Clinical characteristics and outcomes of COVID-19 in pediatric patients with rheumatic diseases.

BACKGROUND: This study investigates the clinical characteristics and outcomes of pediatric patients with rheumatic diseases infected with COVID-19 in China. METHODS: We conducted a retrospective analysis of pediatric patients with rheumatic diseases who contracted COVID-19. Data were collected via a comprehensive questionnaire with a 14-day follow-up. Multivariable logistic regression was used to assess severe outcomes, and network analyses evaluated symptom correlations. RESULTS: A total of 1070 cases were collected. Fever (88.05%) and cough (62.75%) were the most common symptoms. Cough, nasal congestion, and runny nose exhibited a stronger correlation with each other. A higher incidence of fever reduced the incidence of two single symptoms (nasal congestion [r = -0.833], runny nose [r = -0.762]). Vaccinated children showed a shorter time to negative COVID-19 conversion (7.21 days vs. 7.63 days, p < 0.05) and lower hospitalization rates (p = 0.025). Prolonged symptom duration was associated with older age (OR: 1.07 [1.04-1.11]; p < 0.001) and systemic lupus erythematosus (OR: 1.47 [1.01-2.12]; p = 0.046). CONCLUSIONS: Pediatric patients with rheumatic diseases exhibited a wide range of clinical symptoms after COVID-19 infection. The infection generally did not lead to severe outcomes in this study. COVID-19 vaccination was associated with reduced hospitalization risk and expediting the time to negativity for virus. IMPACTS: This manuscript demonstrates a comprehensive analysis of the clinical characteristics and outcomes of COVID-19 infection in pediatric patients with rheumatic diseases in China. It provides critical insights into the specific challenges faced by this vulnerable population and offers practical recommendations for improving patient management during periods of increased infectious risk.

Evaluation of cucumber seed germination vigor under salt stress environment based on improved YOLOv8.

Seed germination vigor is one of the important indexes reflecting the quality of seeds, and the level of its germination vigor directly affects the crop yield. The traditional manual determination of seed germination vigor is inefficient, subjective, prone to damage the seed structure, cumbersome and with large errors. We carried out a cucumber seed germination experiment under salt stress based on the seed germination phenotype acquisition platform. We obtained image data of cucumber seed germination under salt stress conditions. On the basis of the YOLOv8-n model, the original loss function CIoU_Loss was replaced by ECIOU_Loss, and the Coordinate Attention(CA) mechanism was added to the head network, which helped the model locate and identify the target. The small-target detection head was added, which enhanced the detection accuracy of the tiny target. The precision P, recall R, and mAP of detection of the model improved from the original values of 91.6%, 85.4%, and 91.8% to 96.9%, 97.3%, and 98.9%, respectively. Based on the improved YOLOv8-ECS model, cucumber seeds under different concentrations of salt stress were detected by target detection, cucumber seed germination rate, germination index and other parameters were calculated, the root length of cucumber seeds during germination was extracted and analyzed, and the change characteristics of root length during cucumber seed germination were obtained, and finally the germination activity of cucumber seeds under different concentrations of salt stress was evaluated. This work provides a simple and efficient method for the selection and breeding of salt-tolerant varieties of cucumber.

Minocycline alleviates lipopolysaccharide-induced cardiotoxicity by suppressing the NLRP3/Caspase-1 signaling pathway.

Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1ß, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1ß, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro.

Eccentric Compression Behavior of Truss-Reinforced Cross-Shaped Concrete-Filled Steel Tubular Columns.

In the paper, the eccentric compression behavior of the truss-reinforced cross-shaped concrete-filled steel tubular (CCFST) column is investigated. A total of eighteen CCFST columns were tested under eccentric compression, and the key test variables included the reinforced truss node spacing (s = 140 mm and 200 mm), slenderness ratio (λ = 9.2, 16.6, and 23.1), and eccentricity ratio (η = 0, 0.08, and 0.15). The failure mode, deformation characteristic, stress distribution, strain distribution at the mid-span of the steel tube, and the eccentric compression bearing capacity were assessed. The results show that due to the addition of reinforced truss, the steel plates near the mid-span of eccentrically compressed CCFST columns experienced multi-wave buckling rather than single-wave buckling after the peak load was reduced to 85%, and the failure mode of concrete also changed from single-section to multi-section collapse failure. Comparisons were made with the unstiffened specimen. The ductility coefficient of the stiffened specimen with eccentricity ratios of 0.08-0.15 and node spacings of 140 mm~200 mm increased by 70~83%, approaching that of the multi-cell specimens with an increasing steel ratio of 1.8%. In addition, by comparing the test results with the calculation results of four domestic and international design codes, it was found that the Chinese codes CECS159-2018 and GB50936-2014, and the Eurocode 4 (2004) can be better employed to predict the compression bearing capacity of truss-reinforced CCFST columns.

Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications.

Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.

Anti-α-1,4-D-polygalacturonic acid antibodies as a new biomarker for juvenile idiopathic arthritis.

OBJECTIVE: Diagnosing juvenile idiopathic arthritis (JIA) is challenging. Our study aimed to investigate the clinical significance of anti-α-1,4-D-polygalacturonic acid (PGA) antibodies in JIA, focusing on their role in diagnosis and assessing disease activity. METHODS: In this prospective case-control study, we examined variations in serum levels of PGA-IgA and PGA-IgG among children with different types of JIA and healthy controls. Serum PGA-IgA and PGA-IgG levels were assessed concurrently in children with active and inactive JIA. RESULTS: This study included 126 patients diagnosed with JIA, 13 neonates, and 76 healthy children. Serum PGA-IgA and PGA-IgG levels were assessed, which revealed significant differences in PGA-IgA levels between various JIA subtypes and controls. An analysis of PGA-IgA levels in various JIA states revealed a statistically significant difference. Receiver operating characteristic (ROC) analysis demonstrated the robust predictive capability of PGA-IgA, with an AUC of 0.879 (p < 0.001), along with a specificity of 0.842 and sensitivity of 0.848. CONCLUSION: Increased levels of anti-PGA antibodies, particularly PGA-IgA, were significantly associated with JIA. PGA-IgA may serve as a sensitive biomarker for disease activity in JIA and could potentially aid in the diagnosis of JIA. Key Points • This study found a significant correlation between blood levels of PGA-IgA and juvenile idiopathic arthritis (JIA), which may provide valuable diagnostic insights. • PGA-IgA shows potential as a sensitive biomarker for the assessment of disease activity in JIA patients, helping to determine disease activity.

IQGAP1 overexpression attenuates chemosensitivity through YAP-mediated ferroptosis inhibition in esophageal squamous cell cancer cells.

Chemoresistance is one of the major hindrances to many cancer therapies, including esophageal squamous cell carcinoma (ESCC). Ferroptosis, a new programmed cell death, plays an essential role in chemoresistance. IQ-domain GTPase activating protein 1 (IQGAP1) is a scaffold protein and functions as an oncogene in various human malignancies. However, the underlying effect and molecular mechanisms of IQGAP1 on paclitaxel (PTX) resistance and ferroptosis in ESCC remain to be elucidated. In this study, we found that IQGAP1 was highly expressed in ESCC tissues and could as a potential biomarker for diagnosis and predicting the prognosis of ESCC. Functional studies revealed that IQGAP1 overexpression reduced the sensitivity of ESCC cells to PTX by enhancing ESCC cell viability and proliferation and inhibiting cell death, and protected ESCC cells from ferroptosis, whereas IQGAP1 knockdown exhibited contrary effects. Importantly, reductions of chemosensitivity and ferroptosis caused by IQGAP1 overexpression were reversed with ferroptosis inducer RSL3, while the increases of chemosensitivity and ferroptosis caused by IQGAP1 knockdown were reversed with ferroptosis inhibitor ferrostatin-1 (Fer-1) in ESCC cells, indicating that IQGAP1 played a key role in resistance to PTX through regulating ferroptosis. Mechanistically, we demonstrated that IQGAP1 overexpression upregulated the expression of Yes-associated protein (YAP), the central mediator of the Hippo pathway. YAP inhibitor Verteporfin (VP) could reverse the effects of IQGAP1 overexpression on ESCC chemoresistance and ferroptosis. Taken together, our findings suggest that IQGAP1 promotes chemoresistance by blocking ferroptosis through targeting YAP. IQGAP1 may be a novel therapeutic target for overcoming chemoresistance in ESCC.

Association between estimated glucose disposal rate and atrial fibrillation recurrence in patients undergoing radiofrequency catheter ablation: a retrospective study.

OBJECTIVE: Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. METHODS: This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 - (0.22 * body mass index) - (3.26 * hypertension) - (0.61 * HbA1c). Cox proportional hazard regression models and exposure-effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p < 0.01). Participants with an eGDR ≥ 8 mg/kg/min had a lower risk of AF recurrence than those with an eGDR < 4 mg/kg/min, with a hazard ratio (HR) of 0.28 [95% confidence interval (CI) 0.18, 0.42]. Additionally, restricted cubic spline analyses demonstrated a linear association between the eGDR and AF recurrence (p nonlinear = 0.70). The area under the curve (AUC) for predicting AF recurrence using the eGDR was 0.75. CONCLUSIONS: The study revealed that a decrease in the eGDR is associated with a greater AF recurrence risk after RFCA. Hence, the eGDR could be used as a novel biomarker for assessing AF recurrence risk.

Serum copper and obesity among healthy adults in the National Health and Nutrition Examination Survey.

BACKGROUND: Copper (Cu) homeostasis are important processes in the cause of metabolic diseases, but the association between Cu and obesity remains unclear. METHODS: Participants were drawn from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression assessed the associations of serum Cu concentrations (tertiles) with obesity and central obesity in individuals without comorbidities. Obesity was defined as a BMI ≥30.0 kg/m2, and central obesity was defined as a waist circumference ≥80 cm for women and ≥95 cm for men. RESULTS: This cross-sectional study included 1,665 adults without comorbidities, representing 24,744,034 people (mean age 35.1 years, 48.5% female). High serum Cu levels (tertile 3: ≥19.19 µmol/L) were associated with higher odds of obesity (adjusted odds ratio [OR]: 4.48, 95% CI[confidence interval]: 2.44-8.32) and central obesity (OR: 2.36, 95% CI: 1.19-4.66) compared to low serum Cu levels (tertile 1: ≤15.64 µmol/L). The dose-response curve showed a nonlinear association between Cu levels and obesity (P-nonlinear = 0.02) and a linear association with central obesity (P-nonlinear = 0.21). CONCLUSION: This study suggests that higher serum Cu levels are associated with increased odds of obesity in healthy American adults.

Nonlinear associations between the ratio of family income to poverty and all-cause mortality among adults in NHANES study.

Socioeconomic status (SES) has been linked to mortality rates, with family income being a quantifiable marker of SES. However, the precise association between the family income-to-poverty ratio (PIR) and all-cause mortality in adults aged 40 and older remains unclear. A cross-sectional study was conducted using data from NHANES III, including 20,497 individuals. The PIR was used to assess financial status, and various demographic, lifestyle, and clinical factors were considered. Mortality data were collected from the NHANES III linked mortality file. The study revealed a non-linear association between PIR and all-cause mortality. The piecewise Cox proportional hazards regression model showed an inflection point at PIR 3.5. Below this threshold, the hazard ratio (HR) for all-cause mortality was 0.85 (95% CI 0.79-0.91), while above 3.5, the HR decreased to 0.66 (95% CI 0.57-0.76). Participants with lower income had a higher probability of all-cause mortality, with middle-income and high-income groups showing lower multivariate-adjusted HRs compared to the low-income group. This study provides evidence of a non-linear association between PIR and all-cause mortality in adults aged 40 and older, with an inflection point at PIR 3.5. These findings emphasize the importance of considering the non-linear relationship between family income and mortality when addressing socioeconomic health disparities.

Correction: Li et al. Numerical Study on the Axial Compressive Behavior of Steel-Tube-Confined Concrete-Filled Steel Tubes. Materials 2024, 17, 155.

In the original publication [...].

n-Acetylcysteine protects against diazinon-induced histopathological damage and apoptosis in renal tissue of rats.

Diazinon (DZN) is a member of organophosphorus insecticides that has cytotoxic effects on different organs. n-Acetyl cysteine (NAC) is a widely used antioxidant in clinical, in vivo and in vitro studies. We evaluated the protective role of NAC against DZN-induced toxicity in kidney tissue of Wistar rats. 30 male Wistar rats were divided into 5 groups of control, single dose of DZN, continuous dose of DZN, single doses of DZN + NAC and continuous doses of DZN + NAC. Kidney function test (blood urea nitrogen, creatinine and uric acid) was provided. Levels of malondialdehyde (MDA), total antioxidant capacity (TAC) and total sulfhydryl (T-SH) were determined in renal tissues. Renal cells apoptosis was detected using TUNEL assay. The mRNA expressions of apoptosis, oxidative stress and inflammatory mediators, including B-cell lymphoma-2 (Bcl2), Bcl-2-associated X protein (Bax), superoxide dismutase (SOD), catalase (CAT), Interleukin 10 (IL-10), Tumor necrosis factor-α (TNF-α), Caspase-3 and Caspase-8 were analyzed in kidney tissues using Real Time PCR method. Chronic exposure to DZN was associated with severe morphological changes in the kidney, as well as impairment of its function and decreased kidney weights. Continues treatment with DZN significantly decreased the percentage of renal apoptotic cells as compared to rats treated with continuous dose of DZN alone (17.69 ± 3.67% vs. 39.46% ± 2.44%; p < 0.001). Continuous exposure to DZN significantly decreased TAC and T-SH contents, as well as SOD and CAT expression, but increased MDA contents in the kidney tissues (p < 0.001). A significant increase was observed in mRNA expression of Bax, Caspase-3, Caspase-8, as well as TNF-α following exposure to DZN, but the expression of IL-10 and Bcl2 was significantly decreased. NAC can protect kidney tissue against DZN-induced toxicity by elevating antioxidants capacity, mitigating oxidative stress, inflammation and apoptosis.

Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous.

Henoch-Schönlein purpura (HSP) and pediatric-onset systemic lupus erythematosus (pSLE) are closely associated with vasculitis and vascular diseases. This study aimed to investigate the clinical diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE. We surveyed 82 HSP patients, 34 pSLE patients, and 10 healthy children. The expression levels of Ang-1, Ang-2, and Tie2 in the serum and urine were assessed using enzyme-linked immunosorbent assay. The diagnostic values of Ang-1, Ang-2, and Tie2 for HSP and pSLE were evaluated using receiver operating characteristic curve analysis. The results revealed that the serum and urine expression levels of Ang-2 and Tie2 were significantly elevated in HSP and pSLE patients, whereas the Ang-1/Ang-2 values were reduced. Additionally, Ang-1 was highly expressed in the serum and urine of HSP patients and in the serum of pSLE patients. Ang-1, Ang-2, and Tie2 showed differential expression in various types of HSP and pSLE compared with their expression in healthy controls. In summary, Ang-1, Ang-2, and Tie2 can serve as biomarkers for HSP and pSLE. Moreover, Ang-1/Ang-2 values are reduced in HSP and pSLE patients. Ang-1, Ang-2, and Tie2 can be used as biomarkers for HSP and pSLE.

Minocycline alleviates LPS-induced cognitive dysfunction in mice by inhibiting the NLRP3/caspase-1 pathway.

BACKGROUND: Growing experimental evidence indicates that cognitive impairment is linked to neuroinflammation. Minocycline (MINO), an antibiotic known for its anti-inflammatory, has shown promise in alleviating cognitive impairment. Nonetheless, the exact mechanism through which MINO improves cognitive impairment is not yet understood. METHODS: A neuroinflammatory model was establish by utilizing lipopolysaccharide. The assessment of mice's cognitive and learning abilities was conducted through the MWM and Y-maze tests. The evaluation of hippocampal neuronal injury and microglial activation were achieved by performing HE staining and IHC, respectively. To evaluate BV2 cell viability and apoptosis, the CCK-8 and Hoechst 33342/PI staining assays were employed. In order to assess the protein and RNA expression levels of NLRP3, caspase-1, IL-1ß, IL-18, Iba-1, and Bcl2/Bax, WB and RT-qPCR were utilized. Additionally, the inhibitory effect of MINO on apoptosis by targeting the NLRP3/caspase-1 pathway was investigated using Nigericin. RESULTS: MINO was effective in reducing the time it took for mice to escape from the test, increasing the number of platforms they crossed, and mitigating damage to the hippocampus while also suppressing microglial activation and the expression of Iba-1 in a neuroinflammatory model caused by LPS. Furthermore, MINO improved the viability of BV2 cell and reduced apoptosis. It also had the effect of reducing the expression levels of NLRP3/Caspase-1, IL-1ß, IL-18, and BAX, while upregulating the expression of Bcl2. Additionally, MINO was found to downregulate the NLRP3 expression, which is specifically activated by nigericin. CONCLUSION: The protective effect of MINO relies on the crucial involvement of the NLRP3/caspase-1 pathway.

Amide proton transfer-weighted MRI in predicting pathological types of brain metastases in lung Cancer.

Most brain metastases originate from lung cancer. The majority of cases of lung cancer can be categorized into squamous carcinoma and adenocarcinoma,necessitating distinct clinical treatments and yielding diverse prognoses.Therefore,accurate preoperative evaluation of pathological types through imaging techniques is essential. The objective of this study is to assess the capability of amide proton transfer-weighted(APTw) MRI in predicting the pathological types of brain metastases in lung cancer.Additionally,it seeks to evaluate whether APTw MRI can provide additional value to diffusion-weighted imaging(DWI) at MRI·In this study,a total of 32 participants(mean age,60 ± 9 years;14 men) underwent evaluation,comprising 9 with squamous carcinoma and 23 with adenocarcinoma.Interestingly,adenocarcinoma demonstrated elevated APTw values(2.70 ± 0.81% vs 1.82 ± 0.47%;P = 0.001) and a higher apparent diffusion coefficient(ADC) value(1.00 ± 0.40 × 10-3 mm2/s vs 0.77 ± 0.13 × 10-3 mm2/s;P<0.05) in comparison to squamous carcinoma. The area under the receiver operating characteristic curve(AUC) of APTw and ADC in distinguishing between squamous carcinoma and adenocarcinoma were found to be 0.84 and 0.63,respectively.Moreover,the combined area under the receiver operating characteristic curve of the two techniques is 0.84. Amide proton transfer-weighted has the potential to predict the pathological types of brain metastases in lung cancer.

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study.

OBJECTIVE: To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. METHODS: A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children's Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. RESULTS: A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. CONCLUSION: The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Identification and validation of an explainable prediction model of acute kidney injury with prognostic implications in critically ill children: a prospective multicenter cohort study.

Background: Acute kidney injury (AKI) is a common and serious organ dysfunction in critically ill children. Early identification and prediction of AKI are of great significance. However, current AKI criteria are insufficiently sensitive and specific, and AKI heterogeneity limits the clinical value of AKI biomarkers. This study aimed to establish and validate an explainable prediction model based on the machine learning (ML) approach for AKI, and assess its prognostic implications in children admitted to the pediatric intensive care unit (PICU). Methods: This multicenter prospective study in China was conducted on critically ill children for the derivation and validation of the prediction model. The derivation cohort, consisting of 957 children admitted to four independent PICUs from September 2020 to January 2021, was separated for training and internal validation, and an external data set of 866 children admitted from February 2021 to February 2022 was employed for external validation. AKI was defined based on serum creatinine and urine output using the Kidney Disease: Improving Global Outcome (KDIGO) criteria. With 33 medical characteristics easily obtained or evaluated during the first 24 h after PICU admission, 11 ML algorithms were used to construct prediction models. Several evaluation indexes, including the area under the receiver-operating-characteristic curve (AUC), were used to compare the predictive performance. The SHapley Additive exPlanation method was used to rank the feature importance and explain the final model. A probability threshold for the final model was identified for AKI prediction and subgrouping. Clinical outcomes were evaluated in various subgroups determined by a combination of the final model and KDIGO criteria. Findings: The random forest (RF) model performed best in discriminative ability among the 11 ML models. After reducing features according to feature importance rank, an explainable final RF model was established with 8 features. The final model could accurately predict AKI in both internal (AUC = 0.929) and external (AUC = 0.910) validations, and has been translated into a convenient tool to facilitate its utility in clinical settings. Critically ill children with a probability exceeding or equal to the threshold in the final model had a higher risk of death and multiple organ dysfunctions, regardless of whether they met the KDIGO criteria for AKI. Interpretation: Our explainable ML model was not only successfully developed to accurately predict AKI but was also highly relevant to adverse outcomes in individual children at an early stage of PICU admission, and it mitigated the concern of the "black-box" issue with an undirect interpretation of the ML technique. Funding: The National Natural Science Foundation of China, Jiangsu Province Science and Technology Support Program, Key talent of women's and children's health of Jiangsu Province, and Postgraduate Research & Practice Innovation Program of Jiangsu Province.

Reduction of renal interstitial fibrosis by targeting Tie2 in vascular endothelial cells.

BACKGROUND: Tie2, a functional angiopoietin receptor, is expressed in vascular endothelial cells and plays an important role in angiogenesis and vascular stability. This study aimed to evaluate the effects of an agonistic Tie2 signal on renal interstitial fibrosis (RIF) and elucidate the underlying mechanisms. METHODS: We established an in vivo mouse model of folic acid-induced nephropathy (FAN) and an in vitro model of lipopolysaccharide-stimulated endothelial cell injury, then an agonistic Tie2 monoclonal antibody (Tie2 mAb) was used to intervent these processes. The degree of tubulointerstitial lesions and related molecular mechanisms were determined by histological assessment, immunohistochemistry, western blotting, and qPCR. RESULTS: Tie2 mAb attenuated RIF and reduced the level of fibroblast-specific protein 1 (FSP1). Further, it suppressed vascular cell adhesion molecule-1 (VCAM-1) and increased CD31 density in FAN. In the in vitro model, Tie2 mAb was found to decrease the expression of VCAM-1, Bax, and α-smooth muscle actin (α-SMA). CONCLUSIONS: The present findings indicate that the agonistic Tie2 mAb exerted vascular protective effects and ameliorated RIF via inhibition of vascular inflammation, apoptosis, and fibrosis. Therefore, Tie2 may be a potential target for the treatment of this disease. IMPACT: This is the first report to confirm that an agonistic Tie2 monoclonal antibody can reduce renal interstitial fibrosis in folic acid-induced nephropathy in mice. This mechanism possibly involves vascular protective effects brought about by inhibition of vascular inflammation, apoptosis and fibrosis. Our data show that Tie2 signal may be a novel, endothelium-specific target for the treatment of tubulointerstitial fibrosis.

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study.

BACKGROUND: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated. OBJECTIVE: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality. METHODS: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied. RESULTS: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25). CONCLUSION: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation.