ObjectiveCrohn's disease (CD) is closely associated with disorders of uric acid metabolism. Our previous research found an association between phthalate exposure and oxidative stress in CD, suggesting a potential role for phthalates in metabolic disorders. Therefore, this study aims to examine their influence on uric acid metabolism in patients with CD.MethodsWe designed a cross-sectional study involving 117 patients with CD. Ten urinary phthalates metabolites (mPAEs) were detected by gas chromatography-tandem mass spectrometry, and the serum uric acid (SUA) levels were tested. Correlation analysis and Bayesian kernel machine regression (BKMR) models were applied separately to evaluate the associations.ResultsThe prevalence of hyperuricemia was 12.8% (15/117) in CD patients. None of them were obese or had abnormal renal function. In males, we identified significant positive associations between SUA and eight mPAEs (MMP, MIBP, MBP, MBzP, MOP, MEOHP, MEHHP, & MECPP). However, no positive associations between mPAEs and SUA were found in females. After BKMR analysis and multivariate adjustments, we found that the average SUA (μmol/L) increased by 1.36-fold, and the odds ratio for hyperuricemia increased by 1.25-fold, when overall phthalates exposure increased from 25% to 75% in male CD patients. This suggests a potential link between phthalates exposure and uric acid metabolism in male patients with CD. Furthermore, oxidative stress mediated approximately 5% of the association, indicating it is a partial, but not primary, mechanism in this process.ConclusionsPhthalates exposure positively correlated with SUA in male CD patients. Effective PAE exposure control in patients with CD may reduce the risk of hyperuricemia.

Background and AimsImmunoglobulin A nephropathy (IgAN) is a clinical and pathological syndrome with heterogenous manifestation and progression. The prognostic nutritional index (PNI) and the controlling nutritional status (CONUT) score, indicators of nutritional status and systemic inflammation, are associated with poor prognosis in dialysis patients. This study was aimed to investigate the predictive value of the objective nutritional indices (PNI and CONUT) for renal progression in IgAN patients.MethodsA multicenter retrospective study was conducted in biopsy-proven IgAN patients. Baseline characteristics were obtained within 1 week before renal biopsy. The renal composite endpoint comprised an estimated glomerular filtration rate (eGFR) decline >50%, a doubling of baseline serum creatinine, or the occurrence of end stage kidney disease (ESKD). The receiver operating characteristic curve analysis was conducted to determine the optimal cut-off value of PNI and CONUT. The Kaplan–Meier curve estimated the cumulative renal-survival rate. Univariate and multivariate Cox regression models were preformed to investigate the association between objective nutritional indices and renal outcomes.ResultsA total of 659 IgAN patients participated in this study. During a median follow-up period of 45 months, 68 patients (10.32%) achieved the composite endpoint. The Kaplan–Meier curve revealed that renal-survival rate was significantly higher in high PNI group (PNI > 46.5; p < 0.001) and low CONUT group (CONUT ≤2; p < 0.001). Even after adjustment of traditional risk factors, including sex, age, mean arterial pressure, hemoglobin, uric acid, eGFR, triglycerides, 24-h urinary protein, E score, T score, and treatment with ACEI/ARB, low PNI [hazard ratio (HR) = 2.514, 95% confidence intervals (CI) = 1.212–5.215, p = 0.013] and high CONUT (HR = 2.152, 95% CI = 1.087–4.259, p = 0.028) remained as independent risk factors for poor renal outcomes.ConclusionThis study suggested that low PNI and high CONUT were significantly and independently correlated with poor prognosis in patients with IgAN at CKD stages 1–4. The PNI and CONUT are inexpensive and straightforward indicators to help clinicians improve IgAN management.

ObjectiveThe study aimed to evaluate the performance of ultrasonographic medial gastrocnemius muscle thickness (MGMT) and pennation angle (MGMPA) in diagnosing sarcopenia among patients on maintenance hemodialysis (MHD).MethodsThe MGMT and MGMPA were measured ultrasonographically. Baseline characteristics were compared between the sarcopenia and non-sarcopenia groups. Correlations between ultrasound parameters and sarcopenia indicators were evaluated. The diagnostic performance of the ultrasound parameters was assessed using receiver operating characteristic (ROC) curve analysis. Multivariable logistic regression analysis was conducted to identify independent predictors associated with sarcopenia, followed by the construction and validation of a diagnostic nomogram. Additionally, bootstrap mediation analysis assessed the direct and indirect effects of sonographic parameters on sarcopenia.ResultsThis study cohort comprised 221 MHD patients. Both MGMT (12.8 vs. 16.5 mm, p < 0.001) and MGMPA (26.35° vs. 29.73°, p < 0.001) were significantly reduced in the sarcopenia group compared to the non-sarcopenia group. MGMT exhibited significant positive correlations with calf circumference, appendicular skeletal muscle mass index (ASMI), appendicular skeletal muscle mass (ASM), body mass index (BMI), and handgrip strength, alongside a significant inverse correlation with the SARC-CalF score. MGMT demonstrated good diagnostic performance for sarcopenia, yielding an area under the curve (AUC) of 0.823 (p < 0.001). Multivariable logistic regression identified MGMT, BMI, older age, and male gender as independent predictors of sarcopenia. A predictive nomogram incorporating these factors demonstrated excellent discrimination (AUC = 0.873), good calibration, and potential clinical decision-making value across a wide threshold probability range. Mediation analysis confirmed a significant direct association between MGMT and the presence of sarcopenia in both the age model (ADE = −0.00303, p < 0.001) and the serum albumin model (ADE = −0.00251, p < 0.001), with no significant mediating effects observed for either variable.ConclusionUltrasonographic measurement of MGMT demonstrates high diagnostic performance and serves as a reliable, independent predictor for sarcopenia in patients undergoing maintenance hemodialysis, highlighting its potential as a practical, non-invasive screening tool in clinical practice.

Trihalomethanes (THMs) are suspected neurotoxicants, yet their relationships with depression remain unclear. This study examined the associations between blood THM concentrations and depressive symptoms, assessed by the Patient Health Questionnaire-9 (PHQ-9), in 2,130 postmenopausal U.S. women. Blood concentrations of bromodichloromethane (BDCM), dibromochloromethane (DBCM), and brominated trihalomethanes (Br-THMs) showed positive dose-response associations with depressive symptoms (PHQ-9 >= 5; all P for trend <0.05). Compared with the lowest exposure category, participants in the highest category of BDCM (T3), DBCM (>= 75th percentile), and Br-THMs (Q4) had increased odds ratios (ORs) for depressive symptoms of 1.38 (95% confidence interval: 1.04-1.82), 1.62 (1.25-2.09), and 1.46 (1.02-2.09), respectively. Further mechanistic experiments in a human neuroimmune organ-on-a-chip model (SH-SY5Y cells cocultured with THP-1 cells) showed that environmentally relevant exposure (0.001 mM BDCM and 0.0005 mM DBCM) increased interleukin-1 beta (IL-1 beta) levels and reduced 5-hydroxytryptamine (5-HT) levels. Low-dose BDCM exposure (0.001 mM) also induced neuronal cytoskeletal changes in SH-SY5Y cells, as reflected by changes in mean fluorescence intensity and skeletonized area. Together, our findings suggest that exposure to Br-THMs may be associated with depressive symptoms in postmenopausal women, potentially via IL-1 beta-mediated neuroinflammation and neurotransmitter imbalance.

BackgroundEvidence that depressive symptoms precede physical multimorbidity has relied mainly on symptoms measured at one timepoint. We aimed to determine whether depressive symptom burden accumulated across repeated assessments was associated with the subsequent development of physical multimorbidity.MethodsIn this multicohort study, we used data from the Health and Retirement Study (HRS), English Longitudinal Study of Ageing (ELSA), Survey of Health, Ageing and Retirement in Europe (SHARE), and China Health and Retirement Longitudinal Study (CHARLS). Scores from three assessments in HRS, ELSA, and SHARE and two in CHARLS were converted to percentage of maximum possible and integrated over time. The final assessment defined the landmark. Participants with fewer than two of seven physical conditions were followed for incident multimorbidity. Cohort-specific complementary log-log models were combined by random-effects meta-analysis.Findings40,418 participants were included and 14,332 developed physical multimorbidity. The adjusted HR per 1-SD higher cumulative burden was 1.086 (95% CI 1.054-1.119) in HRS, 1.166 (1.112-1.222) in ELSA, 1.087 (1.054-1.121) in SHARE, and 1.179 (1.124-1.236) in CHARLS. The pooled HR was 1.125 (1.078-1.174; I²=80.9%; 95% prediction interval 1.031-1.228). Adjusted risk differences between the 90th and 10th percentiles ranged from 5.8 to 11.7 percentage points over cohort-specific horizons of 4-7 years. When repeated burden and the initial symptom score were mutually adjusted, their pooled HRs were 1.102 (1.055-1.152) and 1.022 (0.997-1.047), respectively. Associations varied least for stroke (pooled HR 1.131, 1.095-1.169; I²=0.1%) and hypertension (1.052, 1.027-1.078; I²=19.4%).InterpretationGreater depressive symptom burden across repeated assessments was associated with a higher subsequent rate of physical multimorbidity, although the magnitude varied between cohorts. The association persisted after accounting for the initial symptom score, but the study did not assess clinical prediction and cannot establish whether reducing symptom burden would slow disease accumulation.

There is an urgent need to implement population-based actions to prevent diabetes mellitus (DM) in China. However, the current knowledge is limited on a prospective association of seafood intake with DM risk in Chinese adults. We aimed to determine the association between seafood consumption and the incident DM in a nationwide cohort of Chinese populations. A prospective cohort study of 104,816 participants, free of DM, aged ≥ 40 years across various geographical regions in China was conducted at baseline (China Cardiometabolic Disease and Cancer study). Habitual consumptions of seafood were assessed using a semi-quantitative food frequency questionnaire, and DM was diagnosed according to the WHO 1999 criteria. Primary outcomes were the incident DM, presented as hazard rations (HRs) with 95

Objective: This study aimed to evaluate the prognostic value of estimated pulse wave velocity (ePWV) for predicting all-cause and cardiovascular mortality in patients with cardiovascular-kidney-metabolic (CKM) syndrome. Methods: We analyzed data from 9735 adults with CKM syndrome in the National Health and Nutrition Examination Survey (NHANES, 1999-2018). ePWV was calculated using a validated formula based on age and blood pressure. Participants were categorized into ePWV quartiles (Q1: <= 6.44 m/s; Q2: 6.44-7.41 m/s; Q3: 7.41-8.96 m/s; and Q4: > 8.96 m/s). Mortality outcomes were assessed via linkage to the National Death Index. Cox proportional hazards models were employed to estimate hazard ratios, adjusting for demographic, clinical, and laboratory covariates. Results: During a median follow-up of 20 years, higher ePWV quartiles showed progressively increased mortality risks. In fully adjusted models, Q4 exhibited substantially elevated hazards for all-cause mortality (HR: 10.46, 95% CI: 5.38-20.33) and cardiovascular mortality (HR: 14.02, 95% CI: 3.67-53.51) versus Q1. In the overall cohort, PWV showed a significant positive linear relationship with both cardiovascular and all-cause mortality (overall p < 0.05; nonlinear p > 0.05). Subgroup analyses revealed stronger associations in nonadvanced CKM stages (Stages 0-2) and older adults (p < 0.05). Conclusion: ePWV is a robust, noninvasive predictor of mortality in CKM syndrome, with potential utility for risk stratification and therapeutic targeting. These findings support incorporating arterial stiffness assessment into CKM management protocols.

Anemia is associated with cognitive decline, but the influence of its temporal patterns on cognitive trajectories remains unknown. This study investigated the longitudinal association between dynamic anemia patterns (persistent, intermittent, never) and cognitive function in middle-aged and older Chinese adults. We analyzed data from 6,364 participants aged ≥ 45 years in the China Health and Retirement Longitudinal Study (2011–2020). Based on 2011 and 2015 hemoglobin measurements, participants were categorized as never, intermittent, or persistent anemia. Linear mixed-effects models assessed associations with cognitive function. Sensitivity analyses included multiple imputation, varying anemia thresholds, and inverse probability weighting. Based on hemoglobin levels in 2011 and 2015, 4,769 (74.9

Phthalates have been linked to higher mortality, but evidence on their relationship with epigenetic aging remains limited, particularly among older adults. We investigated associations between urinary phthalate metabolites and DNA methylation (DNAm)-derived epigenetic age acceleration (EAA) and examined EAA as a potential mediator for the phthalate-mortality association. We analyzed 611 U.S. adults aged ≥ 50 years without baseline cardiovascular diseases (CVD) or cancer diagnosis from the 1999–2002 U.S. National Health and Nutrition Examination Survey (NHANES), followed for mortality through 2019. Baseline urinary concentrations of four phthalate metabolites and EAA derived from four DNAm clocks were analyzed using survey-weighted linear regression, Bayesian Kernel Machine Regression, and quantile-based g-computation for individual and mixture effects. Higher monobenzyl phthalate (MBzP) was associated with accelerated HannumAge (0.60 years per log-unit increase) and was positively associated with all-cause, cancer, and CVD mortality. Mixture analyses suggest MBzP as the primary contributor to accelerated HannumAge, PhenoAge, and GrimAge, despite no significant overall mixture effects. Mediation analyses indicated that EAA partially explained these associations, with the largest proportion mediated for cancer mortality (3.9%-9.2% across clocks). These findings suggest that among older U.S. adults, urinary MBzP was associated with accelerated epigenetic aging, which partially mediated the MBzP-mortality association, highlighting the need to reduce phthalate exposure and supporting DNAm clocks as sensitive biomarkers of environmental toxicity.

Early-life exposure to di(2-ethylhexyl) phthalate (DEHP) has been associated with compromised immune outcomes in childhood, while evidence regarding DEHP substitutes, such as di-isononyl phthalate (DiNP), di-isononyl cyclohexane-1,2-dicarboxylate (DiNCH) and di(2-ethylhexyl) terephthalate (DEHTP), remains limited. This study analyzed urinary concentrations of 18 phthalate metabolites, including legacy phthalates and the newer substitutes, and examined their associations with overall infection risk among 1989 U.S. children representative of the US population stratified into three vulnerable age groups (3-5, 6-11, and 12-19 years). We applied logistic and mixture models to examine the associations. We found a higher infection risk associated with DiNP metabolite concentrations (MONP: mono-oxo-isononyl phthalate and MCOP: mono-carboxy-isooctyl phthalate) in children aged 3-5 years (3rd vs 1st tertile, MONP OR: 1.94, 95% CI: 1.12, 3.34) and adolescents aged 12-19 years (MONP OR: 5.49, 95% CI: 2.30, 13.06; MCOP OR: 4.91, 95% CI: 2.11, 11.40). Adolescent urinary concentrations of other phthalate metabolites were associated with higher infection odds, including mono-benzyl phthalate (3rd vs 1st tertile OR: 3.39, 95% CI: 1.56, 7.37), mono-(3-carboxypropyl) phthalate (OR: 2.97, 95% CI: 1.47, 5.99), mono-isobutyl phthalate (OR: 1.71, 95% CI: 1.01, 2.87), mono-hydroxy-isobutyl phthalate (OR: 1.95, 95% CI: 1.09, 3.48), and mono-2-ethyl-5-carboxypentyl phthalate (OR: 2.24, 95% CI: 0.97, 5.16). Among adolescents, each tertile increase in mixture concentration was associated with a higher infection risk (OR: 2.45, 95% CI: 1.26, 4.77). Regarding non-phthalate alternatives, only an isolated deleterious association was found for DiNCH in boys but not girls aged 6-11 years. Although these associations should be validated in longitudinal cohorts, our results suggest that children's exposure to specific phthalates and phthalate mixtures may increase susceptibility to infections, and that DiNP does not appear to be a safe substitute for DEHP regarding immune-related outcomes. More observational and toxicological studies are needed, particularly for newer non-phthalate substitutes such as DiNCH and DEHTP.

BackgroundLimited data exists on relationship between body mass index (BMI) trajectory and stroke risk among elderly Chinese individuals. This study aimed to examine the association of BMI trajectory with stroke among people aged 65 years and older in China.Methods150, 813 participants with at least three BMI measurements from 2012 to 2022 were included. Group-based trajectory modeling was used to identify BMI trajectories. Cox proportional hazards regression models were used to examine the association between BMI trajectories and incidence of stroke.ResultsWe identified 3 (stable, slowly increased, greatly increased), 4 (slightly decreased, stable, slowly increased, sharply increased), 4 (large decreased, slightly decreased, stable, moderate increased) and 4 (substantially decreased, slightly decreased, stable, slightly increased) BMI trajectories in groups with underweight, normal weight, overweight and obesity at baseline, respectively. Taking the stable weight subgroup as the reference group, among subjects with normal weight, the adjusted hazard ratios (HRs) [95% confidence interval (CI)] were 0.93 (0.88, 0.99) for slightly decreased group, 1.07 (1.03, 1.13) for slowly increased group, and 1.12 (1.02, 1.23) for sharply increased group. Among participants with overweight, the HRs (95% CI) were 0.84 (0.75, 0.95) for large decreased group and 0.94 (0.89, 0.99) for slightly decreased group. Among participants with obesity, the HRs (95% CI) were 0.79 (0.64, 0.96) for large decreased group.ConclusionAmong people aged 65 years and older, increased BMI was associated with a higher risk of stroke, while decreased BMI was related to reduced risk of stroke.

AIMS:Monoclonal gammopathy-associated kidney lesions typically present with a single pathological pattern, but the coexistence of multiple patterns in the same patient is rare and poorly characterized. This study aimed to delineate the clinicopathological spectrum and outcomes of these complex cases. METHODS AND RESULTS:Twenty-three patients with coexistent pathological patterns were identified from native kidney biopsies. The most frequent combinations were light chain cast nephropathy (LCCN) with light chain deposition disease (LCDD) (34.8%), followed by LCCN with light chain amyloidosis (AL) (21.7%) and LCCN with light chain proximal tubulopathy (LCPT) (21.7%). Multiple myeloma was the predominant underlying haematological disorder (87.0%). Compared with isolated AL, the LCCN+AL group showed more severe acute tubular injury and chronic tubulointerstitial damage (both P < 0.05). The LCCN+LCDD group exhibited more severe acute injury but milder chronic fibrosis than isolated LCDD (P < 0.05). The LCCN+LCPT group had the most favourable prognosis, whereas the LCCN+AL group had the worst, with a median survival of only 32 months and significantly higher mortality than isolated LCCN, isolated AL and LCCN+LCPT groups (all P < 0.05). CONCLUSIONS:Monoclonal gammopathy-associated kidney lesions with coexistent pathological patterns represent a highly heterogeneous entity with distinct features and varied prognoses. The combination of LCCN with AL identifies a particularly high-risk group. Kidney biopsy is crucial for precise classification and prognosis assessment.

OBJECTIVE:In some patients with membranous nephropathy (MN) receiving rituximab therapy, treatment failure may be partly related to the development of anti-rituximab antibodies (ADAs). This study aimed to establish a highly sensitive time-resolved fluoroimmunoassay (TRFIA) for detecting ADAs in these patients. METHOD:A streptavidin-coated microplate was used as the solid phase, with biotinylated rituximab as the capture antibody and Eu3+ -labeled rituximab as the detection antibody. A bridging assay was developed to detect ADAs, and the method was optimized, validated, and preliminarily applied in clinical testing. RESULTS:The developed TRFIA exhibited a linear detection range of 12.5 ng/mL to 800 ng/mL, with a detection limit (LOD) of 3.93 ng/mL. The intra‑assay coefficient of variation (CV) ranged from 3.07% to 7.90%, and the inter‑assay CV ranged from 2.57% to 11.32%. Recovery rates spanned 87.06% to 104.11%, and no cross‑reactivity was detected with anti‑obinutuzumab or anti‑eculizumab. Compared to enzyme‑linked immunosorbent assay (ELISA), the TRFIA showed superior sensitivity (3.9 ng/mL vs. 10 ng/mL) and maintained strong agreement in sample detection (p < 0.0001). CONCLUSION:This assay demonstrates specific potential clinical utility in monitoring resistance to rituximab, providing valuable guidance for optimizing anti-CD20 monoclonal antibody therapy and developing personalized treatment plans.

Purpose:To evaluate the efficacy and safety of telitacicept for the treatment of immunoglobulin A nephropathy (IgAN). Methods:This study enrolled patients with biopsy-confirmed IgAN who had 24-hour proteinuria exceeded 0.75 g/day and received telitacicept treatment for at least 3 months. Using propensity score matching, patients were matched in a 1:1:1 ratio with those who received only supportive or immunosuppressive (IS) therapy (glucocorticoid with or without mycophenolate mofetil). The primary outcomes were percentage changes in 24-hour proteinuria and estimated glomerular filtration rate (eGFR) during the 12-month follow-up period. Results:Each group included 24 patients. At 12 months, telitacicept reduced 24-hour proteinuria by 1.50 g/day (57.61%) from baseline, while the supportive treatment group had a reduction of 0.60 g/day (17.11%) and the IS treatment group had a reduction of 1.60 g/day (59.49%). The percentage change in 24-hour proteinuria in the telitacicept group was similar to that in the IS treatment group, and both groups were superior to the supportive treatment group. The telitacicept group exhibited a minor decline in eGFR of 2.1 mL/min/1.73 m2 (-4.23%), while the supportive treatment group and IS therapy group showed declines of 6.05 mL/min/1.73 m2 (-13.87%) and 2.65 mL/min/1.73 m2 (-5.65%), respectively. The incidence of adverse events was lower in the telitacicept group than that in the IS treatment group. Meanwhile, there was no statistical difference in the remission rates (including complete remission and partial remission) between the telitacicept and IS treatment groups, and both groups were superior to the supportive treatment group. Conclusion:Telitacicept can reduce 24-hour proteinuria in patients with IgAN and stabilize eGFR with good safety during follow-up. These findings suggest that telitacicept may represent a safer and effective therapeutic alternative to conventional IS regimens for reducing proteinuria and preserving renal function in patients with IgAN, particularly those at high risk of disease progression.

Metabolic-associated fatty liver disease (MAFLD) remains a major global public health concern, yet comprehensive identification tools integrating metabolic biomarkers with dietary and lifestyle factors remain limited. This study included 11,934 participants (22.07% with MAFLD). After multicollinearity diagnosis using VIF, we applied LASSO regression combined with stepwise logistic regression (LR) to screen key variables. Based on the identified variables, eight machine learning models were developed and compared. LR demonstrated optimal performance in the held‑out internal test set, achieving an AUC of 0.904 (95% CI: 0.894–0.915) with well‑balanced sensitivity (0.891) and specificity (0.781), and showed preferred generalizability with the smallest training‑test performance gap. Sensitivity analyses were performed to evaluate the variable selection strategy and address concerns about the homology between FLI/HSI and MAFLD. Four LR models were compared: a full‑variable model (excluding FLI and HSI), the screened‑variable model, a FLI + HSI‑only model, and a metabolic‑excluded model. The screened‑variable model achieved comparable performance to the full‑variable model while using fewer variables, and substantially outperformed the FLI + HSI‑only model in detecting MAFLD cases. The metabolic‑excluded model yielded a substantially lower AUC (0.792), confirming that metabolic variables are key drivers of performance. SHAP analysis identified BMI, TyG index, LAP, and HDL (negative contribution) as the most influential predictors. This reduced‑variable, interpretable LR model may support MAFLD risk stratification and individualized prevention, though external validation is warranted before clinical implementation.

Trihalomethanes (THMs) are suspected neurotoxicants, yet their relationships with depression remain unclear. This study examined the associations between blood THM concentrations and depressive symptoms, assessed by the Patient Health Questionnaire-9 (PHQ-9), in 2,130 postmenopausal U.S. women. Blood concentrations of bromodichloromethane (BDCM), dibromochloromethane (DBCM), and brominated trihalomethanes (Br-THMs) showed positive dose-response associations with depressive symptoms (PHQ-9 ≥ 5; all P for trend <0.05). Compared with the lowest exposure category, participants in the highest category of BDCM (T3), DBCM (≥75th percentile), and Br-THMs (Q4) had increased odds ratios (ORs) for depressive symptoms of 1.38 (95% confidence interval: 1.04-1.82), 1.62 (1.25-2.09), and 1.46 (1.02-2.09), respectively. Further mechanistic experiments in a human neuroimmune organ-on-a-chip model (SH-SY5Y cells cocultured with THP-1 cells) showed that environmentally relevant exposure (0.001 mM BDCM and 0.0005 mM DBCM) increased interleukin-1 beta (IL-1β) levels and reduced 5-hydroxytryptamine (5-HT) levels. Low-dose BDCM exposure (0.001 mM) also induced neuronal cytoskeletal changes in SH-SY5Y cells, as reflected by changes in mean fluorescence intensity and skeletonized area. Together, our findings suggest that exposure to Br-THMs may be associated with depressive symptoms in postmenopausal women, potentially via IL-1β-mediated neuroinflammation and neurotransmitter imbalance.

BACKGROUND:Primary membranous nephropathy is a widely recognized autoimmune disease associated with podocyte antigens; the most important autoantigen is PLA2R1. PLA2R1 and HLA-DQA1 play important roles in the production of pathogenic antibodies. The purpose of this study was to observe the relationship between gene polymorphisms and primary membranous nephropathy and explore the clinical functional clues of PLA2R1 and HLA-DQA1 genes affecting treatment responsiveness. METHOD:The study enrolled 89 patients with primary membranous nephropathy and 91 healthy people as a control. Single-nucleotide polymorphism loci (seven on PLA2R1 and two on HLA-DQA1) were identified using the PCR-Sanger technique. The patients were followed up until the 12th month, and relevant clinical data were collected. The relationship between these single-nucleotide polymorphism loci and primary membranous nephropathy remission was analyzed. RESULT:Genotypic and allelic frequency distributions for six single-nucleotide polymorphisms within PLA2R1 (rs4664308, rs3792189, rs3792192, rs1870102, rs17831251, and rs35771982) and one in HLA-DQA1 (rs2187668) were associated with morbidity of primary membranous nephropathy. Single-nucleotide polymorphisms rs1870102, rs17831251, and rs2187668 were statistically significant in the genetic model analysis. The odds ratio for primary membranous nephropathy in patients carrying rs2187668 GG and rs1870102 AA was 52.875. We found that PLA2R1 single-nucleotide polymorphism rs36771982 was related to proteinuria remission at the 12th month, and found in further analysis that PLA2R1 single-nucleotide polymorphisms rs3792189, rs3792192, rs17831251, and rs35771982 were related to treatment response in the RTX group. CONCLUSION:In this study, we found several PLA2R1 and HLA-DQA1 single-nucleotide polymorphism loci associated with primary membranous nephropathy morbidity and that some PLA2R1 single-nucleotide polymorphism loci were related to the treatment response of patients with primary membranous nephropathy.