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Background: Pregnancy-associated fulminant type 1 diabetes (PF) occurs during pregnancy or within 2 weeks of delivery. Although it occurs infrequently, it is associated with high fetal mortality rate. Few studies have examined whether PF is associated with gestational diabetes mellitus (GDM). Case Description: A 29-year-old woman diagnosed with GDM at 24 weeks of gestation developed a fever, sore throat, nausea and vomiting at 29 weeks of gestation. Ketoacidosis was considered based on her blood ketone and glucose levels and the results of a blood gas analysis. Since the patient's islet function declined rapidly, fluid replacement, insulin therapy, and other treatments were administered. The patient was ultimately diagnosed with PF, and has required ongoing insulin therapy. She delivered a healthy baby girl by elective cesarean section at 37-week gestation. Her blood glucose has been satisfactorily controlled over the 12 months since her acute presentation. Conclusions: PF is characterized by poor maternal and infant outcomes and a high stillbirth rate. Blood glucose should be regularly monitored in pregnant women with GDM. A sudden increase in blood glucose may indicate the possibility of PF, which needs to be managed in a timely manner to avoid adverse pregnancy outcomes.
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Diversion input lakes usually have a low catchment area/lake area ratio and pulsing pollution input. Various pollutants might accumulate in the lake continuously owing to the concentration effect under high evaporation but low precipitation over the entire area, typically for sedimentary cyclic elements such as phosphorus (P). However, the detailed transportation, sedimentation, and internal release mechanisms of P in the diversion input lakes remain unclear. This study conducted a year-long investigation of the littoral wetlands and open water areas of the shallow Lake Hengshui in the semi-humid region of North China. Results revealed that the average total P concentrations in the water and surficial sediment reached as high as 0.202 mg L-1 and 878.21 mg kg-1 in summer. The high water P levels in the lake were mainly regulated by the high internal P loading during summer and autumn, with the internal P loading being approximately nine times the external P loading. The littoral wetland area serves as a higher sedimentation sink and release source of P than the open water area. The concentrated P was continuously transported to the littoral wetland area through detritus burial, coprecipitation, and deposition of suspended particles. The release of P was mainly controlled by the dissolution of redox-sensitive Fe-P and Org-P at high temperatures and organic matter mineralization in the sediment, accompanied by the potential release capacity of apatite P (Ca-P). Future management of eutrophication and P levels in similar diversion input lakes should pay more attention to the high internal P loading in the sediment and the differentiated sedimentation and release processes in the littoral wetland and open water areas.
Subject(s)
Geologic Sediments , Lakes , Phosphorus , Wetlands , Phosphorus/analysis , China , Lakes/chemistry , Geologic Sediments/chemistry , Environmental Monitoring , Seasons , Water Pollutants, ChemicalABSTRACT
Foam dressing (FD) and micropower vacuum dressing (MVD) have been applied in the treatment of diabetic foot ulcer (DFU). However, research about the mode of action on the efficacy of the two dressings is extremely rare. This study proposed to explore the mechanism involved in diabetic wound healing under FD or MVD treatment. Macroscopical study was performed to evaluate the effectiveness of FD and MVD on wound healing in a rat model of DFU. Morphological analysis in the wound skin tissue was conducted by hematoxylin and eosin staining. Meanwhile, inflammatory cytokines in serum were measured by enzyme linked immunosorbent assay. The protein expression of phosphatidylinositol 3 kinase, protein kinase B and mammalian target of rapamycin (PI3K/AKT/mTOR) and their phosphorylation levels were determined by western blotting. We found that wound healing in rats with DFU was enhanced with the application of FD and MVD. The therapeutic efficacy of FD was superior to MVD. Compared with diabetic foot group, the concentrations of inflammatory cytokines, tumor necrosis factor alpha, interleukin-1ß and interleukin-6, were significantly down-regulated. Besides, the phosphorylation levels of PI3K, AKT and mTOR were up-regulated under FD or MVD treatment. We demonstrated that the treatment of FD and MVD effectively promoted the wound skin healing through activating the PI3K/AKT/mTOR pathway. Our research may provide a new idea for exploring the mode of action of dressing application in healing of DFU.
Subject(s)
Bandages , Diabetic Foot , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Rats, Sprague-Dawley , Signal Transduction , TOR Serine-Threonine Kinases , Wound Healing , Animals , TOR Serine-Threonine Kinases/metabolism , Diabetic Foot/therapy , Diabetic Foot/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Male , Phosphatidylinositol 3-Kinases/metabolism , Cytokines/metabolism , VacuumABSTRACT
Adrenocortical carcinoma (ACC) is a rare malignancy originating in the adrenal glands, aldosterone-producing ACC, even rarer. Papillary thyroid carcinoma (PTC), by contrast, accounts for the majority of thyroid carcinomas. We herein describe the first reported case of a female with comorbidities of aldosterone-producing ACC, PTC, and Graves' Disease(GD). The patient achieved transient clinical remission following adrenalectomy. However, three months later, aldosterone-producing ACC lung metastases emerged. Subsequently, within another three-month interval, she developed thyroid eye disease(TED). The patient died roughly one year after the adrenal operation. Exome sequencing did not reveal associations between aldosterone-producing ACC, PTC, and GD, and the underlying concurrence mechanism has yet to be elucidated. Further research of similar cases are needed to confirm potential links between the three pathologies.
Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Aldosterone , Graves Disease , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Female , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/genetics , Adrenocortical Carcinoma/metabolism , Adrenocortical Carcinoma/pathology , Graves Disease/metabolism , Graves Disease/complications , Graves Disease/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Adrenal Cortex Neoplasms/metabolism , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/complications , Aldosterone/metabolism , Middle Aged , Adrenalectomy , Fatal OutcomeABSTRACT
Kawasaki disease (KD) is a condition characterized by acute multi-system vasculitis and high fever in infants and children. Intravenous immunoglobulin (IVIG) is the established therapeutic approach of KD,foralleviating inflammation and mitigate the risk of arterial wall dilation and the development of coronary artery aneurysms (CAA). But almost 20% of the patients developed resistance to IVIG and displayed persistent fever after standard primary treatment. TSPAN5, belonging to the Tetraspanin family, has been demonstrated to modulate innate immunity in a range of human diseases. It accomplishes this by engaging with integrins and actively participating in the process of infection recognition. However, its relevance to susceptibility and IVIG therapy response of KD was unexposed. In the present study, our Integrative analysis of KD transcriptomic data and GTEx data revealed that the eQTL rs12504972 might modify the downregulation of TSPAN5 in KD patients. Moreover, our findings suggest a potential association between TSPAN5/rs12504972 and an elevated susceptibility as well as IVIG resistance among patients with Kawasaki disease in southern China. The results provided a new insight that TSPAN5 triggered KD susceptibility and resistance of IVIG therapy on the genomic level.
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OBJECTIVES: Diabetes mellitus has been a significant public health problem, associated with high rates of morbidity, disability, and mortality. Prediabetes is a crucial period for preventing and managing diabetes. 25(OH)D3 is an important risk factor for prediabetes. However, there is limited genetic knowledge of 25(OH)D3 in the Chinese population. This study was designed to identify genetic variants associated with 25(OH)D3 and explore the potential pathogenesis of prediabetes. METHODS: In this study, 451 individuals with prediabetes were recruited to determine the genetic variants associated with 25(OH)D3 through a genome-wide association study (GWAS). Gene mapping and overrepresentation analysis (ORA) were further performed to explore the candidate genes and their biological mechanisms. RESULTS: In this study, we identified two independent significant loci (rs9457733 and rs11243373, p < 5 × 10-6 and r2 < 0.6) and 37 candidate genes associated with 25(OH)D3 in prediabetes. Furthermore, the ORA analysis revealed that two genes in the gene sets, SLC22A1 and SLC22A3, were found to be significantly enriched in monoamine transmembrane transporter activity and quaternary ammonium group transmembrane transporter activity, as determined by WebGestalt and g:Profiler (padj < 0.05). CONCLUSION: The identification of potential genes associated with 25(OH)D3 provides a foundation for a better understanding of the pathogenesis, diagnosis, and treatment of prediabetes.
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Asian People , Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide , Prediabetic State , Humans , Prediabetic State/genetics , Female , Male , Middle Aged , Aged , China/epidemiology , Asian People/genetics , Adult , Calcifediol/blood , Organic Cation Transport Proteins/genetics , East Asian PeopleABSTRACT
This study aimed to investigate the associations between body mass index (BMI), waist circumference (WC), 25-hydroxy-vitamin D3 (25-OH-D3), and the risk of pre-diabetes mellitus (PDM), as well as their predictive values in identifying PDM. A total of 1688 participants were included in this cross-sectional investigation. Spearman's correlation analysis was used to assess the relationships between candidate indicators and PDM. The impact of indicators on PDM risk was determined by multivariate logistic regression. The receiver operating characteristic (ROC) analysis was performed to evaluate the prognostic value of indicators. Our study indicated a positive correlation between WC, BMI, and 25-OH-D3 and PDM. WC (OR = 1.05, 95% CI = 1.04-1.06, p < 0.001), BMI (OR = 1.11, 95% CI = 1.08-1.15, p < 0.001), and 25-OH-D3 (OR = 1.01, 95% CI = 1.00-1.02, p = 0.037) and an increased risk of PDM. Additionally, the ROC analysis demonstrated that WC (AUC = 0.651, Specificity = 55.00%, Sensitivity = 67.900%) had a higher diagnostic value for predicting PDM compared to the other variables (BMI, 25-OH-D3, TG, TC, LDL-C, HDL-C, and UA). A cut-off value of WC > 80.5 cm predicted PDM with both good sensitivity and specificity. Additionally, the cut-off value of waist circumference (WC) for men with prediabetes was 86.500, while for women with prediabetes, it was 76.500.
Subject(s)
Diabetes Mellitus , Prediabetic State , Male , Humans , Female , Body Mass Index , Waist Circumference , Risk Factors , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Cross-Sectional Studies , ROC Curve , China/epidemiologyABSTRACT
INTRODUCTION: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity. METHODS: Obesity was induced in Ube2L6AKO mice and age-matched Ube2L6flox/flox control mice by high-fat diet (HFD). Stromal vascular cells were isolated from the epididymal white adipose tissue of mice. Polarization induction was performed in mouse bone marrow-derived macrophages (BMDMs) by exposure to IFN-γ, lipopolysaccharide, or IL-4. F4/80 expression was assessed by immunohistochemistry staining. Expressions of M1/M2 macrophage markers and target molecules were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. Protein interaction was validated by co-immunoprecipitation (Co-IP) assay. The release of TNF-α and IL-10 was detected by ELISA. RESULTS: The polarization of pro-inflammatory M1 macrophages together with an increase in macrophage infiltration was observed in HFD-fed mice, which could be restrained by Ube2L6 knockdown. Additionally, Ube2L6 deficiency triggered the repolarization of BMDMs from M1 to M2 phenotypes. Mechanistically, Ube2L6 promoted the expression and activation of signal transducer and activator of transcription 1 (STAT1) through interferon-stimulated gene 15 (ISG15)-mediated ISGlylation, resulting in M1 macrophage polarization. CONCLUSION: Ube2L6 exerts as an activator of STAT1 via post-translational modification of STAT1 by ISG15, thereby triggering M1 macrophage polarization in HFD-fed obese mice. Overall, targeting Ube2L6 may represent an effective therapeutic strategy for ameliorating obesity-related T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Animals , Mice , Adipose Tissue/metabolism , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat/adverse effects , Inflammation/etiology , Inflammation/metabolism , Macrophages , Mice, Inbred C57BL , Mice, Obese , Obesity/etiology , Obesity/metabolismABSTRACT
Submerged plants constitute a vital component of shallow lake ecosystems, where water depth and sediment nitrogenphosphorus content are two key factors influencing their growth. This study focuses on Vallisneria natans and investigates the morphological and physiological changes of V. natans under the interaction of three water depth gradients and two different sediment nutrient levels. It explores the mechanisms through which varying sediment nutrient conditions under different water depths affect the growth of V. natans. The results indicate that both independent and interactive effects of water depth and sediment nutrient status significantly impact the morphology, antioxidant enzyme activity, and photosynthetic pigment content of V. natans, with water depth having a greater influence. To adapt to increased water depth-induced light stress, V. natans responds morphologically by increasing leaf length, leaf width, and decreasing maximum root length. Physiologically, it enhances its antioxidant regulation capacity and photosynthetic efficiency by increasing antioxidant enzyme activity, root vitality, and photosynthetic pigment content to counter weak light stress. However, these adaptations are insufficient to cope with excessively deep waters (200 cm). Sediment nutrient levels primarily control the growth of V. natans by affecting its root system. When sediment nitrogen and phosphorus content is lower, V. natans exhibits greater total root volume and surface area to enhance nutrient absorption efficiency. Water depth not only directly influences the growth of submerged plants but may also impact the migration and transformation of phosphorus in sediments, further exacerbating its effects on the growth of these plants, thus accelerating the regime shift of shallow lakes. Therefore, this study reveals V. natans' response strategies to varying water depths and sediment nutrient levels, determining suitable water levels and sediment nutrient conditions for its growth. These research findings provide a scientific basis for water level management and ecological restoration of submerged aquatic plants in shallow lakes.
Subject(s)
Ecosystem , Hydrocharitaceae , Water , Antioxidants , Hydrocharitaceae/physiology , Lakes , Nitrogen , Phosphorus , NutrientsABSTRACT
BACKGROUND: Formal risk assessment is crucial for diabetes prevention. We aimed to establish a practical nomogram for predicting the risk incidence of prediabetes and prediabetes conversion to diabetes. METHODS: A cohort of 1428 subjects was collected to develop prediction models. The LASSO was used to screen for important risk factors in prediabetes and diabetes and was compared with other algorithms (LR, RF, SVM, LDA, NB, and Treebag). Multivariate logistic regression analysis was used to construct the prediction model of prediabetes and diabetes, and drawn the predictive nomogram. The performance of the nomograms was evaluated by receiver-operating characteristic curve and calibration. RESULTS: These findings revealed that the other six algorithms were not as good as LASSO in terms of diabetes risk prediction. The nomogram for individualized prediction of prediabetes included "Age," "FH," "Insulin_F," "hypertension," "Tgab," "HDL-C," "Proinsulin_F," and "TG" and the nomogram of prediabetes to diabetes included "Age," "FH," "Proinsulin_E," and "HDL-C". The results showed that the two models had certain discrimination, with the AUC of 0.78 and 0.70, respectively. The calibration curve of the two models also indicated good consistency. CONCLUSIONS: We established early warning models for prediabetes and diabetes, which can help identify prediabetes and diabetes high-risk populations in advance.
Subject(s)
Diabetes Mellitus , Prediabetic State , Humans , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Incidence , Proinsulin , Diabetes Mellitus/epidemiology , Algorithms , Machine Learning , Nomograms , Retrospective StudiesABSTRACT
BACKGROUND: Primary aldosteronism (PA) is considered the number one aetiology for secondary hypertension. Apart from confirmatory tests and localisation of PA determined by computed tomography (CT), adrenal venous sampling (AVS) is used to define whether aldosterone hypersecretion occurs inside one or both adrenal glands. However, even correctly-performed AVS may lead to undiagnostic results such as apparent bilateral adrenal suppression (apparent bilateral aldosterone suppression), in which the adrenal aldosterone-to-cortisol ratios (AC ratios) are decreased bilaterally compared to the peripheral blood sample, with several causes contributing to it. CASE DESCRIPTION: Here, we describe the case of a 48-year-old man who was referred to our department for further investigation with a history of refractory hypertension, hypokalaemia, and aortic dissection. His hypertension and hypokalaemia were initially attributed to ectopic aldosteronoma due to his adrenal CT scan and AVS results. However, the correct diagnosis of an adenoma with duplicated right adrenal veins (duplicated adrenal veins) due to apparent bilateral aldosterone suppression was confirmed during surgery. CONCLUSION: AVS is the gold standard accepted for PA subtyping, but sometimes when apparent bilateral aldosterone suppression is present, it can give ambiguous results. Duplicated right adrenal veins, may impact results, thus, AVS may not accurately provide evidence of unilateral hypersecretion for all PA patients. Repeat AVS or adrenal surgery can provide worthwhile diagnostic conclusions.
The recognition and diagnosis of primary aldosteronism (PA) have increased in recent years and clinicians usually require adrenal venous sampling (AVS) to identify the affected side, and it's crucial for further treatments of PA patients (surgery or medicine).We presented an example of unilateral aldosteronoma with duplicated adrenal veins whose AVS results suggested apparent bilateral aldosterone suppression (the adrenal venous aldosterone/cortisol ratios are bilaterally lower than the peripheral ratios). He was misdiagnosed with ectopic aldosteronoma due to computed tomography (CT) features, but surgery findings revealed duplicated adrenal veins.Unclear AVS results such as apparent bilateral aldosterone suppression can lead to a missed diagnosis of unilateral PA, preventing patients from receiving potentially curative adrenal resection.Our case can serve as an example for clinicians that encounter the same condition to provide further investigational clues to ensure the correct aetiological diagnosis for patients with PA.
Subject(s)
Hyperaldosteronism , Hypertension , Hypokalemia , Male , Humans , Middle Aged , Aldosterone , Hyperaldosteronism/complications , Hyperaldosteronism/diagnosis , Hypokalemia/complications , Veins , Adrenal Glands/diagnostic imaging , Adrenal Glands/blood supply , Hypertension/complications , Diagnostic Errors/adverse effects , Retrospective StudiesABSTRACT
INTRODUCTION: Gestational diabetes mellitus (GDM) is considered an imbalance of glucose metabolism and insulin resistance during pregnancy. AIMS/OBJECTIVE: To evaluate the levels of periostin (POSTN) in patients with GDM and investigate the association between POSTN and GDM. MATERIALS AND METHODS: A total of 30 pregnant women (NC group) and 30 pregnant women with GDM (GDM group) were involved. The GDM mouse model was established by intraperitoneally injecting streptozotocin. The oral glucose tolerance test (OGTT), insulin, and insulin resistance indices were tested. An immunohistochemical and Western blot assay was conducted to determine the expression of POSTN, PPARα, TNF-α, and NF-κB. HE staining was performed to evaluate inflammation in the placental tissues of women with GDM and GDM mice. POSTN-siRNA was transfected into glucose-pretreated HTR8 cells, and pAdEasy-m-POSTN shRNA was infected in GDM mice. The RT-PCR assay determined the gene transcription of POSTN, TNF-α, NF-κB, and PPARα. RESULTS: Pregnantwomen in theGDMgroup demonstrated significantly higherOGTT (p < 0.05), insulin levels (p < 0.05) and insulin resistance (p < 0.05) compared to those of the NC group. The serum levels of POSTN in pregnantwomen of theGDMgroup were significantly higher than that of theNC group (p < 0.05). The obvious inflammation was activated in pregnant women in the GDMgroup. POSTN-siRNAsignificantly enhanced the cell viability of glucose-treated HTR8 cells compared to that without glucose treatment (p < 0.05). POSTNsiRNA (pAdEasy-m-POSTN shRNA) markedly reduced the glucose level of glucose-treated HTR8 cells (GDM mice) compared to that without treatment (p < 0.05). POSTN-siRNA (pAdEasy-m-POSTN shRNA) promoted PPARα gene transcription (p < 0.05) and inhibited NF-κB/TNF-α gene transcription (p < 0.05) in glucose-treated HTR8 cells (GDMmice) compared to thosewithout treatment. POSTN-siRNAmodulated NF- κB/TNF-α pathway mediated inflammation by regulating PPARα in HTR8 cells and GDMmice. PPARα participated in POSTN-associated inflammation. pAdEasy-m-POSTN shRNA inhibited T-CHO/TG levels in GDM mice compared to those without treatment (p < 0.05). All the effects of POSTN-siRNA (pAdEasy-m- POSTN shRNA) were obviously blocked by PPARα inhibitor treatment. CONCLUSION: POSTN levels were significantly higher in pregnant women with GDM and were associated with chronic inflammation and PPARα expression. POSTN may act as a bridge between GDM and chronic inflammation to modulate insulin resistance by modulating PPARα/NF-κB/TNF-α signaling pathway.
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Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting infants and children. Activated platelets predispose patients to coronary artery structural lesions that may lead to thrombotic cardiovascular events. To discover potential proteins underlying platelet activation in KD, we conducted a protein chip assay of 34 cytokines and discovered thymic stromal lymphopoietin (TSLP) was aberrantly expressed, which remained elevated after intravenous immunoglobulin G (IVIG) treatment and during convalescence in KD patients in comparison to healthy controls. Enzyme-linked immunosorbent assay (ELISA) corroborated the upregulation of TSLP in KD patients, which was exacerbated in convalescent patients complicated with thrombosis. TSLP receptors on platelets were also significantly upregulated in KD patients complicated with thrombosis. Platelet activation, apoptosis, and mitochondrial autophagy (mitophagy) were increased in convalescence KD patients complicated with thrombosis. In vitro, TSLP induced platelet activation and platelet mitophagy in healthy blood donors, as observed in KD patients. TSLP, similar to mitophagy agonist carbonyl cyanide 3-chlorophenyl hydrazone (CCCP), promoted thrombosis, which was attenuated by the mitophagy inhibitor Mdivi-1. Co-immunoprecipitation in TSLP-treated platelets revealed TSLP receptor (TSLPR) bound to mitophagy regulators, Parkin and Voltage Dependent Anion Channel Protein 1 (VDAC1).Thus, our results demonstrated that TSLP induced platelet mitophagy via a novel TSLPR/Parkin/VDAC1 pathway that promoted thrombosis in KD. These results suggest TSLP as a novel therapeutic target against KD-associated thrombosis.
Subject(s)
Blood Platelets , Mucocutaneous Lymph Node Syndrome , Infant , Child , Humans , Blood Platelets/metabolism , Thymic Stromal Lymphopoietin , Mitophagy , Mucocutaneous Lymph Node Syndrome/therapy , Convalescence , Cytokines/metabolism , Ubiquitin-Protein Ligases/metabolismABSTRACT
Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis affecting infants and young children. A high dose of intravenous immunoglobulin (IVIG) is the first-line strategy for patients with KD to reduce persistent inflammation and the risk of coronary artery aneurysm (CAA) formation. Unfortunately, 10-20% of the patients showed no response to the treatment and were defined as resistant to IVIG. Rab31 has been reported to regulate innate immunity in several human diseases. However, whether single nucleotide polymorphism (SNP) in Rab31 gene could predispose to IVIG therapy response in KD was uncovered. Methods: Rab31/rs9965664 polymorphism was genotyped in 1,024 Chinese patients with KD through TaqMan assay. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between Rab31/rs9965664 polymorphism and IVIG therapeutic effects. Results: Our results showed that Rab31/rs9965664 AA/GA genotype was significantly associated with an increased risk of IVIG resistance compared to GG genotype (GA vs. GG: p = 0.0249; AA vs. GG: p = 0.0016; AA/GA vs. GG: p = 0.0039; and AA vs. GG/GA: p = 0.0072). Moreover, the KD individuals carrying the rs9965664 A allele displayed lower Rab31 protein levels, and the expression level of Rab31 in the IVIG-resistant group was decreased significantly when compared to that observed in the response group. A mechanical study demonstrated that Rab31 modulated IVIG response through NLRP3 and p38 pathways. Conclusion: These results suggested that Rab31/rs9965664 polymorphism might be associated with an increased risk of IVIG resistance in southern Chinese patients with KD. The possible mechanism is that Rab31 regulates the NLRP3 pathway negatively to inhibit IVIG response.
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Background: Sepsis is a severe systemic reaction disease induced by bacteria and virus invading the bloodstream and subsequently causing multiple systemic organ dysfunctions. For example, the kidney may stop producing urine, or the lungs may stop taking in oxygen. Recent studies have shown that long non-coding RNAs (lncRNAs) are related to the dysfunction of organs in sepsis. This study aims to screen and validate the sepsis-associated lncRNAs and their functional single nucleotide polymorphisms (SNPs). Result: Unconditional multiple logistic regression based on the recessive model (adjusted odds ratio = 2.026, 95% CI = 1.156-3.551, p = 0.0136) showed that patients with the CC genotype of rs579501 had increased risk of sepsis. Stratification analysis by age and gender indicated that patients with the rs579501 CC genotype had higher risk of sepsis among children aged <12 months (adjusted odds ratio = 2.638, 95% CI = 1.167-5.960, p = 0.0197) and in male patients (adjusted odds ratio = 2.232, 95% CI = 1.127-4.421, p = 0.0213). We also found a significant relationship between rs579501 and severe sepsis risk (CC versus AA/AC: adjusted odds ratio = 2.466, 95% CI = 1.346-4.517, p = 0.0035). Stratification analysis for prognosis and number of organ dysfunctions demonstrated that the rs579501 CC genotype increased non-survivors' risk (adjusted odds ratio = 2.827, 95% CI = 1.159-6.898, p = 0.0224) and one to two organs with dysfunction risk (adjusted odds ratio = 2.253, 95% CI = 1.011-5.926, p = 0.0472). Conclusion: Our findings showed that the lnc-ZNF33B-2:1 rs579501 CC genotype increases the susceptibility to sepsis. From the medical perspective, the lnc-ZNF33B-2:1 rs579501 CC genotype could be serving as a biochemical marker for sepsis.
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BACKGROUND: Gestational diabetes mellitus (GDM) refers to abnormal glucose tolerance during pregnancy, and it is often accompanied by obvious changes in glucose and lipid metabolism, and associated with adverse pregnancy outcomes. The incidence of fetal distress, polyhydramnios, puerperal infection, premature delivery, and macrosomia in pregnant women with GDM are higher than in those without GDM. AIM: To analyze the relationship between age of pregnant women with GDM and mode of delivery and neonatal Apgar score. METHODS: A total of 583 pregnant women with GDM who delivered in the Department of Obstetrics at our hospital between March 2019 and March 2022 were selected. Among them, 377 aged < 35 years were selected as the right age group and 206 aged > 35 years were selected as the older group. The clinical data of the two groups were collected, and the relationship between age of the pregnant women with GDM and mode of delivery, maternal and neonatal outcomes, and neonatal Apgar score were compared. In the older group, 159 women were classed as the adverse outcome group and 47 as the good outcome group according to whether they had adverse maternal and infant outcomes. The related factors of adverse maternal and infant outcomes were analyzed through logistic regression. RESULTS: The number of women with assisted pregnancy, ≤ 37 wk gestation, ≥ 2 pregnancies, one or more deliveries, and no pre-pregnancy blood glucose screening in the older group were all higher than those in the right age group (P < 0.05). The natural delivery rate in the right age group was 40.85%, which was higher than 22.33% in the older group (P < 0.05). The cesarean section rate in the older group was 77.67%, which was higher than 59.15% in the right age group (P < 0.05). The older group had a higher incidence of polyhydramnios and postpartum hemorrhage, and lower incidence of fetal distress than the right age group had (P < 0.05). There was no significant difference in neonatal weight between the two groups (P > 0.05). The right age group had higher Apgar scores at 1 and 5 min than the older group had (P < 0.05). Significant differences existed between the poor and good outcome groups in age, education level, pregnancy mode, ≤ 37 wk gestation, number of pregnancies, and premature rupture of membranes (P < 0.05). Logistic regression showed that age, education level and premature rupture of membranes were all risk factors affecting the adverse outcomes of mothers and infants (P < 0.05). CONCLUSION: Delivery mode and Apgar score of pregnant women with GDM are related to age. Older age increases the adverse outcome of mothers and infants.
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In shallow lakes, eutrophication leads to a shift of the macrophyte-dominated clear state towards an algae-dominated turbid state. Phosphorus (P) is a crucial element during this shift and is usually concentrated in the suspended particulate matter (SPM) in water. However, the dominant processes controlling internal P release in the algae- (ADA) and macrophyte-dominated (MDA) areas under the influence of P-concentrated SPM remains unclear. In this study, we conducted monthly field observations of P exchange across the sediment-water interface (SWI) with the deposition of SPM in the ADA and MDA of Lake Taihu. Results revealed that both algae- and macrophyte-originated SPM led to the depletion of oxygen across the SWI during summer and autumn. Redox-sensitive P (Fe-P) and organic P (Org-P) were the dominant mobile P fractions in both areas. High fluxes of P across the SWI were observed in both areas during the summer and autumn. However, the processes controlling P release were quite different. In MDA, P release was mostly controlled by a traditional Fe-P dissolution process influenced by the coupled cycling of iron, sulfur, and P. In the ADA, Org-P control was intensified with the deterioration of algal bloom status, accompanied with the dissolution of Fe-P. Evidence from the current study revealed that the dominant process controlling the internal P release might gradually shift from Fe-P to a coupled process of Fe-P and Org-P with the shift of the macrophyte- to an algae-dominated state in shallow eutrophic lakes. The differentiated processes in the MDA and ADA should be given more attention during future research and management of internal P loadings in eutrophic lakes.
Subject(s)
Phosphorus , Water Pollutants, Chemical , China , Environmental Monitoring/methods , Eutrophication , Geologic Sediments , Iron , Lakes , Oxygen , Particulate Matter/analysis , Phosphorus/analysis , Sulfur , Water , Water Pollutants, Chemical/analysisABSTRACT
INTRODUCTION: Fasting proinsulin (FPI) and fasting insulin (FI) have been demonstrated to be associated with impaired b cell function, T2DM, and insulin resistance. This genome-wide association study (GWAS) was performed to contribute to our understanding of the genetic basis of FPI, FI, 2-hour postprandial proinsulin (2hPI), and 2-hour postprandial insulin (2hI) of the pathophysiology of prediabetes in the Chinese population. MATERIAL AND METHODS: The levels of fasting plasma glucose (FPG), FPI, FI, 2hPI, and 2hI were examined by an automatic biochemical analyser. The Applied BiosystemsTM AxiomTM Precision Medicine Diversity Array, the Gene Titan Multi-Channel instrument, and Axiom Analysis Suite 6.0 Software were used for genotyping. Imputation was performed with IMPUTE 2.0 software from HapMap, 1000 Genomes Phase 3 as a reference panel. RESULTS: Six single nucleotide polymorphisms (SNPs) in DLG1-AS1, SORCS1, and CTAGE11P for FPI, and 27 SNPs in ZNF718, MARCHF2, and HNRNPM for 2hPI reached genome-wide significance. Genome-wide significance was reached for associations of 6 SNPs in KRT71 to FI. Also, 14 SNPs in UBE2U, ABO, and GRID1-AS1 were genome-wide significant in their relationship with 2hI. Among these, the genetic loci of CTAGE11P, MARCHF2, KRT71, and ABO have the strongest association with FPI, 2hPI, FI, and 2hI. CONCLUSIONS: The genetic variants of CTAGE11P, MARCHF2, KRT71, and ABO are significantly correlated with FPI, 2hPI, FI, and 2hI, respectively, in Chinese Han people. These genetic variants may serve as new biomarkers for the prevention of prediabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Prediabetic State , Humans , Blood Glucose , Diabetes Mellitus, Type 2/genetics , East Asian People , Fasting , Genome-Wide Association Study , Insulin/blood , Proinsulin/bloodABSTRACT
Background: Kawasaki disease (KD) is an acute, self-limited vasculitis disorder of unknown etiology in children. Immunologic abnormalities were detected during the acute phase of KD, which reflected that the effect cells of the activated immune system markedly increased cytokine production. High-dose intravenous immunoglobulin (IVIG) therapy is effective in resolving inflammation from KD and reducing occurrence of coronary artery abnormalities. However, 10%-20% of KD patients have no response to IVIG therapy, who were defined as IVIG resistance. Furthermore, these patients have persistent inflammation and increased risk of developing coronary artery aneurysm (CAA). EIF2AK4 is a stress sensor gene and can be activated by pathogen infection. In addition, the polymorphisms of EIF2AK4 were associated with various blood vessel disorders. However, it remains unclear whether the EIF2AK4 gene polymorphisms were related to IVIG therapy outcome in KD patients. Methods: EIF2AK4/rs4594236 polymorphism was genotyped in 795 IVIG response KD patients and 234 IVIG resistant KD patients through TaqMan, a real-time polymerase chain reaction. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association between EIF2AK4/rs4594236 polymorphism and IVIG therapeutic effects. Results: Our results showed that the EIF2AK4/rs4594236 AG/GG genotype was significantly associated with increased risk to IVIG resistance compared to the AA genotype (AG vs. AA: adjusted ORs = 1.71, 95% CIs = 1.17-2.51, and p = 0.0061; GG vs. AA: adjusted ORs = 2.09, 95% CIs = 1.36-3.23, and p = 0.0009; AG/GG vs. AA: adjusted ORs = 1.82, 95% CIs = 1.27-2.63, and p = 0.0013; and GG vs. AA/AG: adjusted ORs = 1.45, 95% CI = 1.04-2.02, and p = 0.0306). Furthermore, the stratified analysis of age and gender in the KD cohort indicated that male patients carrying the rs4594236 AG/GG genotype tends to be more resistant to IVIG therapy than female patients. Conclusion: These results suggested that EIF2AK4/rs4594236 polymorphism might be associated with increased risk of IVIG resistance in southern Chinese KD patients.
ABSTRACT
Background: In recent years, the incidence of thyroid diseases has increased significantly, which has seriously affected people's work and life. The purpose of this study was to explore the epidemiological characteristics of thyroid diseases and autoantibodies. Method: According to the principle of overall sampling, resident residents ≥18 years and who will not move within 5 years are randomly selected. A total of 2136 eligible individuals were divided into case and control groups according to whether they have thyroid disease. Finally, the impact of potential risk factors on thyroid diseases was evaluated. Results: The overall prevalence of thyroid disease was 58.3%, and there was a significant difference in the prevalence of thyroid disease between women and men (p = 0.004). Except for the age group ≥70 years, with the increase in age, the prevalence gradually increased (p < 0.05). Participants with positive thyroid autoantibodies (TPOAb or TgAb) had a higher prevalence than participants with negative autoantibodies. The positive rate of autoantibodies in women was higher than that in men (p < 0.05). UIC (p = 0.004) and free thyroid hormone (FT4) (p = 0.001) levels of men were higher than those of women, and the TSH level of women was higher than that of men (p = 0.002). The regression analysis showed that women, older age, and family history of thyroid disease were independent risk factors for thyroid disease. Conclusion: The prevalence of thyroid diseases in Hainan was high. Women are more susceptible to thyroid disease than men, and the prevalence increased with age.