Introductions: Patients with primary podocytopathies such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome are at risk for adverse outcomes. This study reports on the long -term outcomes, specifically kidney failure and death among patients treated for primary podocytopathies in a tertiary centre in Singapore. Materials and Methods: This was a single -centre, retrospective cohort study of all adults aged ≥21 years old diagnosed between 2016 and 2020 with MCD and FSGS with nephrotic -range proteinuria. We excluded patients with membranous nephropathy and secondary glomerulonephritides (lupus nephritis, ANCA - associated vasculitis, membranoproliferative glomerulonephritis, and diabetic nephropathy). Sociodemographic, comorbidity, laboratory and pharmacotherapy data were retrieved from the electronic medical records. The outcomes assessed were incidence of death or kidney failure (estimated glomerular filtration function [eGFR]<15 ml/min/1.73 m2 or required kidney replacement therapy). Results: Sixty patients (Chinese 80%, Malay 6%, Indian 3% and other races 3%) with MCD (37 patients) and FSGS (23 patients) were included. The morphological lesions in FSGS included cellular (n=2), tip (n=2), perihilar (n=7), collapsing (n=3) and not otherwise specified (n=17). At a median follow -up of 26.3 (8.9, 50.3) months, 12 (20%) outcomes were recorded, 11 (47.8%; death 6 and kidney failure 5) in the FSGS group and 1 (2.7%; died) in the MCD group. The causes of death were attributed to kidney failure (n=1), cardiovascular disease (n=1), infection (n=3); and unknown (n=2). The Kaplan -Meier survival curve showed that patients with MCD had better patient and kidney outcomes than those with FSGS (log rank p<0.001). Cox regression analysis (adjusted for age) found that FSGS was significantly associated with death or kidney failure (adjusted hazard ratio 18.17, 95% confidence interval 2.28 -145.07, p=0.006), compared with MCD. Conclusion: Adults with severe primary podocytopathy due to FSGS had worse patient and kidney outcomes than MCD

Introductions: Patients with primary podocytopathies such as minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome are at risk for adverse outcomes. This study reports on the long -term outcomes, specifically kidney failure and death among patients treated for primary podocytopathies in a tertiary centre in Singapore. Materials and Methods: This was a single -centre, retrospective cohort study of all adults aged ≥21 years old diagnosed between 2016 and 2020 with MCD and FSGS with nephrotic -range proteinuria. We excluded patients with membranous nephropathy and secondary glomerulonephritides (lupus nephritis, ANCA - associated vasculitis, membranoproliferative glomerulonephritis, and diabetic nephropathy). Sociodemographic, comorbidity, laboratory and pharmacotherapy data were retrieved from the electronic medical records. The outcomes assessed were incidence of death or kidney failure (estimated glomerular filtration function [eGFR]<15 ml/min/1.73 m2 or required kidney replacement therapy). Results: Sixty patients (Chinese 80%, Malay 6%, Indian 3% and other races 3%) with MCD (37 patients) and FSGS (23 patients) were included. The morphological lesions in FSGS included cellular (n=2), tip (n=2), perihilar (n=7), collapsing (n=3) and not otherwise specified (n=17). At a median follow -up of 26.3 (8.9, 50.3) months, 12 (20%) outcomes were recorded, 11 (47.8%; death 6 and kidney failure 5) in the FSGS group and 1 (2.7%; died) in the MCD group. The causes of death were attributed to kidney failure (n=1), cardiovascular disease (n=1), infection (n=3); and unknown (n=2). The Kaplan -Meier survival curve showed that patients with MCD had better patient and kidney outcomes than those with FSGS (log rank p<0.001). Cox regression analysis (adjusted for age) found that FSGS was significantly associated with death or kidney failure (adjusted hazard ratio 18.17, 95% confidence interval 2.28 -145.07, p=0.006), compared with MCD. Conclusion: Adults with severe primary podocytopathy due to FSGS had worse patient and kidney outcomes than MCD

Introduction: Type 2 diabetes mellitus is a major healthcare problem worldwide, yet high percentage of patients are undiagnosed. There is a dire need for effective screening strategies. We examine the use of modified Asian FINDRISC (M-FINDRISC) and POCT random capillary blood glucose (rCBG) for the detection of dysglycemia Methodology: This cross-sectional, observational study included 151 adults aged ≥30 years without a prior history of diabetes in healthcare and community settings. Hemoglobin A1c of ≥6.3% was used for the diagnosis of diabetes, and 5.7– 6.2% for prediabetes. Areas under the receiver operating curve (ROC-AUC) for M-FINDRISC were analyzed. The sensitivity and specificity of the combined use of M-FINDRISC and rCBG for the detection of dysglycemia were evaluated. Results: The mean age of the participants was 44.6 ± 11.0 years. They had high body mass index (27.8 ± 4.9 kg/m²). Most were sedentary (only 25.2% reported physical activities of ≥30 min/day). A total of 52.3% had first-degree relatives with diabetes, but less than 12% were taking antihypertensive medication. Out of 151 participants, 3.3% (n = 5) were diagnosed with diabetes mellitus and 37.7% (n = 57) with prediabetes, giving an overall prevalence of 41.1% for dysglycemia. The mean age of participants with dysglycemia was significantly older (47.9 vs. 42.3 years, p-value 0.002). Other parameters were not statistically different for the two groups. Mean M-FINDRISC score was 9.7 ± 3.9 in the normal and 10.8 ± 4.0 in the dysglycemic group, while rCBG was 6.4 ± 1.1 mmol/L and 7.1 ± 3.1 mmol/L, respectively. ROC-AUC of M-FINDRISC for dysglycemia was 0.561. A combined screening strategy (M-FINDRISC score ≥7.5 and CBG ≥7.8 mmol/L) yielded high specificity (89.9%) but low sensitivity (17.7%) for dysglycemia. Conclusion While the combined screening strategy utilizing M-FINDRISC and POCT random CBG improves specificity, M-FINDRISC showed limited predictive value for dysglycemia in this specific cohort, making it a less ideal tool for screening.

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

This study aims to reveal the correlation between the pharmacokinetics(PK) and pharmacodynamics(PD) of multiple components in Epimedii Folium-Chuanxiong Rhizoma and clarify the pharmacodynamic material basis and mechanism of this herb pair in treating osteoarthritis. The Hulth method was used to establish the rat model of osteoarthritis and plasma was collected at various time points after drug administration. The plasma concentrations of multiple components were measured. Enzyme-linked immunosorbent assay(ELISA) was used to measure the plasma concentrations of matrix metalloproteinase(MMP)-3, MMP-13, interleukin-1β(IL-1β), nitric oxide(NO), and tumor necrosis factor-α(TNF-α) as pharmacodynamic indicators. Self-defined weighting coefficients were used to calculate the PK and PD data, and a Sigmoid E_(max) fitting model was used to evaluate the synergistic effect of the compatibility of Epimedii Folium-Chuanxiong Rhizoma. The PK-PD models for Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma were E=(1.926×C~(2.652))/(0.136 6~(2.652)+C~(2.652)), E=(1.618×C~(345.2))/(0.118 4~(345.2)+C~(345.2)), and E=(2.305×C~(2.786))/(0.240 3~(2.786)+C~(2.786)), respectively. The E_(max) of Epimedii Folium-Chuanxiong Rhizoma was larger than those of the two herbal medicines alone. The EC_(50) of the herb pair was lower than the sum of Epimedii Folium and Chuanxiong Rhizoma alone. The concentrations of MMP-3, MMP-13, IL-1β, NO, and TNF-α were correlated with mass concentrations of multiple components in Epimedii Folium and Chuanxiong Rhizoma, and the compatibility was better than single use. Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma may play a role in the treatment of osteoarthritis by inhibiting MMP-3, MMP-13, IL-1β, NO, and TNF-α.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Osteoarthritis/metabolism* ; Epimedium/chemistry* ; Interleukin-1beta/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Nitric Oxide/blood* ; Humans ; Rhizome/chemistry*

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVE To explore the early detection of large vestibular aqueduct syndrome(LVAS)in children by applying several audiological indicators.METHODS Ninety-two children with hearing loss(aged 1-70 months)were enrolled and divided into an LVAS group(45 cases)and a control group(47 cases).Eleven audiological indicators were statistically analyzed:lateral of hearing loss,the degree of hearing loss,configuration of hearing loss;ABR air-conduction threshold;ABR air-bone gap;ASSR average threshold;ASSR thresholds at 0.5,1,2,and 4 kHz;and tympanogram type.Indicators showing significant two-group differences were used to construct a visualized multifactorial linear prediction model using the R language.RESULTS Nine indicators demonstrated statistically significant differences between groups(P<0.05):laterality,configuration of hearing loss,ABR air-conduction threshold,ASSR average threshold,ASSR thresholds at all frequencies(0.5,1,2,4 kHz),and tympanogram type.A prediction model was established.When the total model score ranged between 200 and 240 points,the predicted LVAS risk probability was 0.1 to 0.99.The consistency index(C-index)was 0.85,indicating good predictive ability of the model.CONCLUSION The identified nine audiological indicators are valuable for the early detection of LVAS in children.The developed model can estimate LVAS risk.After refinement,this model holds potential to support early clinical diagnosis and intervention.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.