[Research progress on monogenic inherited glomerular diseases with central nervous system symptoms]. / ä¼´ä¸­æž¢ç¥žç»ç³»ç»Ÿç—‡çŠ¶çš„å•åŸºå› é—ä¼ æ€§è‚¾å°çƒç–¾ç— çš„ç ”ç©¶è¿›å±•.

To date, approximately 500 monogenic inherited kidney diseases have been reported, with more than 50 genes associated with the pathogenesis of monogenic isolated or syndromic nephrotic syndrome. Most of these genes are expressed in podocytes of the glomerulus. Neurological symptoms are common extrarenal manifestations of syndromic nephrotic syndrome, and various studies have found connections between podocytes and neurons in terms of morphology and function. This review summarizes the genetic and clinical characteristics of monogenic inherited diseases with concomitant glomerular and central nervous system lesions, aiming to enhance clinicians' understanding of such diseases, recognize the importance of genetic diagnostic techniques for comorbidity screening, and reduce the rates of missed diagnosis and misdiagnosis.

[Current clinical application of glomerular filtration rate assessment methods in pediatric populations]. / 肾小球滤过率评估方法在儿童人群中的应用现状.

Glomerular filtration rate (GFR) is a critical indicator of renal function assessment, which exhibits age-dependency in children and may differ from adults under various disease conditions. In recent years, there has been a growing focus on GFR among scholars, with an increasing number of clinical studies dedicated to refining and optimizing GFR estimation to span all pediatric age groups. However, the methods and assessment equations for estimating GFR may vary under different disease conditions, affecting the accuracy and applicability of assessments. This article reviews the peculiarities of renal function in children, explores GFR measurement methods, and evaluates the application of various GFR assessment equations in pediatric clinical practice, providing a reference for clinical assessment of renal function in children.

[Risk factors and prognosis of pediatric silent lupus nephritis with class â ¢ to â ¤]. / 儿童⠢~â ¤åž‹æ— ç—‡çŠ¶æ€§ç‹¼ç–®æ€§è‚¾ç‚Žçš„å±é™©å› ç´ åŠé¢„åŽåˆ†æž.

OBJECTIVES: To study the risk factors and prognostic characteristics of pediatric silent lupus nephritis (SLN) with class Ⅲ to V. METHODS: A retrospective study was conducted to collect clinical data from 30 children diagnosed with SLN at the Department of Pediatrics, Second Xiangya Hospital, Central South University, from May 2007 to April 2023. Based on renal pathological classification, the patients were divided into a class Ⅱ group (12 cases) and a class Ⅲ to Ⅴ group (18 cases). The risk factors for the occurrence of class Ⅲ to Ⅴ SLN were analyzed, and the prognostic characteristics were summarized. RESULTS: Among the 30 SLN patients, the median follow-up time was 61.50 months. There were no statistically significant differences in the proportions of patients who discontinued glucocorticoids or achieved low disease activity status, nor in the annual decline rate of estimated glomerular filtration rate (eGFR) between the class Ⅱ and class Ⅲ to V groups (P>0.05). However, three patients in the class Ⅱ group progressed to stage 1 chronic kidney disease (CKD), while eight patients in the class III to V group reached stage 1 CKD, and four patients reached stage 2 CKD. Among the 26 female SLN patients, serum complement C3 levels in the class III to V group were lower than those in the class Ⅱ group (P<0.05). Serum C3 levels in SLN patients, as well as in female SLN patients, were negatively correlated with the fluorescence intensity of IgA, IgG, and C3 immune complexes in the kidneys (P<0.05). Additionally, serum C3 levels in female SLN patients were negatively correlated with the renal pathological activity index (P<0.05). Binary logistic regression analysis indicated that being female and having low serum complement C3 levels were risk factors for the occurrence of class Ⅲ to V SLN in children (P<0.05). CONCLUSIONS: Class Ⅲ to V SLN is not uncommon among SLN children, and there remains a risk of long-term renal function progression. Being female and having low serum complement C3 levels are identified as risk factors for class Ⅲ to V SLN in children.

Emerging roles and therapeutic potentials of ferroptosis: from the perspective of 11 human body organ systems.

Since ferroptosis was first described as an iron-dependent cell death pattern in 2012, there has been increasing interest in ferroptosis research. In view of the immense potential of ferroptosis in treatment efficacy and its rapid development in recent years, it is essential to track and summarize the latest research in this field. However, few writers have been able to draw on any systematic investigation into this field based on human body organ systems. Hence, in this review, we provide a comprehensive description of the latest progress in unveiling the roles and functions, as well as the therapeutic potential of ferroptosis, in treating diseases from the aspects of 11 human body organ systems (including the nervous system, respiratory system, digestive system, urinary system, reproductive system, integumentary system, skeletal system, immune system, cardiovascular system, muscular system, and endocrine system) in the hope of providing references for further understanding the pathogenesis of related diseases and bringing an innovative train of thought for reformative clinical treatment.

Development and validation of a nomogram for predicting metabolic-associated fatty liver disease in the Chinese physical examination population.

AIM: We aim to develop and validate a nomogram including readily available clinical and laboratory indicators to predict the risk of metabolic-associated fatty liver disease (MAFLD) in the Chinese physical examination population. METHODS: The annual physical examination data of Chinese adults from 2016 to 2020 were retrospectively analyzed. We extracted the clinical data of 138 664 subjects and randomized participants to the development and validation groups (7:3). Significant predictors associated with MAFLD were identified by using univariate and random forest analyses, and a nomogram was constructed to predict the risk of MAFLD based on a Lasso logistic model. Receiver operating characteristic curve analysis, calibration curves, and decision curve analysis were used to verify the discrimination, calibration, and clinical practicability of the nomogram, respectively. RESULTS: Ten variables were selected to establish the nomogram for predicting MAFLD risk: sex, age, waist circumference (WC), uric acid (UA), body mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting plasma glucose (FPG), triglycerides (TG), and alanine aminotransferase (ALT). The nomogram built on the nonoverfitting multivariable model showed good prediction of discrimination (AUC 0.914, 95% CI: 0.911-0.917), calibration, and clinical utility. CONCLUSIONS: This nomogram can be used as a quick screening tool to assess MAFLD risk and identify individuals at high risk of MAFLD, thus contributing to the improved management of MAFLD.

Clustering of lifestyle behaviours and analysis of their associations with MAFLD: a cross-sectional study of 196,515 individuals in China.

BACKGROUND: The aggregation of lifestyle behaviours and their association with metabolic-associated fatty liver disease (MAFLD) remain unclear. We identified lifestyle patterns and investigated their association with the risk of developing MAFLD in a sample of Chinese adults who underwent annual physical examinations. METHODS: Annual physical examination data of Chinese adults from January 2016 to December 2020 were used in this study. We created a scoring system for lifestyle items combining a statistical method (multivariate analysis of variance) and clinical expertise (Delphi method). Subsequently, principal component analysis and two-step cluster analysis were implemented to derive the lifestyle patterns of men and women. Binary logistic regression analysis was used to explore the prevalence risk of MAFLD among lifestyle patterns stratified by sex. RESULTS: A total of 196,515 subjects were included in the analysis. Based on the defined lifestyle scoring system, nine and four lifestyle patterns were identified for men and women, respectively, which included "healthy or unhealthy" patterns and mixed patterns containing a combination of healthy and risky lifestyle behaviours. This study showed that subjects with an unhealthy or mixed pattern had a significantly higher risk of developing MAFLD than subjects with a relatively healthy pattern, especially among men. CONCLUSIONS: Clusters of unfavourable behaviours are more prominent in men than in women. Lifestyle patterns, as important factors influencing the development of MAFLD, show significant sex differences in the risk of MAFLD. There is a strong need for future research to develop targeted MAFLD interventions based on the identified behavioural clusters by sex stratification.

Causality of genetically determined metabolites on anxiety disorders: a two-sample Mendelian randomization study.

BACKGROUND: Although anxiety disorders are one of the most prevalent mental disorders, their underlying biological mechanisms have not yet been fully elucidated. In recent years, genetically determined metabolites (GDMs) have been used to reveal the biological mechanisms of mental disorders. However, this strategy has not been applied to anxiety disorders. Herein, we explored the causality of GDMs on anxiety disorders through Mendelian randomization study, with the overarching goal of unraveling the biological mechanisms. METHODS: A two-sample Mendelian randomization (MR) analysis was implemented to assess the causality of GDMs on anxiety disorders. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, whereas four different GWAS datasets of anxiety disorders were the outcomes. Notably, all datasets were acquired from publicly available databases. A genetic instrumental variable (IV) was used to explore the causality between the metabolite and anxiety disorders for each metabolite. The MR Steiger filtering method was implemented to examine the causality between metabolites and anxiety disorders. The standard inverse variance weighted (IVW) method was first used for the causality analysis, followed by three additional MR methods (the MR-Egger, weighted median, and MR-PRESSO (pleiotropy residual sum and outlier) methods) for sensitivity analyses in MR analysis. MR-Egger intercept, and Cochran's Q statistical analysis were used to evaluate possible heterogeneity and pleiotropy. Bonferroni correction was used to determine the causative association features (P < 1.03 × 10-4). Furthermore, metabolic pathways analysis was performed using the web-based MetaboAnalyst 5.0 software. All statistical analysis were performed in R software. The STROBE-MR checklist for the reporting of MR studies was used in this study. RESULTS: In MR analysis, 85 significant causative relationship GDMs were identified. Among them, 11 metabolites were overlapped in the four different datasets of anxiety disorders. Bonferroni correction showing1-linoleoylglycerophosphoethanolamine (ORfixed-effect IVW = 1.04; 95% CI 1.021-1.06; Pfixed-effect IVW = 4.3 × 10-5) was the most reliable causal metabolite. Our results were robust even without a single SNP because of a "leave-one-out" analysis. The MR-Egger intercept test indicated that genetic pleiotropy had no effect on the results (intercept = - 0.0013, SE = 0.0006, P = 0.06). No heterogeneity was detected by Cochran's Q test (MR-Egger. Q = 7.68, P = 0.742; IVW. Q = 12.12, P = 0.436). A directionality test conducted by MR Steiger confirmed our estimation of potential causal direction (P < 0.001). In addition, two significant pathways, the "primary bile acid biosynthesis" pathway (P = 0.008) and the "valine, leucine, and isoleucine biosynthesis" pathway (P = 0.03), were identified through metabolic pathway analysis. CONCLUSION: This study provides new insights into the causal effects of GDMs on anxiety disorders by integrating genomics and metabolomics. The metabolites that drive anxiety disorders may be suited to serve as biomarkers and also will help to unravel the biological mechanisms of anxiety disorders.

Analysis of the correlation between high iodized salt intake and the risk of thyroid nodules: a large retrospective study.

BACKGROUND: Currently, whether daily excess iodized salt intake increases the risk of thyroid nodules and even thyroid cancer remains controversial. Our research group aimed to provide a theoretical basis for the clinical guidance of daily iodized salt intake and the prevention of thyroid nodules through a retrospective analysis of the correlation between daily iodized salt intake and the risk of thyroid nodules and thyroid cancer in Hunan, China. METHODS: This study retrospectively analyzed the data of subjects who underwent a physical examination at the Health Management Center, Third Xiangya Hospital of Central South University, between January 1, 2017, and December 31, 2019. Subjects enrolled in this study underwent thyroid ultrasonography and tests to urine routines and liver and kidney function, and all subjects completed a questionnaire survey. The daily iodized salt intake of the study subjects was estimated based on spot urine methods (Tanaka). A multivariate logistic regression model was used to analyze the relationship between daily iodized salt intake and thyroid nodules and thyroid cancer. RESULTS: Among the 51,637 subjects included in this study, the prevalence of thyroid nodules was 40.25%, and the prevalence of thyroid cancer was 0.76%; among all enrolled subjects, only 3.59% had a daily iodized salt intake less than 5 g. In addition, we found that a daily intake of more than 5 g of iodized salt was not only an independent risk factor for the occurrence of thyroid nodules (odds ratio (OR): 2.08, 95% confidence interval (CI): 1.86-2.31, p < 0.001) but also an independent risk factor for the occurrence of thyroid cancer (OR: 5.81, 95% CI: 1.44-23.42, p = 0.012). A pooled analysis showed a significantly higher risk of thyroid nodules in subjects aged > 60 years with a daily iodized salt intake of more than 5 g compared to subjects aged < 60 years with a daily iodized salt intake of no more than 5 g (OR: 4.88, 95% CI: 4.29-5.54, p < 0.001); the risk of thyroid cancer was not significantly different between subjects aged > 60 years with a daily iodized salt intake of more than 5 g and those aged < 60 years with a daily iodized salt intake of no more than 5 g (OR: 2.15, 95% CI: 0.52-8.95, p = 0.281). The risk of thyroid nodules was not increased in physically active subjects with a daily iodized salt intake of more than 5 g compared to physically inactive subjects with a daily iodized salt intake of no more than 5 g (OR: 1.12, 95% CI: 0.97-1.28, p = 0.111). The same protective effect of physical activity was observed for thyroid cancer in subjects whose daily iodized salt intake exceeded 5 g. The risk of thyroid nodules was reduced for subjects with an education level of postgraduate and above, even when the daily iodized salt intake exceeded 5 g, compared to those with high school education and below and a daily iodized salt intake of no more than 5 g (OR: 0.79, 95% CI: 0.66-0.93, p = 0.005); however, a protective effect of education level on the occurrence of thyroid cancer was not observed. Independent risk factors affecting daily iodized salt intake greater than 5 g included age, triglycerides, family history of tumors, physical activity, and marital status. CONCLUSIONS: Daily intake of more than 5 g of iodized salt increased the risk of thyroid nodules and thyroid cancer, while increased physical activity and education level reduced the risk of thyroid nodules and thyroid cancer caused by iodized salt intake.

A novel biomimetic nanomedicine system with anti-inflammatory and anti-osteoporosis effects improves the therapy efficacy of steroid-resistant nephrotic syndrome.

Clinically, steroid-resistant nephrotic syndrome (SRNS) is always prolonged and difficult to treat and easily develops into end-stage renal disease, resulting in a low survival rate. Strategies to reverse steroid resistance and reduce the long-term use of high doses of steroid medicines are urgently needed. In this study, a novel nanoparticle drug system (Pm-GCH) with a core-shell structure was designed. Metal-organic frameworks, synthesized by glycyrrhizic acid (G) and calcium ions (Ca2+) loaded with hydrocortisone (H) were the core of the nanoparticles. Platelet membrane vesicles were the shells. The natural platelet membrane endows Pm-GCH with good biocompatibility and the ability to promote immune escape. In addition, under the chemotaxis of inflammatory factors, platelet membranes assist Pm-GCH in nonspecific targeting of the inflammatory sites of the kidney. Under an inflammatory acid environment, GCH slowly degrades and releases glycyrrhizic acid and hydrocortisone. Glycyrrhizic acid inhibits the inactivation of hydrocortisone, jointly inhibits the activity of phospholipase A2 (PLA2) and the classic activation pathway of complement C2, blocks the production of inflammatory factors, plays an anti-inflammatory role, and enhances the efficacy of hydrocortisone in the treatment of SRNS. Moreover, glycyrrhizic acid alleviates osteoporosis induced by long-term use of glucocorticoids. These results indicate that Pm-GCH is a promising treatment strategy for SRNS.

Is psychological flexibility a mediator between perceived stress and general anxiety or depression among suspected patients of the 2019 coronavirus disease (COVID-19)?

This study is aimed to investigate the status of general anxiety and depression among suspected patients of COVID-19 and explore whether psychological flexibility can serve as a mediator between perceived stress and general anxiety or depression. Total of 180 participants completed the online questionnaire which comprised demographic information, the Perceived Stress Scale (PSS), the 7-item Generalized Anxiety Disorder scale (GAD-7), the 9-item Patients Health Questionnaire (PHQ-9), the Acceptance and Action Questionnaire-II (AAQ-II) and the Cognitive Fusion Questionnaire (CFQ). Statistical methods including correlation analysis, multiple linear regression analysis and structural equation model were used in this study. The scores of 23.9% (43/180) and 34.4% (62/180) of participants were higher than the cut points of GAD-7 and PHQ-9 respectively. Psychological flexibility was significantly correlated with perceived stress, general anxiety and depression. Multiple regression analyses showed the possible mediation effect of psychological flexibility between perceived stress and general anxiety or depression. The structural equation model confirmed that psychological flexibility partially mediated between perceived stress and general anxiety or depression. Our findings suggested the potential benefit of Acceptance and Commitment Therapy (ACT) as a psychological support approach in suspected patients of COVID-19 because ACT targets psychological flexibility.

A novel likely pathogenic variant in the UMOD gene in a family with autosomal dominant tubulointerstitial kidney disease: a case report.

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by a pathogenic variant in UMOD (ADTKD-UMOD) is a rare group of diseases characterized by hyperuricaemia with decreased urinary excretion of urate, gout and progressive chronic kidney disease. The mundane clinical characteristics often result in a failure to diagnose ADTKD-UMOD. CASE PRESENTATION: In this report, we describe a 12-year-old boy who presented with polyarthritis, hyperuricaemia and tophi with a family history of 8 affected individuals. Clinical data, blood and urine samples of 3 affected members and 8 unaffected members were collected. Genetic testing of the eight genes (UMOD, HPRT1, PRPS1, MTHFR, REN, HNF1b, URAT1 and G6PC) was performed using Sanger sequencing. A heterozygous missense variant (c.674C > G; p.T225R) in UMOD was found in this boy, his older brother with the same phenotype and his mother with hyperuricaemia, gout and chronic kidney disease. CONCLUSION: This case highlights the importance of family history and genetic testing for definite diagnosis. This novel variant extends the spectrum of known UMOD gene variants and further supports the allelic heterogeneity of ADTKD-UMOD.

Podocytic infolding in Schimke immuno-osseous dysplasia with novel SMARCAL1 mutations: a case report.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive disorder characterized by spondyloepiphyseal dysplasia, progressive renal insufficiency and defective cellular immunity. Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity characterized by microspheres or microtubular structures associated with podocytes infolding into the glomerular basement membrane (GBM) on electron microscopy (EM). CASE PRESENTATION: A 4-year-old boy was admitted to our ward due to proteinuria and edema lasting 1 month. He had a short trunk and demonstrated subtle dysmorphology, with a triangular shape, a broad nasal bridge and a bulbous nasal tip. The laboratory findings were as follows: lymphocytes, 0.5 × 109/L; urine protein, 3.67 g/d; albumin, 9.8 g/L; and cholesterol, 11.72 mmol/L. Skeletal X rays showed small iliac wings, small ossification centers of the capital femoral epiphyses, shallow dysplastic acetabular fossae and mildly flattened vertebrae. The specimen for light microscopy (LM) suggested focal segmental glomerulosclerosis (FSGS). EM revealed a focal thickness of the GBM with some cytoplasmic processes of podocyte infolding into the GBM. Gene sequencing showed novel compound heterozygous mutations in the SMARCAL1 gene (c.2141 + 5G > A; c.2528 + 1G > A) that were inherited from his parents. Finally, we established the diagnosis of SIOD and treated him with diuretics and angiotensin-converting enzyme inhibitors (ACEIs). CONCLUSION: The pathogenic mechanism of PIG has not been clarified. Further studies are required to understand whether gene mutations, especially those related to podocytes, contribute to the pathogenesis of podocytic infolding.

[Effect of Homeobox A13 transfection on epithelial-mesenchymal transition and bone morphogenetic protein-7 expression in kidney tubular epithelial cells].

OBJECTIVE: To examine the transfection of Homeobox A13 (HOXA13) on epithelial-mesenchymal transition (EMT) and the expression of bone morphogenetic protein-7 (BMP-7) induced by albumin-overload in human kidney tubular epithelial cells (HKCs). METHODS: The cultured HKCs were treated with 20 mg/mL human serum albumin (HSA) for 48 hours. Protein expression of cytokeratin (CK), vimentin and HOXA13 in the HKCs was assessed by Western blot. Protein expression of CK, vimentin, and BMP-7 was also detected in HKCs transfected with lipofectamine contained HOXA13 DNA. RESULTS: HSA induced EMT in HKCs, presented by decreased CK expression (P<0.01) and increased vimentin expression (P<0.01). The up-regulated expression of HOXA13 transfected by lipofectamine inhibited the level of EMT induced by HSA in HKCs (P<0.05). The decreased rate of BMP-7 protein expression induced by HSA was inhibited by over-expressed HOXA13 in HKCs (P<0.05). CONCLUSIONS: Transfection of HOXA13 in HKCs could inhibit the degree of EMT induced by albumin-overload, possibly by increasing BMP-7 expression.

MME and PTPRC: key renal biomarkers in lupus nephritis.

Background: Lupus nephritis (LN) is an autoimmune-related kidney disease with a poor prognosis, however the potential pathogenic mechanism remains unclear and there is a lack of precise biomarkers. Therefore, a thorough screening and identification of renal markers in LN are immensely beneficial to the research on its pathogenic mechanisms and treatment strategies. Methods: We utilized bioinformatics to analyze the differentially expressed genes (DEGs) at the transcriptome level of three clusters: total renal, glomeruli, and renal tubulointerstitium in the GEO database to discover potential renal biomarkers of LN. We utilized NephroSeq datasets and measured mRNA and protein levels in the kidneys of MRL/lpr mice to confirm the expression of key DEGs. Results: Seven significantly differential genes (EGR1, MME, PTPRC, RORC, MX1, ZBTB16, FKBP5) were revealed from the transcriptome database of GSE200306, which were mostly enriched in the pathway of the hematopoietic cell lineage and T cell differentiation respectively by KEGG and GO analysis. The seven hot differential genes were verified to have consistent change trends using three datasets from NephroSeq database. The receiver operating characteristic (ROC) curve indicated that five DEGs (PTPRC, MX1, EGR1, MME and RORC) exhibited a higher diagnostic ROC value in both the glomerulus and tubulointerstitium group. Validation of core genes using MRL/lpr mice showed that MME and PTPRC exhibit significantly differential mRNA and protein expression patterns in mouse kidneys like the datasets. Conclusions: This study identified seven key renal biomarkers through bioinformatics analysis using the GEO and NephroSeq databases. It was identified that MME and PTPRC may have a high predictive value as renal biomarkers in the pathogenesis of LN, as confirmed by animal validation.

[Corrigendum] miR-382 inhibits migration and invasion by targeting ROR1 through regulating EMT in ovarian cancer.

Following the publication of the above article, an interested reader drew to the authors' attention that certain of the Transwell migration and invasion assay data panels shown in Figs. 3E and G and 7E and G on p. 1754 and 1757 respectively contained overlapping data panels, both within Fig. 3 and between Figs. 3 and 7, such that data which were intended to represent the results of differently performed experiments had apparently been derived from the same original sources. Specifically, the 'con' and 'pre-con' data panels in Fig. 3 were overlapping, as were the 'pre-con' and 'pcDNA.1-ROR1' panels comparing Fig. 3 with Fig. 7, and the Editorial Office subsequently pointed out to the authors that the 'con' and 'pre-con' data panels in Fig. 3E also contained an overlapping edge. After having examined their original data, the authors realized that these figures were inadvertently assembled incorrectly. The corrected versions of Figs. 3 and 7 are shown on the next page, now showing the correct data for the 'con' experiment in Fig. 3E, the 'pre-con' experiment in Fig. 3G, and the 'pcDNA.1-ROR1' panel in Fig. 7G. 'The authors are grateful to the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum, and all the authors agree with its publication; furthermore, they apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 48: 181-190, 2016; DOI: 10.3892/ijo.2015.3241].

Dose-Response Relationships of Moderate to Vigorous Physical Activity and Sedentary Time With Renal Function Indices in Adolescents With Reduced Renal Function: A Cross-Sectional Study.

BACKGROUND: This study aimed to explore the associations between moderate to vigorous physical activity (MVPA) and sedentary time with renal function indices in adolescents with kidney disease. METHODS: A cross-sectional study was conducted on 719 adolescents (median age 15 y, 40.6% female) with kidney disease from the National Health and Nutrition Examination Survey 2007-2016. The exposures were MVPA time and sedentary time. Renal metabolic parameters included serum uric acid (SUA), creatinine, blood urea nitrogen, the estimated glomerular filtration rate (eGFR), and the albumin creatinine ratio. Weighted multivariate regression analysis was used to estimate associations between exposures and outcomes. RESULTS: After stratifying MVPA time, the regression effect values ß (95% CI) for MVPA on SUA (Q2: -0.22 [-0.41 to -0.03]; Q3: -0.32 [-0.53 to -0.11]) and creatinine (Q2: -0.08 [-0.15 to -0.01]; Q3: -0.04 [-0.11 to 0.03]) gradually decreased with increasing MVPA time. In males (-0.76 [-1.19 to -0.32]), MVPA time was significantly associated with lower SUA levels compared with females (-0.14 [-0.38 to 0.10]). Notably, female adolescents who had an MVPA time exceeding 420 minutes exhibited lower albumin creatinine ratio (-75.37 [-146.63 to -4.11]). In addition, both recreational MVPA time (-0.26 [-0.45 to -0.06]) and sedentary time (-3.15 [-5.83 to -0.46]) were negatively associated with eGFR. CONCLUSIONS: Our study found an association between MVPA and lower levels of SUA in male adolescents with kidney disease and albuminuria in female adolescents with kidney disease. In addition, MVPA was also negatively associated with creatinine and eGFR, whereas sedentary time was only associated with eGFR. Further studies are needed to confirm these findings.

Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.

AIMS: Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms. METHODS: We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes. RESULTS: In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action. CONCLUSIONS: Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.

A new genetic diagnosis strategy for paroxysmal kinesigenic dyskinesia: Targeted high-throughput detection of PRRT2 gene c.649 locus.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most prevalent kind type of paroxysmal Dyskinesia, characterized by recurrent and transient episodes of involuntary movements. Most PKD cases were attributed to the proline-rich transmembrane protein 2 (PRRT2) gene, in which the c.649 region is a hotspot for known mutations. Even though some patients with PKD have been genetically diagnosed using whole-exome sequencing (WES) and Sanger sequencing, there are still cases of missed diagnoses due to the limitations of sequencing technology and analytic methods on throughput. METHODS: Patients meeting the diagnosis criteria of PKD with negative results of PRRT2-Sanger sequencing and WES were included in this study. Mutation screening and targeted high-throughput sequencing were performed to analyze and verify the sequencing results of the potential mutations. RESULTS: Six patients with PKD with high mutation ratios of c.649dupC were screened using our targeted high-throughput sequencing from 26 PKD patients with negative results of PRRT2-Sanger sequencing and WES (frequency = 23.1%), which compensated for the comparatively shallow sequencing depth and statistical flaws in this region. Compared with the local normal population and other patients with PKD, the mutation ratios of c.649dupC of these six patients with PKD were much higher and also had truncated protein structures and differentially altered mRNA expression. CONCLUSION: Based on the above studies, we emphasize the routine targeted high-throughput sequencing of the c.649 site in the PRRT2 gene in so-called genetic-testing-negative patients with PKD, and manually calculate the deletion and duplication mutations depth and ratios to lower the rate of clinical misdiagnosis.

[Expression of urinary neutrophil gelatinase-associated lipocalin and its clinical significance in children with idiopathic nephrotic syndrome].

OBJECTIVE: To investigate the urinary neutrophil gelatinase-associated lipocalin (NGAL) concentration in children with idiopathic nephrotic syndrome (INS) and its clinical significance. METHODS: Thirty-four children newly diagnosed with INS received oral prednisone for 4 weeks. Patients whose urinary protein did not become negative were classified as steroid-resistant nephrotic syndrome (SRNS) group, while those whose urinary protein did become negative were classified as steroid-sensitive nephrotic syndrome (SSNS) group. Morning midstream urine specimens were collected from all patients before use of prednisone and after 1, 2, 3, and 4 weeks of treatment with prednisone. Enzyme-linked immunosorbent assay was used to measure the urinary NGAL concentration. Meanwhile, urinary creatinine (Cr) concentration was measured, and urinary NGAL concentration in a single urine collection was adjusted according to the urinary Cr excretion. The two groups were compared in terms of urinary NGAL/Cr ratio. RESULTS: Compared with the SRNS group, the SSNS group had significantly decreased urinary NGAL/Cr ratios after 3 and 4 weeks of prednisone treatment (P < 0.05). Compared with the SRNS group, the SSNS group had a significantly decreased urinary ß2-MG/Cr ratio after 4 weeks of prednisone treatment (P < 0.05). In both groups, urinary NGAL/Cr ratio was positively correlated with urinary protein/Cr ratio (r = 0.510, P < 0.01). The results of ROC curve analysis showed when diagnostic cut-off point of urinary NGAL/Cr was 0.043 by 3 weeks after treatment, sensitivity and specificity achieved 100% and 79.2% respectively. CONCLUSIONS: Urinary NGAL/Cr ratio remains high in children with SRNS, while this ratio decreases gradually during prednisone treatment in children with SSNS, and it falls ahead of urinary ß2-MG/Cr ratio. These results suggest that dynamic monitoring of urinary NGAL/Cr ratio is useful for early judgment of response to prednisone in patients with INS.

Clinical features and familial mutations in the coexistence of Wilson's disease and Alport syndrome: A case report.

Background: Alport syndrome (AS) and Wilson's disease (WD) are genetic diseases that could lead to kidney damage. Herein, we report the clinical features and gene variants in a patient with WD and X-linked AS. Case presentation: The proband was a 12-year-old boy diagnosed with AS coexisting with WD at the age of 11 years. The patient underwent a medical check-up when he was 4 years and 8 months. Laboratory tests revealed elevated liver enzymes, decreased serum ceruloplasmin, increased 24-h urinary copper excretion, and one variant in the ATP7B gene. Then, the patient was diagnosed with WD. After 2 months of treatment with D-penicillamine and zinc salt, his liver function had recovered to normal levels, but he presented with microscopic hematuria. The hematuria did not resolve after switching to dimercaptosuccinic acid from D-penicillamine. In addition, he presented with proteinuria 3 years later. A renal biopsy was performed more than 6 years after the patient was diagnosed with WD, and electron microscopy showed that the basement membrane thickness was uneven, layered, and focal torn. Copper staining was negative. A genetic analysis identified a hemizygous variant (c.1718G > A, p. Gly573Asp) in COL4A5 and a homozygous variant (c.2975C > T, p. Pro992leu) in ATP7B. The patient's urine protein-creatinine ratio was less than 1.0 mg/mg after a 1 year of follow-up, after enalapril was administered for treating AS. Conclusion: This case highlights a lack of improvement in renal function after conventional treatment provides a possible indication for performing renal biopsy or genetic testing to determine the etiology in order to facilitate subsequent clinical management. Clinicians should prevent the occurrence of diagnostic inaccuracies caused by diagnostic anchoring because an accurate diagnosis is essential for achieving precise treatment and improved prognosis.