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Background and aims. To investigate the clinical implications of serum HBV RNA, serum hepatitis B core-related antigen (HBcrAg), and quantitative anti-HBc in treatment-naïve patients with chronic HBV infection. Methods. A total of 111 patients in total from different disease phases were recruited, including 21 in immune-tolerant (IT) phase, 49 in immune-clearance (IC) phases, 29 in immune-control or low replicative (LR) phase, and 12 in reactivation phases. Serum HBV RNA, anti-HBc, HBcrAg, and intrahepatic covalently closed circular DNA (cccDNA) were quantified and each of these indicator’s correlation with liver inflammation was analyzed. Results. HBeAg-positive individuals had significant higher serum levels of HBV RNA and HBcrAg than those who were HBeAg negative, similar to that of serum HBV DNA. Comparatively, HBV RNA ( r =0.79, P < 0.01 ) and HBcrAg ( r =0.78, P < 0.01 ) had almost same higher overall correlation with the cccDNA, as that of HBV DNA ( r =0.81, P < 0.01 ). Serum anti-HBc level ( r = -0.52, P < 0.05 ) is negatively correlated with cccDNA level at IT phase rather than the other three phases. When set the cutoff value at 4.00 log10 IU/mL, serum anti-HBc showed potential to indicate liver inflammation, with AUC as 0.79 and the specificities as 78.85% for HBeAg positive, and with AUC as 0.72 and the specificities as 62.16% for HBeAg-negative patients, respectively. Conclusions. In treatment-naïve patients, levels of serological markers HBV RNA and HBcrAg could mirror intrahepatic cccDNA level, but were not superior to HBV DNA level. Serum anti-HBc level had certain potential to be used as a predicting marker for liver inflammation.

Aim: We performed a systematic review and network meta-analysis evaluating the safety and efficacy of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among dialysis chronic kidney disease patients.Methods: Safety was evaluated with any adverse events (AEs), serious adverse events (SAEs), and 12 common events. Efficacy was mainly analyzed with hemoglobin response. All reported results were summarized using mean difference and risk ratio (RR) with 95% confidence interval (CI). Publication bias was assessed through funnel plots.Results: Twenty trials (19 studies) with 14,947 participants were included, comparing six HIF-PHIs with erythropoiesis-stimulating agents (ESAs). No significant differences were indicated in overall AEs and SAEs between each HIF-PHI and ESA. The occurrence of gastrointestinal disorder was higher in enarodustat and roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52–31.40, p = 0.01; RR: 1.30, 95% CI: 1.04–1.61, p = 0.02). The occurrence of hypertension was lower in vadadustat than in ESAs (RR: 0.81, 95% CI: 0.69–0.96, p = 0.01). The occurrence of vascular-access complications was higher in roxadustat (RR: 1.15, 95% CI: 1.04–1.27, pppp = 0.04), whereas noticeable reductions were indicated in vadadustat (RR: 0.88, 95% CI: 0.82–0.94, pp = 0.02). There was no significant difference between daprodustat and ESAs (RR: 0.97, 95% CI: 0.89–1.06, p = 0.47).Conclusion: Although HIF-PHIs did not show significant differences from ESAs in terms of overall AEs and SAEs, statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications were observed between HIF-PHIs, which deserved to be noted in clinical decision making.Systematic review registration: This study is registered with PROSPERO (registration number CRD42022312252)

BACKGROUND Chatbots are increasingly used in health care to enhance patient engagement, satisfaction, and cost-effectiveness. However, chatbot acceptability varies among patient populations and has not been well studied in patients with autoimmune inflammatory rheumatic disease (AIIRD). OBJECTIVE To examine the acceptability of a chatbot designed explicitly for AIIRD. METHODS A survey was conducted in an outpatient setting at a tertiary rheumatology referral center, targeting patients who interacted with a chatbot developed explicitly for diagnosing and providing information on AIIRD. Based on the RE-AIM framework, the survey assessed the chatbots’ effectiveness, acceptability, and implementation. RESULTS A total of 200 patients with rheumatological conditions participated in the survey between June and October 2022 (100 first visits and 100 follow-up visits). The study demonstrated the overall high acceptability of chatbots in rheumatology, which remained consistent across age, gender, and visit type. The subgroup analysis indicated that individuals with higher educational backgrounds tended to be more receptive to chatbots as sources of information. Participants with inflammatory arthropathies also demonstrated a higher degree of chatbot acceptability as an information source than individuals with connective tissue disease. CONCLUSIONS Our study demonstrated that the chatbot had high acceptability among patients with AIIRD, independent of patient demographics or type of visit. Acceptability is more pronounced in patients with inflammatory arthropathies and in those with higher educational levels. Health care providers can use these insights when considering the implementation of chatbots in rheumatology to improve patient care and satisfaction.

Abstract Objective: This study investigated the impact of 24-hour urinary calcium excretion (UCaE) on renal function decline in hospitalized patients with and without chronic kidney disease (CKD). Methods: This study enrolled 3,815 CKD patients with stages 1-4, and 1,133 Non-CKD patients admitted to the First Center of the Chinese PLA General Hospital between January 2014 and July 2022. The primary outcome for CKD was a composite of CKD progression defined as a 40% decline in estimated glomerular filtration rate (eGFR) and end-stage kidney disease and rapid kidney function decline [RKFD, defined as annual eGFR decline of ≥ 5 ml/min/1.73m 2/yr] as the secondary outcome. For Non-CKD patients, an eGFR decline of ≥ 20%, incidence of CKD, and a declining slope of ≥3 ml/min/1.73m 2/yr were the outcomes. The association between UCaE and kidney function decline was assessed using Cox proportional hazards and generalized linear models. Results: The primary outcome was observed in 813 CKD and 109 without CKD over a median follow-up of 3.0 and 4.1 years, respectively. For CKD patients, every 1-mmol/d increase in UCaE was associated with a 15% decreased risk of CKD progression. The hazard ratio (HR) was 0.85, with a 95% confidence interval (CI) of 0.77-0.93. And, for Non-CKD patients, the risk of renal function decline decreased by 11%. The multivariate models indicated that there was an annual decrease of eGFR in both CKD and Non-CKD, with a reduction of 0.122 ml/min/1.73m2/yr (P < 0.001) and 0.046 ml/min/1.73m2/yr (P = 0.004), respectively, for every 1-mmol/d increase of UCaE. Conclusions: CKD experiences a decrease in 24-hour UCaE as early as stage 1, with a significant decline in stage 4. CKD and Non-CKD patients with lower UCaE levels are at an increased risk of renal decline, regardless of other variables.

Background Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-β1 (TGF-β1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. Methods Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRβ + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-β1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. Results An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-β1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-β1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. Conclusions The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

Considering the high prevalence and the lack of targeted pharmacological management of acute kidney injury (AKI), the search for new therapeutic approaches for it is in urgent demand. Mesenchymal stem cells (MSCs) have been increasingly recognized as a promising candidate for the treatment of AKI. However, clinical translation of MSCs-based therapies is hindered due to the poor retention and survival rates as well as the impaired paracrine ability of MSCs post-delivery. To address these issues, a series of strategies including local administration, three-dimensional culture, and preconditioning have been applied. Owing to the emergence and development of these novel biotechnologies, the effectiveness of MSCs in experimental AKI models is greatly improved. Here, we summarize the different approaches suggested to optimize the efficacy of MSCs therapy, aiming at promoting the therapeutic effects of MSCs on AKI patients.

Background Fabry disease is a rare hereditary disease involving multiple organs, and there are few reports on how the initial manifestations and renal involvement of these patients with classical and late-onset phenotype evolve with sexes and ages. To improve clinicians’ understanding of Fabry disease and avoid misdiagnoses by discussing the initial manifestations, first medical specialties visited and renal involvement development in patients. Methods This study collected relevant data from 311 Chinese Fabry disease patients (200 males, 111 females) and descriptive statistical analysis was used to analyze the evolution of the initial manifestations and renal involvement of patients with classical and late-onset phenotype at different sexes and ages. Results Regarding the age at manifestation onset, age at the first medical specialty visited and age at the diagnosis of Fabry disease, males were earlier than females, and males with classical phenotype were earlier than males with late-onset and females with classical phenotype. In both male and female patients, the initial manifestations of classical patients were mainly acroparesthesia, and the first medical specialty visited were mainly pediatrics and neurology. The initial manifestations of late-onset patients were mainly renal and cardiovascular involvement, and the first medical specialty visited were mainly nephrology and cardiology. In classical patients, both male and female, the initial manifestations of the preschool and the juvenile groups were mainly acroparesthesia, and the frequency of renal and cardiovascular involvement in the young group was higher than that in the preschool and juvenile groups. There was no obvious renal involvement in the preschool group, renal involvement was most common in the young group and the middle-aged and elderly group. Proteinuria can appear in classical male patients as early as approximately 20 years, and renal insufficiency can occur at approximately 25 years. With age, over 50% of classical male patients can develop varying degrees of proteinuria at the age of 25 and renal insufficiency at the age of 40. 15.94% of the patients progressed to dialysis or kidney transplantation, mainly classical males. Conclusions The initial manifestation of Fabry disease is affected by sex, age and classical/late-onset phenotype. The initial manifestations were mainly acroparesthesia and the frequency and degree of renal involvement increased gradually with aging in classical male patients.

Supplementary Figure. The expression of cyclin D1 mRNA detected by using realtime RT-PCR assay in non-synchronized HepG2 cells or synchronized S phase HepG2 cells.

The Hepatitis B virus X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). It has been suggested that the transcriptional activation of cyclin D1 by HBx is implicated in the development of HCC. However, numerous studies have shown that overexpression of cyclin D1 alone is not sufficient to drive oncogenic transformation. Herein, we investigated whether HBx can stabilize cyclin D1 and induce cyclin D1 protein nuclear accumulation, and thereby accelerate hepatocarcinogenesis. The effects of HBx on cyclin D1 stabilization were assessed in cell-based transfection, Western blot, immunoprecipitation, immunocytofluorescence staining, and flow-cytometric assays. The results demonstrated that ectopic expression of HBx in HCC cells could extend the half-life of cyclin D1 protein from 40–60 minutes to 80–110 minutes. HBx stabilized cyclin D1 primarily in the S phase of the cell cycle, in a manner dependent on the inactivation of GSK-3β, which was mediated by ERK activation. HBx also prompted the nuclear accumulation of cyclin D1, and cotransfection of the constitutively active mutant of GSK-3β along with HBx could reverse the nuclear accumulation and subsequent cell proliferation induced by HBx. Further, a positive correlation between HBx and nuclear cyclin D1 level was established in HCC specimens detected by an immunohistochemical assay. Taken together, our results indicated that HBx could stabilize and increase cyclin D1 nuclear accumulation through ERK-mediated inactivation of GSK-3β. This HBx-induced cyclin D1 upregulation might play an important role in HCC development and progression. Cancer Prev Res; 8(5); 455–63. ©2015 AACR.

Supplementary Tables 1 and 2. Real-time RT-PCR primers and Antibodies used in this manuscript Table S1. Real-time RT-PCR primers; Table S2. Antibodies

Background Glomerular disease, including immunoglobulin A nephropathy (IgAN) and Henoch–Schönlein purpura nephritis, is one of the most common kidney diseases in children. The diagnosis of these diseases depends on pathological biopsy, although this procedure is seriously limited by its invasive and high-risk nature. Objective To investigate the potential of contrast-enhanced ultrasonography (CEUS) for evaluating the histopathological severity of IgAN and Henoch–Schönlein purpura nephritis (HSPN). Materials and methods We investigated a total of 13 children with IgAN and 12 children with HSPN confirmed by renal histopathology. We reevaluated the pathological lesions of the children according to the Oxford classification and the Lee grading system and then all the children underwent CEUS. Using SonoLiver software, we constructed time–intensity curves of CEUS for regions of interest in the renal cortex. We analyzed CEUS quantitative parameters for IgAN and HSPN and used Spearman correlation analysis to examine the correlation between CEUS parameters and clinicopathological indexes in the study cohort. Results The CEUS parameters rise time (RT) and time to peak (TTP) were significantly higher in children with Lee grade IV than in those with Lee grades II or III. Spearman correlation analysis revealed a positive correlation between rise time and time to peak with Lee grade in the overall cohort of children, and a positive correlation between rise time and time to peak and severity of crescents in the Oxford classification scoring system. Conclusion Contrast-enhanced US may be used as a noninvasive imaging technique to evaluate the severity of renal pathology and formation of crescents in children with IgAN and HSPN.

The molecular mechanisms underlying hepatocellular carcinoma (HCC) remain poorly understood. In this study, we investigated cell division cycle-associated 3 (CDCA3) expression status and characterized a CDCA3-related long non-coding RNA (lncRNA) in HCC.RT-qPCR and western blot were used to determine CDCA3 expression level in HCC clinical specimens. 5' and 3'-RACE, RNAscope, RNA pull-down, CRISPR/Cas9-based RNA immunoprecipitation (CRIP) and site-directed mutation experiments were used to characterize lncCDCA3L and investigate its function target. Chi-square test and Kaplan-Meier analysis were used to assess lncCDCA3L clinical significance. The effects of lncCDCA3L on HCC development were assessed by overexpression in vitro and in vivo.In this study, we found CDCA3 was a potential oncogenic factor in HCC and characterized the lncCDCA3L, which could inhibit CDCA3. LncCDCA3L is significantly downregulated in HCC and its expression level is associated with tumour size and can act as an independent risk factor affecting postoperative survival time in HCC patients. Mechanistically, lncCDCA3L can repress CDCA3 protein level and inhibit hepatocarcinogenesis by directly binding to CDCA3 mRNA at 1423-1455 region via a novel manner based on a hairpin structure motif.Our study collectively unveiled the molecular mechanisms of how lncCDCA3L repressed the tumourigenic properties of HCC cells and exhibited a tumour suppressor character in HCC in a CDCA3-dependent manner. The findings here support lncCDCA3L can be used as a candidate prognostic biomarker for HCC patients.

The AU-rich binding factor 1 (AUF1) is one of the well known adenylate-uridylate-rich element (ARE)-specific RNA-binding proteins (ARE-BPs) for which dysregulation has been reported in various human cancers. However, the involvement of AUF1 in the initiation and progression of hepatocellular carcinoma (HCC) is still elusive. In this study, we aimed at exploring the clinical significance, function, and mechanism of the abnormal expression of AUF1 in HCC. Using a bioinformatics analysis of The Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI) database, we identified that AUF1 was abnormally highly expressed in HCC tissues and that the high expression of AUF1 was correlated with poor prognosis in patients with HCC. We also confirmed the increased AUF1 expression and its prognostic value in our HBV-related HCC cohorts. AUF1 overexpression in hepatoma cells promoted cell proliferation and increased the resistance of hepatoma cells toward doxorubicin, whereas knockdown of AUF1 exerted the opposite effects. Mechanistically, we demonstrated that AKR1B10 was a critical target of AUF1 and was essential for sustaining the AUF1-induced proliferation and drug resistance of hepatoma cells. AUF1 increased AKR1B10 expression by binding to the 3'UTR region of AKR1B10 mRNA and stabilizing AKR1B10 mRNA. Additionally, we demonstrated that E2F1 enhanced AUF1 expression in HCC at the transcription level. Our study revealed a novel role of AUF1 in promoting the development and drug resistance of HCC via the post-transcriptional regulation of AKR1B10 expression. The E2F1/AUF1/AKR1B10 axis can serve as a potential therapeutic target in HCC.

Kidney fibrosis is considered the final convergent pathway for progressive chronic kidney diseases, but there is still a paucity of success in clinical application for effective therapy. We recently demonstrated that the expression of secreted leucine-rich α-2 glycoprotein-1 (LRG1) is associated with worsened kidney outcomes in patients with type 2 diabetes and that LRG1 enhances endothelial transforming growth factor-β signaling to promote diabetic kidney disease progression. While the increased expression of LRG1 was most prominent in the glomerular endothelial cells in diabetic kidneys, its increase was also observed in the tubulointerstitial compartment. Here, we explored the potential role of LRG1 in kidney epithelial cells and TGF-β-mediated tubulointerstitial fibrosis independent of diabetes. LRG1 expression was induced by tumor necrosis factor-α in cultured kidney epithelial cells and potentiated TGF-β/Smad3 signal transduction. Global Lrg1 loss in mice led to marked attenuation of tubulointerstitial fibrosis in models of unilateral ureteral obstruction and aristolochic acid fibrosis associated with concomitant decreases in Smad3 phosphorylation in tubule epithelial cells. In mice with kidney epithelial cell-specific LRG1 overexpression, while no significant phenotypes were observed at baseline, marked exacerbation of tubulointerstitial fibrosis was observed in the obstructed kidneys. This was associated with enhanced Smad3 phosphorylation in both kidney epithelial cells and α-smooth muscle actin-positive interstitial cells. Co-culture of kidney epithelial cells with primary kidney fibroblasts confirmed the potentiation of TGF-β-1mediated Smad3 activation in kidney fibroblasts through epithelial-derived LRG1. Thus, our results indicate that enhanced LRG1 expression induced epithelial injury is an amplifier of TGF-β signaling in autocrine and paracrine manners promoting tubulointerstitial fibrosis. Hence, therapeutic targeting of LRG1 may be an effective means to curtail kidney fibrosis progression in chronic kidney disease.

Introduction: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient’s quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. Methods: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (β2M) and parathyroid hormone (PTH) were measured at baseline, 3–6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of β2M and PTH, while the secondary outcome was the reduction of the pruritus score. Results: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of β2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. Conclusion: The long-term HP + HD can reduce β2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Background: IgA nephropathy is the most common primary glomerular disease and an important cause of chronic kidney disease. Previous clinical studies have confirmed that Huangkui capsule could reduce urine protein of IgA nephropathy by 100 mg/d losartan potassium. However,the effect of Huangkui capsule on IgA nephropathy is not clear. Methods: Based on two multicenter, large sample phase IV clinical trials (NCT 02231125; NCT 02231138), eligible IgA nephropathy patients were screened and the related data were extracted for secondary analysis. Patients were grouped according to the baseline urinary protein, glomerular filtration rate, or pathologic characteristics using IgA nephropathy Oxford classification and the curative effect was analyzed. Taking the decrease of urine protein ≥30% after Huangkui capsule 6-month treatment as the effective standard, multiple regression analysis was used to analyze the influencing factors of Huangkui capsule in reducing urinary protein in IgA nephropathy patients. Results: 503 patients with IgA nephropathy were enrolled. The efficacy of Huangkui capsule in reducing urinary protein in patients with baseline 24h urinary protein ≥1.0 g/d or glomerular filtration rate ≥60 ml/min reach the effective standard. 24h baseline urinary protein, body mass index, serum albumin, and serum creatinine were the independent influencing factors of Huangkui capsule in reducing urinary protein, but there was no significant correlation with the baseline pathological characteristics. After 6 months of Huangkui capsule treatment, the decrease rate of urine protein increased by 7.9% for every 100mg increase of 24h urinary protein and 6.7% for every 1g/L increase of ALB, while decreased by 1.1% and 7% respectively, for every 1μmmol/L increase of serum creatinine and 1kg/m2 increase of body mass index. Conclusion: The effect of Huangkui capsule is influenced by basic urinary protein, body mass index, serum albumin, and serum creatinine in IgA nephropathy patients. Huangkui capsule can effectively reduce urinary protein in patients with baseline urinary protein ≥1.0 g/d or glomerular filtration rate ≥60 ml/min.

Introduction: Youthful blood environment was shown to decelerate the aging process of kidney and to attenuate senile renal fibrosis in a young-old parabiotic animal model; in addition, we identified a stem cell factor (SCF) that is closely linked with the process. This research was to investigate the effect of youthful blood environment on senile renal interstitial fibrosis and the role of SCF. Methods: We bred SCF receptor c-Kit gene loss-of-function Wps/Wps mice and established a combination mice model that was subjected to unilateral ureteral obstructive (UUO) and parabiotic surgeries. Parabiotic mice were divided into isochronic parabiotic (young-young, Y-IP and old-old, O-IP) and heterochronic parabiotic (young-old, HP) groups. UUO surgery was performed in one of the parabiotic pairs in the IP group (Y-IPuuo and O-IPuuo) and in the elderly mice in the HP group (O-HPuuo). In order to study the role of SCF/c-kit on renal interstitial fibrosis, UUO surgery was performed in wildtype (WT) and Wps/Wps mice. Results: Fourteen days after UUO surgery, the kidney interstitial fibrosis area, kidney function, and the expressions of SCF/c-Kit, pNF-κB, and fibrosis-related proteins in the O-HPuuo group were significantly lower than those in the Ouuo and O-IPuuo groups. Compared with wildtype UUO mice, the expressions of pNF-κB and fibrosis-related proteins, and the kidney function were all significantly decreased in Wps/Wps UUO mice. Conclusion: Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice, and ameliorated UUO-induced kidney fibrosis and function loss.

Rationale and Objectives This study aims to evaluate the diagnostic accuracy, inter-reader, and intra-reader variability of the ACR Thyroid Imaging Reporting and Data System (TI-RADS) for risk-stratification of indeterminate thyroid nodules using next generation genetic sequencing and tissue histology as a reference standard. Materials and Methods Retrospective chart review was performed on all patients who underwent thyroid ultrasound for a nodule with subsequent fine-needle aspiration ± surgical resection from January 2017 to August 2018. Four radiologists with expertise in thyroid ultrasound assessed imaging twice, ≥1 month apart. Results of cytology and next generation genetic sequencing were used as a reference standard for high versus low risk of malignancy in each nodule. Inter-reader reliability between readers and intra-reader reliability between replicate self-reads for TI-RADS categorization were assessed. Univariate analysis, kappa statistics, and receiver operating characteristic curve were calculated. Results One hundred and thirty six nodules across 121 patients met inclusion criteria. 84.6% of patients were female and average age was 55.8 ± 14.1 years. One hundred and eighteen of 135 nodules (87%) had indeterminate cytology (Bethesda III or IV). One of 23 high-risk mutations was identified in 30.1% (42) of the nodules. Of the 52 patients who had surgery, 24 (47.1%) had confirmed malignant disease on surgical pathology. Inter-reader reliability between the four radiologists was marginal, κ = 0.293. Intra-reader reliability ranged from marginal to good, κ = 0.337 to κ = 0.560, respectively. The area under the receiver operating characteristic curve was 0.509, and no optimal TI-RADS Level for identifying high-risk nodules existed. Conclusion The ACR TI-RADS classification system performs with low inter-reader and intra-reader reliability when assessing the genetic risk of nodules with indeterminate cytology.

The present study aims to investigate the impact of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia. Thirty Sprague-Dawley rats were randomly divided into five groups, including normal diet group, and diabetes model (DM) group, DM + metformin treatment (DMM) group, DMM + hypoxia treatment (DMMH) group and DMMH + hydrogen-rich water (DMMHR) group. We found that the levels of lactic acid, pyruvate and lactate dehydrogenase were significantly lower in the blood of DMMHR group than DMMH group. Superoxide dismutase and glutathione levels in liver and heart were significantly higher in DMMH group after hydrogen-rich water treatment, while malondialdehyde and oxidized glutathione levels were decreased in DMMHR group when compared with DMMH group, which indicates that hydrogen-rich water could reduce oxidative stress. qPCR analysis demonstrated that that pro-apoptotic genes Bax/Caspase-3 were upregulated in DM group and metformin treatment suppressed their upregulation (DMM group). However, hypoxic condition reversed the effect of metformin on apoptotic gene expression, and hydrogen-rich water showed little effect on these genes under hypoxia. HE staining showed that hydrogen-rich water prevented myocardial fiber damages under hypoxia. In summary, we conclude that hydrogen-rich water could prevent lactate accumulation and reduce oxidant stress in diabetic rat model to prevent hypoxia-induced damages. It could be served as a potential agent for diabetes patients with metformin treatment to prevent lactic acidosis and reduce myocardial damages under hypoxic conditions.

Background: Anticoagulation-free continuous renal replacement therapy (CRRT) was recommended by the current clinical guideline for patients with increased bleeding risk and contraindications of citrate. Nevertheless, anticoagulation-free CRRT yielded heterogeneous filter lifespan. Furthermore, the specific cutoff values for traditional coagulation parameters to predict sufficient filter lifespan of anticoagulation-free CRRT have not yet been determined. The purpose of our present study was to develop and validate a model for predicting sufficient filter lifespan in anticoagulation-free CRRT patients. Methods: Patients who underwent anticoagulation-free CRRT in our center between June 2013 and June 2019 were retrospectively included. The primary outcome was sufficient filter lifespan (≥24 h). Thirty-seven predictors were included for modeling based on their clinical significance and previous reports. The final model was developed by using multivariable logistic regression analysis and was validated in a separate external cohort. Results: The development cohort included 170 patients. Sufficient filter lifespan was observed in 80 patients. Thirteen variables were independent predictors for sufficient filter lifespan by logistic regression: body temperature, mean arterial pressure, activated partial thromboplastin time, direct bilirubin, alkaline phosphatase, blood urea nitrogen, vasopressor use, body mass index, white blood cell, platelet count, D-dimer, uric acid, and pH. The area under the curve (AUC) of the stepwise model and internal validation model was 0.82 (95% confidence interval [CI] [0.76–0.88]) and 0.8 (95% CI [0.74–0.87]), respectively. The positive predictive value and the negative predictive value of the stepwise model were 0.77 and 0.79, respectively. The validation cohort included 44 eligible patients and the AUC of the external validation model was 0.82 (95% CI [0.69–0.96]). Conclusions: The use of a prediction model instead of an assessment based only on coagulation parameters could facilitate the identification of the patients with filter lifespan of ≥24 h when they accepted anticoagulation-free CRRT.

Aim: We performed a systematic review and network meta-analysis, evaluating the safety and efficacy of Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) among dialysis chronic kidney disease (CKD) patients. Methods: Safety was evaluated with any adverse events (AEs), serious adverse events (SAEs), and twelve common events. Efficacy was mainly analyzed with hemoglobin (Hb) response. All reported results were summarized using mean difference (MD) and risk ratio (RR) with 95% confidence interval (CI). Publication bias was assessed through funnel plots. Results: Twenty trials with 14,947 participants were included, comparing six HIF-PHIs with Erythropoiesis-stimulating agents (ESAs). No significant differences were indicated in AEs and SAEs between each HIF-PHI and ESA. The occurrence of gastrointestinal disorder was higher in Enarodustat and Roxadustat than in ESAs (RR: 6.92, 95% CI: 1.52-31.40, p=0.01; RR: 1.30, 95% CI: 1.04-1.61, P=0.02). The occurrence of hypertension was lower in Vadadustat than in ESAs (RR: 0.81, 95% CI: 0.69-0.96, p=0.01). The occurrence of vascular-access complications was higher in Roxadustat (RR: 1.15, 95% CI: 1.04-1.27, p＜0.01) while lower in Daprodustat (RR: 0.78, 95% CI: 0.66-0.92, p＜0.01) than in ESAs. In the risk of the other nine events, including cardiovascular events, no significant differences were observed between HIF-PHIs and ESAs. For efficacy, network meta-analysis showed that the overall performance was similar to ESAs. Conclusion: Although HIF-PHIs did not show significant differences from ESAs in terms of overall AEs and SAEs, statistical differences in gastrointestinal disorder, hypertension, and vascular-access complications were observed between HIF-PHIs, which deserved to be noted in clinical decision-making.

Thyroid cancer patients have a good prognosis, and their long survival increases the likelihood of developing a second primary tumor. Meanwhile, pancreatic cancer (PC) has a poor prognosis and therapeutic efficacy. However, the association between prior thyroid cancer and the subsequent PC prognosis is unknown. Herein, we selected pathologically diagnosed PC patients older than 17 between 2010 and 2015 from the SEER database. We used propensity score matching (PSM) to reduce confounding factors between groups and matched each PC patient witha history of thyroid cancerwith 10 PC patients without a history of thyroid cancer. Finally, we selected 103 PC patients with prior thyroid cancer and 1030 PC patients without prior thyroid cancer. Then, we analyzed the factors influencing the overall survival (OS) and the cancer-specific survival (CSS) of PC patients. The median overall survival of PC patients with and without a history of thyroid cancer was 12 and 9 months, respectively. The history of thyroid cancer in PC patients reduced the PC-specific mortality (p < 0.05). Prior thyroid cancer might increase PC patients’ survival and reduce PC-specific death, especially in male patients. Subject terms: Cancer

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, and its early pathogenesis is critical. Shear stress caused by glomerular hyperfiltration contributes to the initiation of kidney injury in diabetes. The primary cilium of renal tubular epithelial cells (RTECs) is an important mechanical force sensor of shear stress and regulates energy metabolism homeostasis in RTECs to ensure energy supply for reabsorption functions, but little is known about the alterations in the renal cilium number and length during the progression of DKD. Here, we demonstrate that aberrant ciliogenesis and dramatic increase in the cilium length, the number of ciliated cells, and the length of cilia are positively correlated with the DKD class in the kidney biopsies of DKD patients by super-resolution imaging and appropriate statical analysis methods. This finding was further confirmed in STZ-induced or db/db diabetic mice. These results suggest that the number and length of renal cilia may be clinically relevant indicators and that cilia will be attractive therapeutic targets for DKD.

Luteolin is a natural flavonoid exhibiting multiple pharmacological activities. Renal anaemia is an important complication of chronic kidney disease (CKD). Whether luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia remains unclear. We examined the therapeutic effects of luteolin in

Biological age (BA) may reflect the actual aging state in humans better than chronological age (CA). The study aimed to construct BA models suitable for the Chinese Han population by selecting appropriate aging markers and evaluation methods.A total of 1207 individuals (21∼91 years) from the Han Chinese population in Beijing were examined for essential organ functions, and 156 cardiovascular, pulmonary function, and atherosclerotic indices and clinical and genetic factors were used as candidate markers of aging. BA models were constructed using multiple linear regression (MLR), principal component analysis (PCA), and the Klemera and Doubal method (KDM). Models were internally and externally validated using cross-validation and disease populations.Nine aging markers were selected. Two MLR, three PCA, and three KDM models were successfully constructed. External validation showed that the difference between CA and BA was most significant in the PCA3 and KDM2 models, while there was no significant difference in the MLR1 and MLR2 models; the fitted lines for BA in the disease population were higher than those in the healthy population in the MLR1, MLR2, KDM1, and KDM2 models, while the other models showed the opposite.Based on a healthy population in Beijing, nine markers representing multiple organ/system functions were screened from the candidate markers, eight methods were successfully used to construct BA models, and the KDM2 model was found to potentially be more appropriate for assessing BA in the Chinese Han population.

With the development and introduction of immune checkpoint inhibitors (ICIs) in cancer patients, immune-related side effects have increasingly attracted attention. However, the risks of immune-related renal toxicity are poorly characterized. In this study, we performed a network meta-analysis (NMA) of ICI-related randomized clinical trials (RCTs) to elucidate the comparative risk of acute kidney injury (AKI) in cancer patients receiving different ICIs. We also sought to identify other factors potentially affecting the risk of AKI. PubMed and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May 2021. Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data. We performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment groups. We also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct meta-analysis. Once significant heterogeneity was detected in a traditional direct meta-analysis, multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI. A total of 85 RCTs were included in this study. In the NMA for the risk of grade 1-5 and 3-5 AKI, ipilimumab showed a significantly higher risk than avelumab and durvalumab, whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab (N1I3) showed a significantly higher risk than other groups. In terms of treatment ranking, durvalumab ± low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI, whereas N1I3, ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 AKI. Compared with other cancers, renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI. The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy. In this NMA involving large-scale up-to-date ICI trials, we demonstrated the comparative safety of existing ICI drugs for grade 1-5 and grade 3-5 AKI. Based on data from the ICI arms of these trials, we also revealed several potential risk factors for immune-related AKI, including tumor type and treatment paradigm.

As the most frequent inherited tubulopathy, Gitelman syndrome (GS), has an incidence that has increased worldwide. The distribution of SLC12A3 gene mutation hotspots deserves exploration. In addition, GS is not a benign syndrome; however, the diagnostic process of GS has not yet been completely detailed. Materials and methods We report two cases of GS pedigrees involving two previously unreported mutations, c. 676G>A, p. A226T and c. 421G>A, p. G141R, in the SLC12A3 gene and reviewed relevant literature. We searched the literature for nucleotide of SLC12A3 in PubMed and other databases as of April 20, 2020. Results A total of 1,794 detected mutated alleles in 939 patients worldwide were included in this study. Splicing mutations and p. Gly741Arg were mutation hotspots in a European population. P. Leu858His and p. Thr60Met were mutation hotspots in an Asian population. P. Leu858His and p. Thr180Lys were considered mutation hotspots in the Japanese population, while p. Thr60Met and p. Asp486Asn were considered mutation hotspots in the Chinese population. Conclusion Our results identified two novel mutation sites (c. 676G>A, p. A226T and c. 421G>A, p. G141R), if their pathogenicity was determined this could contribute to the enrichment of database resources on GS. Our study has compiled the most comprehensive SLC12A3 gene mutation database in the world thus far to reveal that different regions have different mutation hotspots in SLC12A3. Moreover, the establishment of a diagnostic process for GS has important implications for confirmed cases.

The relationship between transforming growth factor β superfamily members (GDF11 and BMP4) and bone metabolism remains controversial. The aim of this study was to investigate the association between serum GDF11 and BMP4 levels and lumbar spine bone mineral density (LBMD) in a cohort of postmenopausal Chinese women. This was a non-prospective cross-sectional study of 350 postmenopausal women with a mean age of 63.13 ± 8.66 years who came from Shenyang, China. LBMD was measured using dual-energy X-ray absorptiometry. Serum GDF11 and BMP4 concentrations were detected using a sandwich enzyme immunoassay kit. Pearson’s correlation analysis and regression analyses were carried out to investigate the relationships between LBMD and serum GDF11 and BMP4 levels. A linear association between LBMD and serum LgGDF11 concentration was observed after adjusting for numerous confounders (P = 0.018). In addition, the osteoporosis (OP) was inversely related to LgGDF11 and the odds ratios for postmenopausal women with lumbar OP in LgGDF11 quartile group 2, group 3, and group 4 were 0.46 (95% CI 0.23–0.90, P

BACKGROUND The purpose of the present systematic review was to evaluate the incidence, risk factors, and outcome of hyperbilirubinemia after cardiac surgery. METHODS The Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework was employed to develop the search strategy, and the findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Embase, and the Cochrane Library were systematically searched for studies that provided data on the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac surgery patients from January 1960 to May 2020. Publication bias was graphically explored through funnel plots, and the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the included studies. RESULTS Ten studies with 6,100 patients were included in our systematic review. The pooled incidence of hyperbilirubinemia was 23% [95% confidence interval (CI), 0.13-0.32]. Preoperative factors, including right atrial pressure [mean difference (MD), 4.65; 95% CI, 4.43-4.88], total bilirubin (TB) concentration (MD, 0.72; 95% CI, 0.65-0.79), alkaline phosphatase (MD, 27.38; 95% CI, 12.94-41.82), and alanine aminotransferase (MD, 12.02; 95% CI, 10.73-13.31), and intraoperative factors, including cardiopulmonary bypass (CPB) time (MD, 1.57; 95% CI, 0.52-2.63), aortic cross-clamping (ACC) time (MD, 11.82; 95% CI, 9.50-14.14), and the amount of blood transfused (MD, 3.77; 95% CI, 0.68-6.85), were the most robust risk factors for hyperbilirubinemia after cardiac surgery. Additionally, postoperative hyperbilirubinemia was associated with increased in-hospital mortality [odds ratio (OR), 9.9; 95% CI, 5.00-19.60, P

The primary cilium is a hair-like, microtubule-based organelle that is covered by the cell membrane and extends from the surface of most vertebrate cells. It detects and translates extracellular signals to direct various cellular signaling pathways to maintain homeostasis. It is mainly distributed in the proximal and distal tubules and collecting ducts in the kidney. Specific signaling transduction proteins localize to primary cilia. Defects in cilia structure and function lead to a class of diseases termed ciliopathies. The proper functioning of primary cilia is essential to kidney organogenesis and the maintenance of epithelial cell differentiation and proliferation. Persistent cilia dysfunction has a role in the early stages and progression of renal diseases, such as cystogenesis and acute tubular necrosis (ATN). In this review, we focus on the central role of cilia in kidney development and illustrate how defects in cilia are associated with renal disease progression.

To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95%CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly.PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

Systemic lupus erythematosus (SLE) is a chronic multifactorial autoimmune disease that affects many organs, including the kidney. Lupus nephritis (LN) is a common manifestation characterized by heterogeneous clinical and histopathological findings, and often associates with poor prognosis. The diagnosis and treatment of LN is challenging, depending largely on renal biopsy, and there is no reliable non-invasive LN biomarker. Up to now, the complete remission rate of LN is only 20%∼30% after receiving six months of standard treatment, which is far from satisfactory. Moreover, adverse reactions to immunosuppressants, especially glucocorticoids, further compromise the prognosis of LN. Biological reagents targetting autoimmune responses and inflammatory pathways, bring hope to the treatment of intractable lupus. The European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) and KDIGO (Kidney Disease: Improving Global Outcomes) have been working on and launched the recommendations for the management of LN. In this review, we update our knowledge in the pathogenesis, diagnosis, and management of LN and prospect for the future potential targets in the management of LN.

The authors have requested that this preprint be removed from Research Square.

Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases, including mesangial proliferative nephritis and diabetic nephropathies. Knowledge of MC responses to pathological stimuli is crucial to the understanding of these disease processes. We previously determined that Krϋppel‐like factor 15 (KLF15), a kidney‐enriched zinc‐finger transcription factor, was required for inhibition of MC proliferation. In the present study, we investigated the direct target gene and the underlying mechanism by which KLF15 regulated mesangial proliferation. First, we screened small ubiquitin‐related modifier 1 (SUMO1) as the direct transcriptional target of KLF15 and validated this finding with ChIP‐PCR and luciferase assays. Furthermore, we demonstrated that overexpressing KLF15 or SUMO1 enhanced the stability of P53, which blocked the cell cycle of human renal MCs (HRMCs) and therefore abolished cell proliferation. Conversely, knockdown of SUMO1 in HRMCs, even those overexpressed with KLF15, could not inhibit HRMC proliferation rates and increase SUMOylation of P53. Finally, the results showed that the levels of SUMOylated P53 in the kidney cortices of anti‐Thy 1 model rats were decreased during proliferation periods. These findings reveal the critical mechanism by which KLF15 targets SUMO1 to mediate the proliferation of MCs.

Diabetes mellitus is one of the most critical global health concerns, with a fast-growing prevalence. The incidence of diabetic vascular complications is also rapidly increasing, exacerbating the burden on individuals with diabetes and the consumption of public medical resources. Despite the overall improvements in the prevention, diagnosis, and treatment of diabetic microvascular complications in recent years, safe and effective alternative or adjunctive therapies are urgently needed. The mechanisms underlying diabetic vascular complications are complex, with hyperglycemia-induced oxidative stress and inflammation being the leading causes. Therefore, glycemic control, antioxidation, and anti-inflammation are considered the main targets for the treatment of diabetes and its vascular comorbidities. Vaccinium L. (Ericaceae) is a genus of plants enriched with polyphenolic compounds in their leaves and fruits. Vaccinium and its extracts have demonstrated good bioactivity in reducing blood glucose, oxidative stress, and inflammation, making them excellent candidates for the management of diabetes and diabetic vascular complications. Here, we review recent preclinical and clinical studies on the potential effect of Vaccinium on ameliorating diabetes and diabetic complications, particularly diabetic kidney disease and diabetic retinopathy.

Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 mThe primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.NCT02063100 on ClinicalTrials.gov.

OBJECTIVE Severe acute kidney injury (AKI) and hyperbilirubinemia increase the morbidity and mortality risk in patients undergoing emergency surgery for acute type A aortic dissection (AAAD). Our purpose was to investigate the risk factors of mortality in AAAD surgery patients who had severe postoperative hyperbilirubinemia and AKI receiving continuous renal replacement therapy (CRRT). METHODS Patients who had severe hyperbilirubinemia and received CRRT after AAAD surgery in our center between January 2015 and December 2018 were retrospectively screened. Univariate and multivariate analyses were performed to identify the risk factors of in-hospital mortality. Kaplan-Meier curves were employed to evaluate the accumulated patient survival proportion. RESULTS After screening, 50 patients were included in our present study. The in-hospital mortality was 84%. The univariate logistic analysis showed that preoperative MAP (p = .017) and peak total bilirubin concentration (p