Objectives:Little is known about autoimmune hepatitis (AIH) in Chinese children. The study aimed to explore the clinical characteristics and predictors of outcomes in the Chinese paediatric AIH cohort. Methods:A retrospective review of all paediatric AIH cases from 2015 to 2025 was conducted at a single centre in Beijing, China. Results:Of the 50 enrolled cases, 39 (78.0%) presented with type 1 AIH (consisting of 30 female children (60.0%); median age of 9.2 years). At presentation, 24 (48.0%) patients had cirrhosis, 11 (22.0%) had liver failure, and 10 (20.0%) had decompensated cirrhosis at presentation. Compared to type 1, children with type 2 were younger and had higher levels of serum alanine aminotransferase [270.0 (166.0, 599.0) U/L vs. 610.0 (510.0, 1231.0) U/L, p = 0.003] and aspartate aminotransferase [335.0 (172.0, 756.0) U/L vs. 576.0 (433.0, 1020.0) U/L, p = 0.013]; however, there was no statistical significance in the outcome between the two groups (p > 0.05). In 48 cases that received initial immunosuppressive treatment (glucocorticoid alone = 18, in combination with azathioprine = 20, or with mycophenolate mofetil = 10), 41 (85.4%) patients survived with a native liver, and there was no statistical difference in prognosis among the three types of immunosuppressive treatments. Serum albumin levels and decompensated cirrhosis at presentation were identified as independent factors influencing the likelihood of death or the need for liver transplantation (OR 0.814 [95% CI 0.670-0.989], p = 0.039; OR 0.146 [95% CI 0.022-0.963], p = 0.046). Conclusion:The majority of paediatric AIH patients survive with a native liver, and the outcome is not related to the type of immunosuppressive therapies but to decompensated cirrhosis at presentation.

ABSTRACT Objective To investigate the longitudinal pathological changes in the spectrum of biopsy‐proven renal diseases among elderly patients over the past 20 years at a single center in China. Methods We retrospectively enrolled patients aged ≥ 60 years who underwent renal biopsy at Beijing Hospital between January 2005 and December 2024. Patients were stratified into four 5‐year periods (2005–2009, 2010–2014, 2015–2019, and 2020–2024) based on biopsy date. The frequency and distribution of biopsy‐proven renal diseases across these periods were analyzed. Results A total of 594 elderly patients were included, accounting for 29.2% of all native biopsies in our cohort. The mean age was 67.9 ± 5.7 years, with a male‐to‐female ratio of 1.4:1. The proportion of elderly patients undergoing renal biopsy increased significantly across the four periods (19.1%, 22.5%, 33.9%, 38.9%; χ2 = 60.160, p < 0.01). Nephrotic syndrome (NS) was the most common indication for biopsy, although its proportion declined over time. In contrast, the proportion of biopsies performed for chronic kidney disease (CKD) increased substantially. Primary glomerular nephropathy (PGN), secondary glomerular nephropathy (SGN), and tubulointerstitial nephropathy (TIN) accounted for 54%, 39.9%, and 6.1% of all cases, respectively. The most prevalent cause of PGN was membranous nephropathy (MN), and the leading pathological types of SGN included diabetic nephropathy (DN), antineutrophil cytoplasmic antibody‐associated vasculitis (AAV), and hypertensive nephropathy (HTN). Throughout the study period, the proportion of PGN decreased significantly (64.6%, 64.9%, 54.1%, 42.6%; χ2 = 18.5, p < 0.001), driven by a decline in MN (34.1%, 39.6%, 32.6%, 23%; χ2 = 10.015, p = 0.018). Conversely, the proportion of SGN increased markedly (29.3%, 32.4%, 39.4%, and 49.2%; χ2 = 13.0, p = 0.004), primarily due to rising trends in DN and HTN. Notably, during the period 2020–2024, SGN surpassed PGN as the predominant form of biopsy‐proven renal diseases among elderly individuals. Conclusions The utilization of renal biopsy in elderly patients has increased significantly over the past two decades. While NS remains the most common indication, a notable rise in biopsies for CKD has been observed. The pathological spectrum has undergone a significant shift, characterized by a dramatic decrease in PGN (especially MN) and a continuous increase in SGN (predominantly DN and HTN). The predominance shifted to SGN over PGN in biopsy‐proven renal diseases among the elderly in the most recent period.

Background Recent studies have indicated that patients with chronic kidney disease (CKD) experience central hypothyroidism (CH) following treatment with roxadustat. Our objective is to assess the effect of roxadustat on the hypothalamic-pituitary-thyroid (HPT) axis in patients undergoing maintenance hemodialysis (MHD) and to explore whether it may cause potential tissue toxicity. Methods A total of 140 patients undergoing MHD were enrolled in this cross-sectional study. Thyroid hormones, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), as well as parameters of lipid metabolism, cardiac function, and bone metabolism, were assessed. The patients were divided into two groups based on their roxadustat treatment status: the roxadustat group (n = 53) and the control group (n = 87), differences between groups were evaluated using the Student’s t-test or the Mann-Whitney U test. Unconditional logistic regression analysis was utilized to identify risk factors for hypothyroidism. Results The roxadustat group demonstrated lower serum levels of TSH, FT3, and FT4 compared to the control group. Additionally, four cases (7.5%) exhibited abnormalities in all three indicators, and seven cases had TSH levels below 0.4 mU/L. Notably, none of the patients exhibited clinical symptoms of hypothyroidism. Unconditional logistic regression analysis indicated that roxadustat was an independent risk factor for hypothyroidism, with an odds ratio (95% confidence interval) of 3.635 (1.593, 8.291). Furthermore, the roxadustat group had lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and higher levels of serum total procollagen type I N-terminal propeptide (TPINP). Conclusions Roxadustat is an independent risk factor for hypothyroidism; however, no adverse off-target effects on organs were observed.

BACKGROUND:Functional cure (FC) of chronic hepatitis B (CHB) is closely associated with restoration of HBV-specific humoural immunity, yet the epitope-resolved features of humoural immunity recovery during interferon-induced FC remain unknown. METHODS:We profiled HBV-specific humoural responses in 65 patients with CHB drawn from three independent PEG-IFNα-treated cohorts, including nucleos(t)ide analogue-treated patients with viral suppression and inactive HBsAg carriers. Linear epitope mapping was performed using phage immunoprecipitation sequencing (PhIP-seq), with key findings validated by longitudinal ELISA and complemented by ex vivo phenotypic characterisation of epitope-specific B cells using fluorescent peptide tetramers. FINDINGS:PhIP-seq identified 297 reactive peptides, with a marked enrichment of antibody reactivity toward the HBsAg preS domain in patients who achieved FC. Longitudinal analysis demonstrated that preS2-directed antibodies, particularly those targeting the N-terminal amino acids 1-26 (preS2 aa1-26), increased progressively and closely parallelled HBsAb seroconversion, consistently distinguishing FC from non-FC group. In parallel, ex vivo B-cell profiling revealed that preS2 aa1-26-specific B cells exhibited a plasmablast-skewed and IgG-dominant profile, in contrast to the more IgM-biased and less differentiated phenotypes observed in preS1- and SHBs-specific B cells. Within the preS2-specific compartment, FC showed higher CXCR5 and CD69 expression than non-FC group, indicative of enhanced maturation and improved follicular homing potential. INTERPRETATION:PreS2 aa1-26 may serve as a key humoural HBV-specific epitope associated with functional cure, with potential implications for immunotherapeutic strategies in CHB. FUNDING:This work was supported by the National Science and Technology Major Project (2025ZD01905905), National Key Research and Development Program of China (2022YFA1303600 and 2023YFC2308100), and the National Natural Science Foundation of China (82130019 and 82272311).

We aimed to evaluate the application value of multiparametric diffusion weighted magnetic resonance imaging (MRI) for the assessment and risk stratification of renal histopathological injuries in patients with IgA nephropathy (IgAN), as an exploratory study. 95 patients were prospectively enrolled, intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) were performed, and a renal biopsy was performed within 3 days after MRI examination. Finally, 31 patients with pathologically confirmed IgAN were selected for analysis, and glomerulosclerosis index (GSI) and tubulointerstitial fibrosis index (TBI) were assessed by two experienced pathologists who were blinded to the clinical and multiparametric diffusion weighted imaging MRI data. Correlation analysis showed that eGFR was negatively correlated with age, GSI, and TBI. Both GSI and TBI were negatively correlated with the true diffusion coefficient (D, cortex), mean diffusivity (MD, cortex and medulla), fractional anisotropy (FA, medulla), and axial diffusivity (Da, cortex and medulla), and positively correlated with the mean kurtosis (MK, cortex) and axial kurtosis (Ka, cortex and medulla). Compared with the normal control group, the moderate-to-severe GSI/TBI groups showed significant decreases in most diffusion parameters and increases in kurtosis parameters, while there was no significant difference in all MRI parameters between the mild injury groups and the control group. Multivariate regression and model validation showed that medullary FA was the independent imaging predictor of moderate-to-severe GSI in the DTI-based model (p = 0.013), and the clinical+DTI combined model had a high diagnostic efficacy (AUC = 0.932, optimism-corrected AUC = 0.858); eGFR was the only significant predictor in the DKI-based model (p = 0.023), with the clinical+DKI combined model AUC reaching 0.891 (optimism-corrected AUC = 0.801). As a preliminary exploratory study,DTI and DKI may provide useful non-invasive information for assessing renal histopathological alterations in IgAN patients. Medullary FA is a promising imaging biomarker for glomerulosclerosis, and its combination with clinical variables shows potential for identifying patients with moderate-to-severe disease. The originally hypothesized superiority of DKI-derived MK was not clearly demonstrated. These findings warrant further validation in larger cohorts. This study was registered at the Chinese Clinical Trial registry with the registration number was ChiCTR1800020390.

INTRODUCTION Renal impairment (RI) is a frequent complication in newly diagnosed multiple myeloma (NDMM). Recovery of renal function is associated with prolonged survival for NDMM. Daratumumab, a monoclonal antibody targeting CD38, is highly effective for both relapsed or refractory MM and NDMM. While daratumumab demonstrates remarkable efficacy for MM with RI in clinical trials, its impact on renal responses in the first-line setting is not as well described. AIM To evaluate the renal and hematologic response of daratumumab-based therapy as first-line treatment in NDMM with RI in this retrospective, multi-center study. METHOD A database search was conducted to identify patients who received daratumumab-based therapy after inpatient admission between December 2018 and March 2025. Included in the analysis were adult patients with newly diagnosed MM who met all the following criteria: presenting with RI (sCr ≥177 μmol/L and/or eGFR <40 mL/min/1.73 m2 by CKD-EPI). And RI was caused by MM cast nephropathy and confirmed by biopsy or clinical judgement. We assessed renal and MM disease response according to the International Myeloma Working Group (IMWG) criteria. Follow up was determined by reverse KM method. Progression-free and overall survival were calculated from the date of the first dose of daratumumab. RESULTS Between Jan 01,2019 and Mar 07,2025, 140 patients were identified across 22 centers, with a median age of 65 years (range: 34-92). Of the 126 patients with available FISH cytogenetic data, 78 (61.9%) patients were defined as R-ISS III and 29 (23.0%) patients had high-risk cytogenetic abnormalities [t(4;14), t(14;16), or del(17p)]. Median serum creatine level and eGFR were 332.8μmol/L (range: 130.7-1341.0) and 14.8 ml/min (range: 2.5-39.8), respectively. There were 28/140 (20.0%) patients requiring dialysis at diagnosis. The daratumumab-based regimens included dara-Vd in 71 patients (50.7%), dara-Rd in 12 patients (8.5%), dara-VRd in 17 patients (12.1%), dara-VPD in 16 patients (11.4%) and other daratumumab-based regimens in 17.1% patients. Thirty-six patients (25.7%) underwent first-line ASCT. The renal ORR at 3 months was 76.4% (including 13.6% renal PR, and 28.6% renal CR). The best renal ORR was 87.9% (20.7% renal PR, 36.4% renal CR). The 3-month hematological ORR was 93.6% (131/140), with 95 of 140 patients (67.9%) achieving at least very good partial response (VGPR) and 34 (24.3%) achieving CR or stringent CR. The best ORR was 93.6% (131/140), among which 77.1% achieved at least VGPR and 47.9% achieved CR/stringent CR. With a median follow up of 13.3 months, the estimated median progression-free survival (PFS) was 29.8 (95% CI 21.9-37.7) months, whereas median overall survival (OS) has not been reached. CONCLUSION Daratumumab combinations in first-line therapy are very effective for NDMM patients with RI.

Background and aims Esophagogastric varices (EGV) are common complications of primary biliary cholangitis (PBC). We examined the risk factors for variceal bleeding-related liver transplantation (LT) or death. Methods This prospective observational cohort study involved PBC in our hospital from 1 January 2005 to 1 January 2020. The clinical endpoints were variceal bleeding-related LT and death. Survival analysis was performed using the Kaplan–Meier estimate, cox regression analysis was performed to investigate risk factors. Results PBC with EGV had significantly shorter survival than those without (p = 0.002). Endoscopic prophylaxis significantly improved poor outcomes in PBC with EGV (p < 0.001). Risk factors in patients with EGV included: cholinesterase (CHE) of <1.0 × upper limit of normal (ULN), international normalized ratio (INR) of >1.2 × ULN at baseline, total bilirubin of >1.2 × ULN, aspartate aminotransferase (AST) of >2.3 × ULN after 1 year of ursodeoxycholic acid (UDCA) treatment, non-biochemical responders according to the Paris criteria, and no history of endoscopic therapy. In PBC without EGV, risk factors included AST of >2.3 × ULN, INR of >1.2 × ULN at baseline, CHE of <1.0 × ULN after 1 year of UDCA treatment, and GLOBE score of >1.125. Conclusion This study provides evidence that AST, INR and CHE are major risk factors for variceal bleeding-related poor outcomes in PBC. For PBC with EGV, a good biochemical response to UDCA and endoscopic prophylaxis may improve survival. These findings can aid for guiding initial PBC risk stratification and screening endoscopy in patients without EGV.

Low-molecular-weight heparin (LMWH) is an anticoagulant used to prevent clotting during blood purification treatments. This study aimed to evaluate the clinical use of the anti-factor Xa level (anti-Xa) for monitoring LMWH anticoagulant levels during intermittent venovenous hemofiltration (IVVHF). This prospective observational study enrolled patients who required IVVHF for renal failure in Beijing Hospital between May 2019 and February 2021. The LMWH anticoagulation was assessed by the coagulation grade of the filter and line. One hundred and ten participants were included. There were 90 patients with a filter and line coagulation grade of ≤ 1 and 20 patients with grade > 1. The anti-Xa level of 0.2 IU/mL was a critical value. The multivariable logistic regression analysis showed that anti-Xa level > 0.2 IU/mL (odd ratio [OR] = 2.263; 95% CI: 1.290–4.871, P = 0.034) and cardiovascular disease (OR = 10.028; 95% CI: 1.204–83.488; P = 0.033) were independently associated with the coagulation grade of the filter and line. Anti-Xa level could monitor LMWH anticoagulation during IVVHF.

Purpose. Metagenomics has revealed that, in addition to the digestive tract, certain viruses are also commonly found in human blood. In order to explore and monitor potential novel viruses, three serum samples of patients with chronic lymphocytic leukemia were collected at the No. 2 People’s Hospital of Changshu City, China. Materials and Methods. We sequenced the virome of serum samples from three patients with chronic lymphocytic leukemia using an unbiased viral metagenomic approach and subsequently performed maximum likelihood phylogenetic analysis using MrBayes v3.2. In addition, pairwise sequence comparison was produced with ORF1 amino acid sequences of anelloviruses within Bayesian consensus tree. Results. Partial genomes of eight different anelloviruses containing the complete ORF1 gene have been identified. BLASTp results showed that the amino acid sequence identity of these viruses with the best match in GenBank was between 56.22% and 95.43%. Phylogenetic analysis based on ORF1 indicated that seven sequences belong to the genus Alphatorquevirus and one sequence belongs to the genus Gammatorquevirus. Conclusions. This virological investigation has increased our understanding of the diversity of anelloviruses in human serum, but further study is needed to verify its potential correlation with disease.

Objective: To compare and analyze the clinical and chest computed tomography (CT) imaging features of COVID-19 patients with different disease courses. Methods: A retrospective analysis was performed for 161 cases with confirmed COVID-19 and positive chest CT lung infections from December 2022 to January 2023 at the fever clinic of Beijing Shijitan Hospital affiliated with Capital Medical University. The patients were divided into two groups based on the time of CT examination: <10 days and ≥10 days. We statistically analyzed the clinical manifestations and chest CT imaging characteristics of the two groups. Results: Of the 161 cases, 92 cases (57.1%) were in the <10-day group, and 69 cases (42.9%) were in the ≥10-day group. The clinical symptoms of the two groups showed that there was a statistical difference in the proportion of sore throat and myalgia between the two groups. Laboratory indicators showed that the C-reactive protein and lymphocyte count were significantly higher in the <10-day group. In terms of CT imaging features, the proportion of patients with perivascular, mixed distribution, large area, and air bronchogram was higher in the patients from the <10-day group, while the patients in the ≥10-day group had a significantly higher proportion of irregular boundaries, intralesional cord, reversed halo sign, pleural tail sign, subpleural line, and subpleural palisade. Conclusion: The clinical symptoms, laboratory indexes, and CT imaging features of COVID-19 pulmonary infection differed depending on the disease course, and exploring these differences can help clinicians diagnose and treat COVID-19 lung infections more effectively.

Background/aims Primary sclerosing cholangitis (PSC) is a chronic inflammatory biliary disease for which the immunopathological basis remains an enigma. Natural killer (NK) cells are key components of innate immunity and seemingly play diversified roles in different autoimmune disorders (AIDs). The aim of this study was to determine the role of NK cells in the pathogenesis of PSC. Methods The frequency and phenotype of circulating NK cells in a large cohort of patients with PSC and healthy controls (HCs) were systematically examined. In addition, the functional capacity of NK cells including cytotoxicity and cytokine production was studied. Results The frequency of CD3−CD56dimCD16+ (defined as CD56dim) NK cells in PSC patients was significantly lower in comparison to HCs. CD56dim NK cells from PSC displayed a more immature phenotype including high expression of the natural killing receptor NKp46 and downregulation of the highly differentiated NK cell marker CD57. Interestingly, the reduction of CD57 expression of NK cells was associated with the disease severity of PSC. In addition, PSC CD56dim NK cells exhibited increased CD107a degranulation and cytolytic activity toward target cells compared with HCs. Further analysis demonstrated that CD57−CD56dim NK cells from PSC had elevated expression of NKp46, NKp30, IL-2 receptor, and KLRG1 and higher cytotoxic capacity as compared to CD57+CD56dim NK cells. Conclusions Our data demonstrate that the differentiation of PSC NK cells is dysregulated with enhanced cytotoxic activity. This change is likely to be functionally involved in pathogenesis and disease progression, deducing the potential of NK-directed immunotherapy for PSC.

Background:Free light chains κ and λ (FLC κ, FLC λ) are of great significance in diagnostic and monitoring monoclonal gammopathy. Freelite and N-Latex methods are two common monitoring methods at present. But the two meanings are not completely equivalent, especially for patients with renal insufficiency. We analyzed the changes of serum and urine FLC in renal insufficiency patients without monoclonal gammopathy and the clinical significance of these changes.Methods:This study is an observational study. Patients ≥ 18 years old, who met the diagnostic criteria of chronic kidney disease (CKD), excluding monoclonal gammopathy, were selected. Fasting serum and 24-hour urine were taken to detect serum FLC κ, serum FLC λ, SCr, serum β 2-microglobulin, urinary FLC κ, urinary FLC λ, urinary α 1-microglobulin, and urinary β 2-microglobulin.Results:There was a good correlation between the two methods for determining serum/urinary FLC. No matter serum or urine, FLC showed a good correlation with renal function by the N-Latex method, but not by the Freelite method. Under the N-Latex method, FLC κ/λ remained stable, which was basically within the reference range of healthy people and was not affected by renal function. There was a good correlation between FLC detected by N-Latex and microglobulin in serum and urine.Conclusion:When the concentration of FLC is low, the N-Latex method is more recommended to monitor FLC. The FLC measured by the N-Latex method is more closely related to renal function. The ratio of FLC κ/λ determined by the N-Latex method remained stable within the recommended range.

BACKGROUND AND AIMS:Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease.APPROACH AND RESULTS:We conducted a case-control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta-analysis was performed to ascertain variants associated with AIH type 1. A single-nucleotide polymorphism within the human leukocyte antigen (HLA) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10-73 ). The meta-analysis also identified two non-HLA loci significantly associated with AIH: CD28/CTLA4/ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10-9 ) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10-9 ). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10-7 ), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10-7 ), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10-6 ), and LILRA4/LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10-6 ) had suggestive association signals with AIH.CONCLUSIONS:Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome-wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro-immune interaction in the pathogenesis of AIH.

Type 1 diabetes (T1D) is a complex disease and more than 100 genetic loci influencing T1D risk have been identified to date. Discovering the genes and biological mechanisms through which these variants impact T1D requires the integration of multiple data types. We have created the T1D Knowledge Portal (T1DKP; type1diabetesgenetics.org) to help researchers utilize genetic and functional genomic data to generate hypotheses about the genes involved in T1D and its complications. The T1DKP aggregates genetic association data from the T1D community along with relevant functional genomics (e.g., accessible chromatin, 3D conformation, gene expression, gene perturbation) data, which are loaded via a sister resource, the Common Metabolic Diseases Genome Atlas (cmdga.org) . Using the HuGeAMP software platform developed for the Common Metabolic Diseases Knowledge Portal (CMDKP; cmdkp.org) within the Accelerating Medicines Partnership for Common Metabolic Diseases, the T1DKP integrates data by applying bioinformatic methods such as meta-analysis of genetic association results to generate “bottom-line” p-values, enrichment of genetic association within tissue-specific genomic annotations, and more. Interactive visualizations allow the user to explore results and to perform custom, on-the-fly analyses. The T1DKP also includes expert-curated lists of predicted effector genes of T1D loci, displaying the supporting evidence behind each prediction. Since the T1DKP is nested within and built upon the same framework as the CMDKP, users may navigate seamlessly to see results relevant to other metabolic disorders. In total the T1DKP project aims to accelerate our understanding and treatment of T1D by providing decision support for researchers as they prioritize loci, variants, and genes for experimental study. Disclosure M.C.Costanzo: Other Relationship; Pfizer Inc. P.V.Kudtarkar: None. U.Nayak: None. S.Onengut-gumuscu: None. Y.Sun: None. S.S.Rich: None. J.Flannick: None. K.J.Gaulton: Consultant; Genentech, Inc., Stock/Shareholder; Neurocrine Biosciences, Inc., Vertex Pharmaceuticals Incorporated. N.Burtt: n/a. Funding National Institutes of Health (5UM1DK105554-07)

Abstract Background and aims The development of esophagogastric varices (EGV) is one of the most common complications in patients with Primary biliary cholangitis (PBC); yet, factors associated with their development have been poorly characterized. In this cohort, we aimed to investigate the clinical factors associated with EGV in patients with PBC. Methods: The cohort study included patients with PBC who received esophagogastroduodenoscopy screening and ursodeoxycholic acid (UDCA) therapy at baseline. Liver-related death and liver transplantation were assessed as the endpoint, liver transplantation-free survival rates were estimated by using Kaplan–Meier methods, and Cox regression analysis was performed to identify the potential risk factors of endpoint events for PBC with EGV. Results The 690 patients included in this study had a mean age of 57 years old and 553 (80.1%) were females, 13 (7.9%) in the 165 PBC with no liver cirrhosis and 400 (76.2%) in the 525 PBC with liver cirrhosis had signs of EGV, and 215 (31.2%) patients of the cohort had bleeding esophagogastric varices as the first presentation at diagnosis. The median (Interquartile range) follow-up period was 4.0 (2.0, 6.0) years. During the follow-up duration, 99 patients progressed to liver-related deaths, and 23 patients underwent liver transplantation. The 5-year cumulative LT-free survival was 88.20% (95% CI 83.7-92.7) in PBC without EGV, and 80.90% (95% CI 80.0-89.9), 80.30% (95% CI 69.7-90.9), 75.70% (95% CI 68.3-83.1) among PBC with small, medium and large-sized esophageal varices at baseline, respectively (p =0.002). The 10-year cumulative LT-free survival was 68.8% (95% CI 53.9-82.8) in PBC without EGV, and 54.2% (95% CI 36.4-72.0), 51.6% (95% CI 29.9-73.3), 62.1% (95% CI 49.2-75.0) among PBC patients with small, medium and large-sized esophageal varices at baseline, respectively (p=0.001). History of endoscopic therapy and UDCA biochemical responder with Paris criteria for PBC with EGV were associated with a statistically significant reduced risk of LT or death (p =0.001 and p=0.007).Conclusions Endoscopic therapy and a favorable biochemical profile of UDCA can prolong the LT-free survival of PBC patients with EGV, despite the presence of large-sized esophageal varices.

Primary biliary cholangitis (PBC) is an autoimmune liver disease, mainly characterized by chronic progressive cholestasis. The root cause of PBC is the loss of immune tolerance to autoantigen E2 subunit of pyruvate dehydrogenase (PDC-E2). The unique immunobiological characteristics of intrahepatic bile duct epithelial cells make it an active participant in the pathogenesis of PBC. In recent years, the detection rate of PBC has been increasing year by year, but the clinical situation of ursodeoxycholic acid monotherapy has not changed. Therefore, an in-depth understanding of the immune pathogenesis of PBC will help clinicians better prevent and treat diseases.

We investigated how age affected renal function in healthy subjects in Beijing and compared different estimated glomerular filtration rate (eGFR) equations. Kidney function was evaluated by five equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); the Chinese version of the MDRD (MDRDc); Full Age Spectrum (FAS); and Berlin Initiative Study (BIS). A total of 46,708 subjects were enrolled and followed-up for 3 years. All showed an increase in sCr and a reduction in eGFR with increasing age. Over the 3 years, the eGFR and serum creatinine (sCr) remained unchanged in most subjects. Different equations showed good consistency; the intraclass correlation coefficients (ICC) was 0.849 for males, and 0.817 for females. The CKD-EPI equation yielded higher GFR values than the other equations (according to sCr levels). For subjects aged over 70 years, the BIS equation produced the lowest eGFR values. In summary, we observed that the renal function of individuals was relatively stable with increasing age, although different eGFR equations yielded data that varied across different populations of subjects and sCr levels.

Objective:To compare the advantages and disadvantages of several formulas for estimated glomerular filtration rate (eGFR) based on serum creatinine in elderly patients with chronic kidney disease (CKD) over 60 years old.Methods:CKD patients aged≥60 years old in Beijing Hospital from January 2012 to October 2017 were selected as subjects. Measured glomerular filtration rate (mGFR) was detected by 99mTc-DTPA renal dynamic imaging and used as a reference standard. According to the mGFR value, the patients were divided into 4 groups: mGFR<30 ml·min -1·(1.73 m 2) -1 group, 30≤mGFR<45 ml·min -1·(1.73 m 2) -1 group, 45≤mGFR<60 ml·min -1·(1.73 m 2) -1 group and mGFR≥60 ml·min -1·(1.73 m 2) -1 group. The deviation of each formula was compared by Bland-Altman scatter chart, and the accuracy of each formula was evaluated by the proportion of eGFR within mGFR (1±30%) ( P30) and root mean square error ( RMSE). Wilcoxon paired rank sum test was used to compare the deviation of each formula, and McNemar test was used to compare the difference of P30 among these formulas. Results:A total of 628 patients with CKD were enrolled in this study. The median age was 76.0(71.0, 81.0) years old. The median serum creatinine and mGFR were 110.0(86.0, 152.0) μmol/L and 42.90(29.88, 55.68) ml·min -1·(1.73 m 2) -1, respectively. Each eGFR formula based on serum creatinine overestimated glomerular filtration rate in varying degrees. Among them, the accuracy of Berlin Initiative Study (BIS) formula and full age spectrum (FAS) formula was the best ( P30 were 68.3% and 68.0% respectively), followed by the Chinese race coefficient of Chronic Kidney Disease Epidemiology Collaboration (C-CKD-EPI) formula ( P30 was 65.4%). The accuracy of the other formulas was poor. In terms of deviation, C-CKD-EPI formula was the best (0.27). In the group of mGFR<30 ml·min -1·(1.73 m 2) -1, the accuracy of all formulas was poor, and the accuracy of FAS formula was slightly better than that of other formulas ( P30 was 51.0%). In the group of 30≤mGFR<45 ml·min -1·(1.73 m 2) -1, the deviation of C-CKD-EPI formula was the smallest (3.11). In terms of accuracy, BIS and FAS formulas were better than others, and the P30 were 64.6% and 63.0% respectively. In the group of 45≤mGFR<60 ml·min -1·(1.73 m 2) -1, the deviation of C-CKD-EPI formula was also the smallest (0.72), and the accuracy of BIS formula was the best ( P30 was 82.5%), followed by FAS formula ( P30 was 79.7%). In the group of mGFR≥60 ml·min -1·(1.73 m 2) -1, the deviation and accuracy of Xiangya formula were the best (the deviation and P30 were -0.53 and 96.5% respectively), and the P30 of BIS and C-CKD-EPI formulas were 87.6% and 87.6%, respectively. Conclusions:In the elderly patients with CKD over 60 years old, the accuracy of eGFR based on serum creatinine increases with the increase of mGFR. BIS and FAS formulas are recommended first. The accuracy of each formula is poor in patients with severe renal insufficiency.

Purpose Sclerostin is an antagonist of the Wnt/β-catenin pathway. We previously reported that sclerostin is closely related to carotid artery atherosclerosis and long-term outcome in hemodialysis patients. The present study investigated the association between sclerostin, renal function, and carotid artery atherosclerosis in non-dialysis patients with stage 3–5 chronic kidney disease (CKD 3–5ND). Methods A total of 140 patients with CKD 3–5ND were enrolled in this cross-sectional study. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate (eGFR). Atherosclerotic plaques in the carotid artery were detected by B-mode Doppler ultrasound. Blood samples were collected to assess serum sclerostin levels. Unconditional logistic regression analysis was used to identify risk factors for carotid atherosclerotic plaques. Results The median eGFR was 24.9 ml/min/1.73 m 2 (interquartile range [IQR] 10.0–40.3 ml/min/1.73 m 2 ) and median serum sclerostin level was 46.76 pmol/l (IQR 30.18–67.56 pmol/l). Carotid atherosclerotic plaques were detected in 104 subjects (74.3%). There was a negative association between sclerostin level and eGFR ( r = − 0.214, p = 0.011). Unconditional logistic regression analysis revealed that sclerostin level was an independent risk factor for the occurrence of carotid plaques, with an odds ratio (95% confidence interval) of 1.026 (1.003, 1.051). Conclusion Serum sclerostin increases with declining renal function in patients with CKD 3–5ND. Sclerostin is an independent risk factor for carotid atherosclerosis.

Glycosylation of antibodies, particularly in the Fc domain, critically modulate the ability of antibodies to bind to FcRs, maintaining immune quiescence to achieve a finely orchestrated immune response. The removal of sialic acid and galactose residues dramatically alters the physiological function of IgGs, and alterations of Ig glycosylation have been associated with several autoimmune disorders. However, Ig glycosylation has not been extensively studied in autoimmune cholangitis. We applied triple quadruple mass spectroscopy with subsequent multiple reaction monitoring to elucidate the profile, composition and linkage of sugar residues of antibody glycans in patients with primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and healthy controls (HC). Agalactosylated, HexNAc terminated IgG1 glycoforms were enriched in both PBC and PSC. Levels of IgM glycans at site N439 and fucosylated glycans in J chain, were significantly decreased in PBC compared to PSC and HC. PSC patients had decreased bisecting glycoforms and increased biantennary glycoforms on IgA compared to PBC. Importantly, our data demonstrate the association of distinct branching and composition patterns of Ig glycoforms with disease severity and liver cirrhosis, which highlight the importance of glycan biology as a potential mechanism and/or a disease specific signal of inflammation.