved.ResultsCD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies.ConclusionCD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors.

Background: The aim of the present study was to investigate the impact of time in therapeutic range TTR on long-term outcomes of living kidney transplants.Methods: We included 1,241 living kidney transplants and randomized them into development and validation cohorts with a ratio of 2:1. The tacrolimus TTR percentage was calculated by linear interpolation with a target range (5–10 ng/ml months 0–3, 4–8 ng/ml months 4–12). The optimal TTR cutoff was estimated by the receiver operating characteristic curve analysis on the basis of acute rejection (AR) within 12 months in the development cohort. Outcomes were analyzed between patients with high TTR and low TTR in the development and validation cohorts, respectively. The TTR was also compared with other tacrolimus measures.Results: The optimal TTR cutoff value was 78%. In the development cohort, patients with TTR > 78% had significantly higher rejection- and infection-free survival. TTR < 78% was an independent risk factor for AR (OR: 2.97, 95%CI: 1.82–4.84) and infection (OR: 1.55, 95%CI: 1.08–2.22). Patient and graft survival were significantly higher in those with TTR>78%, and TTR

There is limited information on the role of miR-17-92 in renal tubular pathophysiology. Therefore, the present study was performed to determine whether miR-17-92 plays a role in ischemia-reperfusion injury (IRI)-induced acute kidney injury. We originally demonstrated that miR-17-92 is up-regulated following IRI in vivo. To explore the roles of miR-17-92 in the IRI process, we first generated a renal proximal tubule-specific miR-17-92 deletion (PT-miR-17-92−/−) knockout mouse model with Cre driven by the Kap promoter. We found that PT-deficient miR-17-92 mice had more severe renal dysfunction and renal structures than their littermates. Compared with sham-operated mice, both wide-type (WT) mice and PT-miR-17-92−/− mice showed increased serum levels of creatinine and urea. However, the levels of serum urea and creatinine in PT-miR-17-92−/− mice after the IRI operation were significantly higher than the levels in WT mice. In addition, PT-miR-17-92−/− mice showed higher levels of serum potassium and phosphonium after the IRI operation. Histological analysis revealed that PT-miR-17-92−/− mice had substantial histopathologic changes, such as tubular dilation and tubular necrosis. Overexpression of miR-17-92 could partially reverse the side-effects of IRI on the proximal tubules in vivo. Furthermore, we employed a quantitative proteomic strategy and identified 16 proteins as potential targets of miR-17-92. Taken together, our findings suggested that miR-17-92 may ameliorates IRI-induced acute kidney injury. Our results indicate that pharmacologic modulation of these miRNAs may have therapeutic potential for acute kidney injury. Keywords: Acute kidney injury, Ischemia reperfusion injury, miR-17-92

To investigate whether the ratio of remnant kidney volume to body weight (V/W ratio) can impact renal function in donors, 45 living kidney donors were enrolled. Kidney volume was analyzed by magnetic resonance imaging. Renal function was compared between donors with a V/W ratio of < 2.0 mL/kg (n = 23) or ≥ 2.0 mL/kg (n = 22). Donors in both V/W groups showed similar serum creatinine levels and estimated glomerular filtration rates (eGFRs) at 7 days and 1 year, whereas donors with a V/W ratio of < 2.0 mL/kg had significantly higher 24-hour urine protein levels at 1 year (0.54 ± 0.23 g/d vs. 0.33 ± 0.19 g/d, p = 0.028). Multivariate analysis revealed no correlation between the V/W ratio and eGFR at 7 days or 1 year, and a V/W ratio of < 2 mL/kg was not associated with an increased incidence of eGFR < 60 mL/min/1.73 m2 at 1 year (risk ratio 1.73, 95% confidence interval 0.10–29.47). The V/W ratio correlated inversely with 24-hour urine protein (r = −0.377, p = 0.021) at 1 year, and donors with a V/W ratio of < 2.0 mL/kg were more likely to show 24-hour urine protein >300 mg (risk ratio 1.70, 95% confidence interval 1.08–2.67) at 1 year. Donors with lower V/W ratios have higher 24-hour urinary protein levels at 1 year after transplantation. These findings suggest that the V/W ratio may be useful for kidney selection.

Antecedentes: La prevalencia de depresión en pacientes con síndrome de ovario poliquístico (SOPQ) es alta; un estudio ha revelado que supera en cuatro veces la de las pacientes sin SOPQ. Por lo tanto, es importante la evaluación sistemática de la efectividad y la seguridad de los antidepresivos para las pacientes con SOPQ. Objetivos: Evaluar la efectividad y la seguridad de los antidepresivos en cuanto al tratamiento de la depresión y otros síntomas en pacientes con SOPQ. Métodos de búsqueda: Se realizaron búsquedas en las siguientes bases de datos desde su inicio hasta junio de 2012: el registro de ensayos del Grupo Cochrane de Trastornos Menstruales y Subfertilidad (Cochrane Menstrual Disorders and Subfertility), el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, PsycINFO y Chinese National Knowledge Infrastructure, el metaRegister of Controlled Trials (controlled-trials.com), el National Institute of Health Clinical Trials register (clinicaltrials.gov) y en el portal de búsqueda de la World Health Organization International Trials Registry Platform (www.who.int/trialsearch/Default.aspx). Criterios de selección: Sólo se incluyeron en la revisión los ensayos controlados aleatorios (ECA) que estudiaban la efectividad y la seguridad de los antidepresivos en pacientes con SOPQ. Obtención y análisis de los datos: La calidad metodológica de los ensayos fue evaluada de forma independiente por dos revisores, de forma paralela a la extracción de datos. El riesgo de sesgo en los estudios incluidos se evaluó en seis dominios: 1. generación de secuencia: 2. ocultación de la asignación; 3. cegamiento de los participantes, personal y evaluadores de resultados; 4. completitud de los datos de resultado; 5. informe selectivo de los resultados; 6. otras fuentes potenciales de sesgo. Resultados principales: No se encontraron estudios que informaran ninguno de los resultados primarios de la revisión (puntuaciones de la depresión y del trastorno del estado de ánimo relacionado, calidad de vida y eventos adversos). Sólo un estudio con 16 mujeres era elegible para la inclusión. Este estudio comparó sibutramina versus fluoxetina en pacientes con SOPQ, e informó sólo resultados endócrinos y metabólicos. Estuvo poco claro si las participantes tenían problemas psicológicos al inicio. No se hallaron diferencias significativas entre los grupos para ninguno de los resultados medidos. Conclusiones de los autores: No existen pruebas sobre la efectividad y la seguridad de los antidepresivos para el tratamiento de la depresión y otros síntomas en pacientes con SOPQ.