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1.
Toxicol Res ; 40(2): 285-295, 2024 Apr.
Article En | MEDLINE | ID: mdl-38525131

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.

2.
Open Life Sci ; 19(1): 20220812, 2024.
Article En | MEDLINE | ID: mdl-38465338

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.

4.
Magn Reson Imaging ; 108: 59-66, 2024 May.
Article En | MEDLINE | ID: mdl-38330724

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.


Adenocarcinoma , Brain Neoplasms , Carcinoma, Squamous Cell , Lung Neoplasms , Male , Humans , Middle Aged , Aged , Lung Neoplasms/diagnostic imaging , Protons , Amides , Magnetic Resonance Imaging/methods , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Carcinoma, Squamous Cell/diagnostic imaging
5.
Aging (Albany NY) ; 16(3): 2989-3006, 2024 Feb 06.
Article En | MEDLINE | ID: mdl-38329438

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.


Cognitive Dysfunction , NLR Family, Pyrin Domain-Containing 3 Protein , Mice , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Lipopolysaccharides/toxicity , Minocycline/pharmacology , Minocycline/therapeutic use , Interleukin-18 , Caspase 1/metabolism , Nigericin , bcl-2-Associated X Protein , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism
6.
BMC Nephrol ; 25(1): 68, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38408912

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.


Nephrotic Syndrome , Thromboembolism , Thrombosis , Child , Humans , Urokinase-Type Plasminogen Activator/therapeutic use , Nephrotic Syndrome/complications , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/chemically induced , Retrospective Studies , Hemorrhage/chemically induced , Thrombosis/etiology , Thrombosis/prevention & control , Anticoagulants/therapeutic use
7.
Article En | MEDLINE | ID: mdl-38211969

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN 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 analyzed 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 (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 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 to be 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.

8.
EClinicalMedicine ; 68: 102409, 2024 Feb.
Article En | MEDLINE | ID: mdl-38273888

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.

9.
Pediatr Res ; 95(4): 959-965, 2024 Mar.
Article En | MEDLINE | ID: mdl-38012310

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.


Endothelial Cells , Kidney Diseases , Mice , Animals , Endothelial Cells/metabolism , Receptor, TIE-2/metabolism , Vascular Cell Adhesion Molecule-1 , Fibrosis , Antibodies, Monoclonal/pharmacology , Kidney Diseases/chemically induced , Folic Acid , Inflammation , Angiopoietin-1 , Angiopoietin-2
10.
BMC Public Health ; 23(1): 2138, 2023 11 01.
Article En | MEDLINE | ID: mdl-37915007

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.


Cardiovascular Diseases , Copper , Adult , Humans , Causality , Nutrition Surveys , Prospective Studies , Risk Factors
11.
World J Pediatr ; 2023 Oct 19.
Article En | MEDLINE | ID: mdl-37853276

BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).

12.
Mol Biotechnol ; 2023 Sep 26.
Article En | MEDLINE | ID: mdl-37751128

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Ferroptosis is a new form of regulated cell death and targeting ferroptosis provides a novel therapeutic approach for human cancers. Verteporfin (VP) has been identified as a Yes-associated protein (YAP) inhibitor for treatment of several human cancers. However, it remains unclear whether VP exerts anticancer activity by inducing ferroptosis in ESCC cells. In the current study, we found that VP reduced cell viability and led to cell death in ESCC cell lines (KYSE150 and KYSE30) by inhibiting YAP expression. Subsequently, the findings revealed that VP treatment triggered significant ferroptosis events, including accumulation of Fe2+, reactive oxygen species (ROS) and malondialdehyde (MDA), reduction of mitochondrial membrane potential (MMP), glutathione (GSH) and glutathione peroxidase 4 (GPX4) expression. Further study showed that the effects of ESCC cell proliferation and death caused by VP could be reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Moreover, VP enhanced the chemosensitivity of ESCC resistant cells to paclitaxel (PTX). And VP combined with PTX can synergistically inhibit cell proliferation and induce cell death by triggering ferroptosis of PTX-resistant cells. All these data suggested that VP suppressed ESCC cell survival and reversed resistance to PTX through inducing ferroptosis, which may provide a promising therapeutic strategy for ESCC.

13.
Exp Ther Med ; 26(4): 491, 2023 Oct.
Article En | MEDLINE | ID: mdl-37753298

Subacute combined degeneration (SCD) is a neurological disorder caused by vitamin B12 deficiency, prevalent in the cervical and thoracic medullas, with an insidious onset and a lack of characteristic clinical manifestations. The present study describes a case of a 36-year-old female patient with SCD who demonstrated abnormal changes in the white matter of the brain. The laboratory test results showed a decrease in serum vitamin B12 levels and an increase in homocysteine levels. Magnetic resonance imaging (MRI) of the brain showed that, in addition to abnormal signals in the cervical and thoracic spine, speckled and short-striped abnormal signals were present, symmetrically distributed in the centrum semiovale. After 6 months of follow-up treatment, cranial MRI showed a significant attenuation of the symmetrical speckled and short-striped abnormal signals in the centrum semiovale. Homocysteine and serum vitamin B12 levels of the patient were within the expected range. Although, to the best of our knowledge, there have been no previous reports of alterations in the brain of patients with SCD, if these patients report neurological symptoms, clinicians should consider that these symptoms may be accompanied by inflammatory demyelination of the brain.

14.
Orphanet J Rare Dis ; 18(1): 297, 2023 09 22.
Article En | MEDLINE | ID: mdl-37736751

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration. METHODS: A retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children's Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated. RESULTS: Three patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0-23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment. CONCLUSION: Our data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.


Epstein-Barr Virus Infections , Lymphohistiocytosis, Hemophagocytic , Male , Child , Humans , Female , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/drug therapy , Herpesvirus 4, Human , Lymphohistiocytosis, Hemophagocytic/drug therapy , Programmed Cell Death 1 Receptor , Prospective Studies , Retrospective Studies
15.
Allergy Asthma Clin Immunol ; 19(1): 86, 2023 Sep 23.
Article En | MEDLINE | ID: mdl-37742016

BACKGROUND: Activated phosphoinositide3-kinase (PI3K) δ syndrome 1 (APDS1) is a novel inborn errors of immunity (IEIs) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD). APDS1 has a spectrum of clinical manifestations. Recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, hyper-IgM syndrome and autoimmunity are the common symptoms of this disease. CASE PRESENTATION: Patient 1 presented with recurrent respiratory infections, hepatosplenomegaly and hyper-IgM syndrome. Patient 2 developed early onset systemic lupus erythematosus (SLE)-like disease with resistant thrombocytopenia. c.3061 G > A and c.2314G > A variants in the PIK3CD gene were detected by whole exome sequencing in two patients respectively. c.2314G > A variant in PIK3CD gene of patient 2 is a newly report. After genetic diagnosis, two patients received sirolimus treatment and sirolimus alleviated clinical manifestations, including hepatosplenomegaly in patient 1 and thrombocytopenia in patient 2. CONCLUSION: Genetics diagnosis should be considered in patients with complicated clinical manifestations with no or insufficient response to the conventional therapies. If whole exome sequencing suggests a variant in PIK3CD gene, sirolimus may relieve hepatosplenomegaly and resistant thrombocytopenia. This is the first report of c.2314G > A variant in PIK3CD gene.

16.
Eur J Med Res ; 28(1): 355, 2023 Sep 19.
Article En | MEDLINE | ID: mdl-37726807

BACKGROUND: The triglyceride and glucose index (TyG), as a surrogate of insulin resistance (IR), is closely associated with non-alcoholic fatty liver disease (NAFLD). However, the association between the TyG index and NAFLD in atrial fibrillation (AF) is unknown. Therefore, the purpose of this study is to explore the association between the TyG index and NAFLD in AF. METHODS: This retrospective study was performed at Nanchang University's Second Affiliated Hospital. The AF patients who were hospitalized from January 2021 to December 2022 were enrolled. The association between the TyG index and NAFLD in AF patients was assessed by logistic regression and restricted cubic spline analysis. The ability of TyG index for identifying NAFLD was estimated by the area under the receiver operating characteristic (ROC). RESULTS: In this study, 632 people participated in the final analysis, with 176 (27.84%) having NAFLD. In the full adjustment model, there is an association between the TyG index and NAFLD [per 1 unit increment; odds ratios (ORs): 3.28; 95% confidence interval (CI) 2.14, 5.03]. Compared to the lowest tertile (TyG index < 8.29), the ORs for the highest tertile (TyG index ≥ 8.82) were 4.15 (95%CI: 2.28, 7.53). Dose-response analysis showed that the TyG index and NAFLD have a nearly linear relationship (P non-linear = 0.71). The area under the curve (AUC) of the TyG index is 0.735. CONCLUSIONS: Our findings showed a significant association between the TyG index and NAFLD. The TyG index may be a good marker for predicting NAFLD in AF patients.


Atrial Fibrillation , Non-alcoholic Fatty Liver Disease , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Retrospective Studies , Glucose , Triglycerides
17.
Front Pediatr ; 11: 1162974, 2023.
Article En | MEDLINE | ID: mdl-37456562

Background: Atypical hemolytic uremic syndrome (aHUS) with diacylglycerol kinase epsilon (DGKE) gene variant is a rare variant of thrombotic microangiopathy (TMA). The information on the clinical features, management and long-term outcomes of DGKE-aHUS patients have not yet been fully elucidated. The aim of this study was to report a novel variant of the DGKE gene in a Chinese population with aHUS. Case presentation: The present work reports a 7-month-old boy with aHUS, possibly triggered by gastrointestinal infection, without complement activation, with little response to plasma therapy and nephroprotective measures. The patient died during the 8th week of his hospital stay. The causes of death were intracranial hemorrhage and multiorgan dysfunction. Comprehensive WES of peripheral blood-derived DNA revealed two heterozygous variations in the DGKE exon region: NM_003647.2, c.610dup, p.Thr204Asnfs*4 and deletion of exons 4-6. Conclusions: This case suggest that atypical HUS with DGKE gene variant has a poor prognosis with a high mortality rate, which typically manifests in the first year of life and presents as a systemic disease with early-onset HUS with rapidly worsening renal function and chronic proteinuria. There is no specific treatment for DGKE-aHUS. There have an uncertain benefit of plasma therapy for DGKE-aHUS patients. The literature demonstrated that anti-complement therapy showed benefits for DGKE-aHUS with complement activation and autoantibodies during the overt TMA presentation but did not prevent TMA relapses. Early diagnosis and treatment may prevent complications and improve prognosis.

18.
Br J Nutr ; 130(12): 2114-2122, 2023 12 28.
Article En | MEDLINE | ID: mdl-37424297

Iodine is a vital trace element in the human body and is associated with several important coronary artery disease (CAD) risk factors. We aimed to explore the correlation between urinary iodine concentration (UIC) and CAD. Data from 15 793 US adults in the National Health and Nutrition Examination Survey (2003-2018) were analysed. We conducted multivariable logistic regression models and fitted smoothing curves to study the correlation between UIC and CAD. Furthermore, we performed subgroup analysis to investigate possible effect modifiers between them. We found a J-shaped association between UIC and CAD, with an inflection point at Lg UIC = 2·65 µg/l. This result indicated a neutral association (OR 0·89; 95 % CI 0·68, 1·16) between UIC and CAD as Lg UIC < 2·65 µg/l, but the per natural Lg [UIC] increment was OR 2·29; 95 % CI 1·53, 3·43 as Lg UIC ≥ 2·65 µg/l. An interaction between diabetes and UIC might exist. The increase in UIC results in an increase in CAD prevalence (OR 1·84, 95 % CI 1·32, 2·58) in diabetes but results in little to no difference in non-diabetes (OR 0·98, 95 % CI 0·77, 1·25). The J-shaped correlation between UIC and CAD and the interaction between diabetes and UIC should be confirmed in a prospective study with a series of UIC measurements. If excessive iodine precedes CAD, then this new finding could guide clinical practice and prevent iodine deficiency from being overcorrected.


Coronary Artery Disease , Diabetes Mellitus , Iodine , Adult , Humans , United States/epidemiology , Nutrition Surveys , Coronary Artery Disease/epidemiology , Coronary Artery Disease/chemically induced , Prospective Studies
19.
Materials (Basel) ; 16(11)2023 Jun 02.
Article En | MEDLINE | ID: mdl-37297281

Concrete-filled steel tube (CFST) columns have been widely used in residential buildings due to their high bearing capacity, good ductility, and reliable seismic performance. However, conventional circular, square, or rectangular CFST columns may protrude from the adjacent walls, resulting in inconvenience in terms of the arrangement of furniture in a room. In order to solve the problem, special-shaped CFST columns, such as cross-shaped, L-shaped, and T-shaped columns, have been suggested and adopted in engineering practice. These special-shaped CFST columns have limbs with the same width as the adjacent walls. However, compared with conventional CFST columns, the special-shaped steel tube provides weaker confinement to the infilled concrete under axial compressive load, especially at concave corners. The parting at concave corners is the key factor affecting the bearing capacity and ductility of the members. Therefore, a cross-shaped CFST column with steel bar truss stiffening is suggested. In this paper, 12 cross-shaped CFST stub columns were designed and tested under axial compression loading. The effects of steel bar truss node spacing and column-steel ratio on the failure mode, bearing capacity, and ductility were discussed in detail. The results indicate that the columns with steel bar truss stiffening can change the final deformation mode of the steel plate from single-wave buckling to multiple-wave buckling, and the failure modes of columns also subsequently change from single-section concrete crushing failure to multiple-section concrete crushing failure. The steel bar truss stiffening shows no obvious effect on the axial bearing capacity of the member but significantly improves the ductility. The columns with a steel bar truss node spacing of 140 mm can only increase the bearing capacity by 6.8% while nearly doubling the ductility coefficient from 2.31 to 4.40. The experimental results are compared with those of six design codes worldwide. The results show that the Eurocode 4 (2004) and the Chinese code CECS159-2018 can be safely used to predict the axial bearing capacity of cross-shaped CFST stub columns with steel bar truss stiffening.

20.
BMC Cardiovasc Disord ; 23(1): 294, 2023 06 10.
Article En | MEDLINE | ID: mdl-37301866

BACKGROUND: The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. METHODS: The Nation Health and Nutrition Examination Survey (NHANES) (2009-2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. RESULTS: This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation (r = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02-1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1-3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). CONCLUSIONS: Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.


Cardiovascular Diseases , Heart Failure , Insulin Resistance , Humans , Adult , Blood Glucose , Prevalence , Nutrition Surveys , Biomarkers , Glucose , Heart Failure/diagnosis , Heart Failure/epidemiology , Triglycerides
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