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"Wan, Qijun"
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Non-linear relationship between the body roundness index and incident type 2 diabetes in Japan: a secondary retrospective analysis
by
Wan, Qijun
,
Wu, Liling
,
Hu, Haofei
in
Biomedical and Life Sciences
,
Biomedicine
,
Body roundness index
2022
Background
Body roundness index (BRI) is one of the obesity-related anthropometric indices. However, studies on the relationship between BRI and diabetes risk is limited. The purpose of this study was to explore the relationship between baseline BRI and incident type 2 diabetes mellitus (T2DM) in the Japanese population.
Methods
A retrospective longitudinal study of 15,310 participants in a physical examination program at Murakami Memorial Hospital in Japan from 2004 to 2015. The association between BRI levels and incident T2DM was analyzed by Cox proportional-hazards regression, smooth curve fitting, subgroup analyses, and a set of sensitivity analyses. Receiver operating characteristic curve analysis was used to assess the ability of BRI to predict diabetes.
Result
Baseline BRI levels were elevated in participants who developed T2DM. Baseline BRI levels were positively associated with incident T2DM after adjusting confounding variables (HR = 1.570, 95% CI 1.360–1.811). Additionally, we did a set of sensitivity analyses to ensure the robustness of the results. There was also a non-linear relationship between BRI and incident diabetes in both genders, and the inflection point of BRI was 4.137 in females and 3.146 in males. We found a strong positive correlation between BRI and the incidence of diabetes on the right of the inflection point (Male: HR = 1.827, 95% CI 1.449–2.303; Female: HR = 4.189, 95% CI 1.862–9.421). What’s more, among the anthropometric indices, BRI showed the optimal capability to predict T2DM (Male: AUC = 0.706, 95% CI 0.674–0.738; Female: AUC = 0.735, 95% CI 0.676–0.795).
Conclusion
An elevated BRI level in baseline was independently associated with incident T2DM. Baseline BRI improves the identification of patients at risk of T2DM and may enable early and optimized therapy to improve their outcomes.
Journal Article
Potential therapeutic targets for membranous nephropathy: proteome-wide Mendelian randomization and colocalization analysis
2024
The currently available medications for treating membranous nephropathy (MN) still have unsatisfactory efficacy in inhibiting disease recurrence, slowing down its progression, and even halting the development of end-stage renal disease. There is still a need to develop novel drugs targeting MN.
We utilized summary statistics of MN from the Kiryluk Lab and obtained plasma protein data from Zheng et al. We performed a Bidirectional Mendelian randomization analysis, HEIDI test, mediation analysis, Bayesian colocalization, phenotype scanning, drug bank analysis, and protein-protein interaction network.
The Mendelian randomization analysis uncovered 8 distinct proteins associated with MN after multiple false discovery rate corrections. Proteins related to an increased risk of MN in plasma include ABO [(Histo-Blood Group Abo System Transferase) (WR OR = 1.12, 95%CI:1.05-1.19, FDR=0.09, PPH4 = 0.79)], VWF [(Von Willebrand Factor) (WR OR = 1.41, 95%CI:1.16-1.72, FDR=0.02, PPH4 = 0.81)] and CD209 [(Cd209 Antigen) (WR OR = 1.19, 95%CI:1.07-1.31, FDR=0.09, PPH4 = 0.78)], and proteins that have a protective effect on MN: HRG [(Histidine-Rich Glycoprotein) (WR OR = 0.84, 95%CI:0.76-0.93, FDR=0.02, PPH4 = 0.80)], CD27 [(Cd27 Antigen) (WR OR = 0.78, 95%CI:0.68-0.90, FDR=0.02, PPH4 = 0.80)], LRPPRC [(Leucine-Rich Ppr Motif-Containing Protein, Mitochondrial) (WR OR = 0.79, 95%CI:0.69-0.91, FDR=0.09, PPH4 = 0.80)], TIMP4 [(Metalloproteinase Inhibitor 4) (WR OR = 0.67, 95%CI:0.53-0.84, FDR=0.09, PPH4 = 0.79)] and MAP2K4 [(Dual Specificity Mitogen-Activated Protein Kinase Kinase 4) (WR OR = 0.82, 95%CI:0.72-0.92, FDR=0.09, PPH4 = 0.80)]. ABO, HRG, and TIMP4 successfully passed the HEIDI test. None of these proteins exhibited a reverse causal relationship. Bayesian colocalization analysis provided evidence that all of them share variants with MN. We identified type 1 diabetes, trunk fat, and asthma as having intermediate effects in these pathways.
Our comprehensive analysis indicates a causal effect of ABO, CD27, VWF, HRG, CD209, LRPPRC, MAP2K4, and TIMP4 at the genetically determined circulating levels on the risk of MN. These proteins can potentially be a promising therapeutic target for the treatment of MN.
Journal Article
A case report of systemic lupus erythematosus combined with central serous chorioretinopathy treated with glucocorticoids
by
Ku, Ming
,
Rao, Qingqing
,
Wan, Qijun
in
Adult
,
Case Reports
,
Central Serous Chorioretinopathy - complications
2023
Glucocorticoids are generally contraindicated for use in central serous chorioretinopathy (CSC) because their use is considered to be an independent risk factor for CSC. There are rare reports regarding the treatment of systemic lupus erythematosus (SLE) combined with CSC. This current case report describes a rare case of a 24-year-old female patient with severely active SLE combined with CSC, whose vision was significantly restored after she was administered 120 mg methylprednisolone intravenously once a day for 3 days. This case report presents the clinical characteristics for the first time in terms of distinguishing between typical CSC and lupus chorioretinopathy. It also provides a review of the relevant literature. In patients with clinically severe active lupus nephritis combined with bilateral lupus chorioretinopathy, timely systemic application of appropriate doses of glucocorticoids is the preferred method to control the primary disease and serious ocular complications.
Journal Article
Association between triglyceride-to-high-density lipoprotein cholesterol ratio and prediabetes: a cross-sectional study in Chinese non-obese people with a normal range of low-density lipoprotein cholesterol
by
Wan, Qijun
,
Wu, Liling
,
Hu, Haofei
in
Biomedical and Life Sciences
,
Biomedicine
,
Body mass index
2022
Background
Evidence about the relationship between triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio and prediabetes (Pre-DM) in Chinese non-obese people with a normal range of low-density lipoprotein cholesterol (LDL-c) is limited. Therefore, the present study was undertaken to explore the link of the TG/HDL-C ratio on Pre-DM among non-obese Chinese population with a normal range of LDL-c.
Methods
This study was a cross-sectional study that enrolled 153163 non-obese individuals with a normal range of low-density lipoprotein cholesterol in a Chinese hospital from January 2010 to December 2014. Logistic regression model, generalized additive model (GAM), smooth curve fitting and a series of sensitivity analyses was used to evaluate the association between TG/HDL-C ratio and Pre-DM.
Result
The prevalence of Pre-DM was 9.77%.The median TG/HDL-C ratio was 0.671 (interquartile range, 0.468–1.010). After adjusting covariates, the results showed that TG/HDL-C ratio was positively associated with Pre-DM ((OR = 1.185, 95%CI 1.145–1.226). In addition, the TG/HDL-C ratio level has a non-linear relationship with the incidence of Pre-DM, in which the inflection point was 1.617. The effect sizes (OR) on the left and right sides of the inflection point were 1.312 (95%CI 1.242–1.386) and 0.980 (95%CI 0.898–1.070), respectively. And the sensitive analysis demonstrated the robustness of the results. Subgroup analysis showed a stronger association between TG/HDL-C ratio and Pre-DM in females and the population with 30 years < age < 40 years, 18.5 kg/m
2
< body mass index < 24 kg/m
2
, and ALT < 40U/L.
Conclusion
This study demonstrates a positive and non-linear relationship between TG/HDL-C ratio and Pre-DM in Chinese non-obese people with a normal range of low-density lipoprotein cholesterol. TG/HDL-C ratio is strongly related to Pre-DM when TG/HDL-C ratio is less than 1.617. It makes sense to reduce the TG/HDL-C ratio level below the inflection point from a treatment perspective.
Journal Article
Inverse relationship between LDL-C/HDL-C ratio and atrial fibrillation in chronic kidney disease patients
2024
Atrial fibrillation (AF) is more prevalent in individuals with chronic kidney disease (CKD) compared to the general population. While a potential inverse correlation between lipid levels and AF has been proposed, it remains unclear if this relationship applies to CKD patients. This study examined the connection between the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) and the likelihood of AF in CKD patients. Data was gathered from 21,091 consecutive CKD patients between 2006 and December 31, 2015. We examined the link between the LDL-C/HDL-C ratio and AF in CKD patients through binary logistic regression, as well as various sensitivity and subgroup analyses. The dataset that backs up these analyses is available at:
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230189
. Of the 21,091 CKD patients, 211 (1.00%) were diagnosed with AF. The cohort, predominantly male (79.93%), had a mean age of 60.89 ± 10.05 years. The mean LDL-C/HDL-C ratio was 1.39 ± 0.35. After adjusting for covariates, a significant inverse association was observed between the LDL-C/HDL-C ratio and the incidence of AF in CKD patients (OR = 0.422, 95% CI 0.273–0.652, P = 0.00010). The robustness of these findings was confirmed through sensitivity analysis. Subgroup analysis revealed a strong correlation between the LDL-C/HDL-C ratio and incident AF in patients without hypertension (HR = 0.26, 95% CI 0.15–0.45). Conversely, this association was absent in hypertensive patients (HR = 1.09, 95% CI 0.54–2.17). Our research shows an independent inverse correlation between the LDL-C/HDL-C ratio and the risk of AF in CKD patients. It is advised to refrain from excessively aggressive reduction of LDL levels in CKD patients, as this could elevate the risk of developing AF.
Journal Article
The role of B lymphocyte subsets in nephrotic syndrome: functions, mechanisms, clinical significance and future perspectives
2025
B lymphocytes play a critical role in the pathogenesis of nephrotic syndrome (NS). This comprehensive review explores the phenotypic characteristics, pathogenic mechanisms, and clinical translational value of B cell subsets in different types of nephrotic syndrome. Studies demonstrate that B cells participate in disease development through multiple mechanisms, including autoantibody production, T cell function regulation, and cytokine secretion. In minimal change disease, B cell-mediated immune dysregulation is primarily characterized by decreased CD19+ cells and increased plasmablasts. Membranous nephropathy patients exhibit increased naïve B cells and decreased memory B cells, while focal segmental glomerulosclerosis is characterized by elevated class-switched memory B cells. These B cell subset alterations can serve as biomarkers for disease activity assessment and prognosis prediction. B cell-targeted therapies, such as anti-CD20 monoclonal antibodies, have demonstrated significant therapeutic efficacy in nephrotic syndrome, further confirming the pivotal role of B cells in its pathogenesis. Different pathological types of NS show significant differences in B cell subset changes, pathogenic mechanisms, and therapeutic responses. Primary and secondary nephrotic syndrome exhibit important distinctions in B cell activation mechanisms, subset imbalance patterns, degree of renal tissue infiltration, and autoantibody profiles. Age factors significantly influence B cell development, function, and therapeutic response, with notable differences between pediatric and adult patients in B cell subset distribution, treatment efficacy, and pharmacokinetics. With the application of emerging technologies such as single-cell sequencing, in-depth analysis of B cell subset characteristics and their interactions with other immune cells will provide new insights for developing more precise diagnostic and therapeutic strategies. However, current methodological heterogeneity challenges in research, including patient population differences, inconsistent B cell subset definitions, technical platform variations, and non-uniform clinical assessment criteria, limit the comparability of research results and clinical applications. Future efforts need to establish standardized B cell monitoring protocols and precision diagnostic systems, develop next-generation B cell-targeted therapeutic strategies, and deeply explore age-specific mechanisms and systems biology research to achieve precision medicine in nephrotic syndrome.
Journal Article
Immunoglobulin heavy chain gene rearrangement in heavy chain deposition disease suggests it is a plasma cell disease: a case report
by
Xu, Ricong
,
Rao, Qingqing
,
Wan, Qijun
in
Antineoplastic Agents - therapeutic use
,
Bone marrow
,
Bortezomib - therapeutic use
2022
Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes. Truncated heavy chains are thought to be associated with plasma cell disease (PCD), but previous bone marrow cytology tests showed that only 30% of HCDD cases are related to PCDs. We report the first known use of immunoglobulin heavy chain (IGH) gene rearrangement to diagnose a patient with γ3-HCDD, although bone marrow morphology test identified no abnormalities. Our findings provide strong evidence for a correlation between PCDs and HCDD, which could help understand the genetic background underlying abnormal heavy chains and assess disease prognosis. Further, concordant with previous findings, bortezomib-based chemotherapy had a good therapeutic effect in our patient. We summarize the experience of diagnosing and treating a case of HCDD, and combine this with a literature review to further explore the correlation between PCDs and HCDD, which has important clinical value.
Journal Article
Mean arterial pressure at the initiation of continuous renal replacement therapy as a prognostic indicator in patients with acute kidney injury
by
Song, Haiying
,
Wan, Qijun
,
Hu, Haofei
in
28- and 90-day mortality
,
acute kidney injury
,
Acute Kidney Injury - etiology
2025
Acute kidney injury (AKI) is a common complication in critically ill patients, with approximately 5% requiring continuous renal replacement therapy (CRRT). This study investigated the relationship between mean arterial pressure (MAP) and 28- and 90-day mortality in critically ill AKI patients treated with CRRT.
This secondary analysis of a bicenter, retrospective, observational study included patients with AKI who were treated with CRRT from January 2009 to September 2016. Mortality at 28 and 90 days post-CRRT initiation was analyzed using multivariate regression, generalized additive models, smooth curve fitting, and sensitivity analyses.
A total of 1,142 patients were included, with 28-day and 90-day mortality rates of 62.1% and 71.8%, respectively. In multivariable-adjusted Cox models, MAP was inversely correlated with the risk of 28-day and 90-day mortality after adjusting for covariates. Hazard ratios (HRs) were calculated per 1 mmHg increment of MAP: adjusted HR for 28-day mortality 0.985 (
< 0.00001) and for 90-day mortality 0.987 (
= 0.00002). The adjusted HRs for 28-day and 90-day mortality in patients in the highest tertile of MAP compared with those in the lowest tertile were 0.682 (95% CI 0.543-0.857) and 0.730 (95% CI 0.592-0.899), respectively. Patients were grouped using MAP thresholds of <65 mmHg, 65-71.85 mmHg, and ≥71.85 mmHg, with similar results observed. Sensitivity analyses confirmed the inverse relationship between higher MAP before CRRT and lower mortality.
The higher the MAP before CRRT is, the lower the 28- and 90-day mortality of critically ill patients with AKI who are treated with CRRT.
Journal Article
Nonlinear association between proteinuria levels and the risk of cardiovascular disease events and all-cause mortality among chronic kidney disease patients
by
Song, Haiying
,
Wan, Qijun
,
Hu, Haofei
in
all-cause death
,
Cardiovascular disease
,
Cardiovascular diseases
2024
The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial.
In this investigation, we conducted a retrospective analysis involving 1138 patients who were registered in the CKD-Research of Outcomes in Treatment and Epidemiology (ROUTE) study. The primary outcome of this study was the composite of cardiovascular events or all-cause death. Cox proportional hazards regression, smooth curve fitting, piecewise linear regression, and subgroup analyses were used.
The mean age of the included individuals was 67.3 ± 13.6 years old. Adjusted hazard ratios (HRs) for UPCR in middle and high groups, compared to the low group, were 1.93 (95% CI: 1.28-2.91) and 4.12 (95% CI: 2.87-5.92), respectively, after multivariable adjustment. Further adjustments maintained significant associations; HRs for middle and high groups were 1.71 (95% CI: 1.12-2.61) and 3.07 (95% CI: 2.08-4.54). A nonlinear UPCR-primary outcome relationship was observed, with an inflection point at 3.93 g/gCr.
Among non-dialyzed patients with stage G2-G5 CKD, a nonlinear association between UPCR and the primary outcome was observed. A higher UPCR (when UPCR < 3.93 g/gCr) was an independent predictor of the primary outcome. Importantly, our study predates SGLT2 inhibitor use, showcasing outcomes achievable without these medications. Future research considerations will involve factors like SGLT-2 inhibitor utilization.
Journal Article
Neural epidermal growth factor-like 1 expression predicts end-stage renal disease in phospholipase A2 receptor–negative membranous nephropathy: A retrospective cohort stratified by systemic lupus erythematosus
by
Cheng, Yuan
,
Yue, Shuling
,
Song, Haiying
in
Adult
,
Biomarkers - analysis
,
Biomarkers - metabolism
2025
Background
Neural epidermal growth factor-like 1 protein has emerged as a significant antigen in membranous nephropathy, an important cause of nephrotic syndrome in adults. However, the prognosis of neural epidermal growth factor-like 1–associated membranous nephropathy remains limited and requires further exploration.
Methods
A Chinese retrospective cohort of 446 patients diagnosed with membranous nephropathy on renal biopsy was categorized into phospholipase A2 receptor-associated (n = 358) and phospholipase A2 receptor–negative (n = 88) membranous nephropathy groups. The phospholipase A2 receptor–negative group was subjected to neural epidermal growth factor-like 1 fluorescence staining. Multivariate regression analyses, stratified analyses, and Kaplan–Meier analyses were used to explore the correlation of neural epidermal growth factor-like 1 with the risk of end-stage renal disease.
Results
We identified 11 cases of neural epidermal growth factor-like 1-associated membranous nephropathy, accounting for 12.7% of phospholipase A2 receptor–negative membranous nephropathy cases. These patients were predominantly young women with a history of fairness cream use. In patients with phospholipase A2 receptor–negative membranous nephropathy, multivariable regression analysis showed that the neural epidermal growth factor-like 1-positive group had a higher risk of end-stage renal disease compared with the neural epidermal growth factor-like 1-negative group (hazard ratio = 3.2, p = 0.026). Stratified analysis showed that this association was particularly significant in patients with systemic lupus erythematosus (hazard ratio = 5.1, p = 0.041). Kaplan–Meier analysis also revealed a higher risk in neural epidermal growth factor-like 1–positive patients (p = 0.003).
Conclusion
Neural epidermal growth factor-like 1 expression is an independent risk factor for end-stage renal disease, especially in patients with systemic lupus erythematosus, with an incidence rate of approximately 12.7% in patients with phospholipase A2 receptor–negative membranous nephropathy.
Journal Article