A risk prediction model of gestational diabetes mellitus based on traditional and genetic factors.

BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication during pregnancy. We aimed to evaluate a risk prediction model of GDM based on traditional and genetic factors. METHODS: A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to gather general data. Serum test results were collected from the laboratory information system. Independent risk factors for GDM were identified using univariate and multivariate logistic regression analyses. A GDM risk prediction model was constructed and evaluated with the Hosmer-Lemeshow goodness-of-fit test, goodness-of-fit calibration plot, receiver operating characteristic curve and area under the curve. RESULTS: Among traditional factors, age ≥30 years, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms (SNPs) (rs2779116, rs5215, rs11605924, rs7072268, rs7172432, rs10811661, rs2191349, rs10830963, rs174550, rs13266634 and rs11071657) were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. CONCLUSIONS: Both genetic and traditional factors contribute to the risk of GDM in women, operating through diverse mechanisms. Strengthening the risk prediction of SNPs for postpartum DM among women with GDM history is crucial for maternal and child health protection.

We aimed to evaluate a risk prediction model of gestational diabetes mellitus (GDM) based on traditional and genetic factors. A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to collect general data. Among traditional factors, age ≥30 years old, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. Both genetic and traditional factors increase the risk of GDM in women.

Effects of liraglutide on leptin promoter methylation in ovarian granulosa cells of patients with polycystic ovary syndrome and obesity.

OBJECTIVE: To explore the impacts of liraglutide on leptin promoter methylation in ovarian granulosa cells of patients with polycystic ovary syndrome and obesity. METHODS: A total of 30 patients with polycystic ovary syndrome and obesity were retrospectively analyzed. According to the method of random grouping, the patients were divided into an observation group and a control group. The control group received metformin, and the observation group received the subcutaneous injection of liraglutide. The therapeutic effects of patients in the two groups were compared. RESULTS: After therapy, the levels of glucose metabolism, lipid metabolism-related indicators, BMI, LEP, and VF of patients were less than those before therapy, and the levels in the observation group were less than the control group (p < 0.05). After therapy, the FSH, E2 and LH levels of patients in the two groups were less than those before therapy, and those in the observation one were less than the control group (p < 0.05). After therapy, the leptin promoter methylation in luteinized granulosa cells in the observation group was less than the control group (p < 0.05). The menstrual cycle establishment ratio, normal ovulation rate, and natural pregnancy ratio of the observation group was greater than the control group (p < 0.05). CONCLUSION: Liraglutide has a therapeutic effect on the patients with polycystic ovary syndrome and obesity by reducing the methylation of leptin promoter in luteinized granulosa cells and improving the natural pregnancy rate.

Family analysis and literature study of hereditary hypophosphatemic rickets with hypercalciuria.

BACKGROUND: Hereditary hypophosphatemia rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder characterised by reduced renal phosphate reabsorption leading to hypophosphataemia, rickets and bone pain. Here, we present a case of HHRH in a Chinese boy. CASE PRESENTATION: We report a 11-year-old female proband, who was admitted to our hospital with bilateral genuvarum deformity and short stature. Computed Tomography (CT) showed kidney stones, blood tests showed hypophosphatemia, For a clear diagnosis, we employed high-throughput sequencing technology to screen for variants. Our gene sequencing approach encompassed whole exome sequencing, detection of exon and intron junction regions, and examination of a 20 bp region of adjacent introns. Flanking sequences are defined as ±50 bp upstream and downstream of the 5' and 3' ends of the coding region.The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039), and the pathogenic variant sites were annotated using Annovar. Subsequently, the suspected pathogenic variants were classified according to ACMG's gene variation classification system. Simultaneously, unreported or clinically ambiguous pathogenic variants were predicted and annotated based on population databases. Any suspected pathogenic variants identified through this analysis were then validated using Sanger sequencing technology. At last, the proband and her affected sister carried pathogenic homozygous variant in the geneSLC34A3(exon 13, c.1402C > T; p.R468W). Their parents were both heterozygous carriers of the variant. Genetic testing revealed that the patient has anLRP5(exon 18, c.3917C > T; p.A1306V) variant of Uncertain significance, which is a rare homozygous variant. CONCLUSION: This case report aims to raise awareness of the presenting characteristics of HHRH. The paper describes a unique case involving variants in both theSLC34A3andLRP5genes, which are inherited in an autosomal recessive manner. This combination of gene variants has not been previously reported in the literature. It is uncertain whether the presence of these two mutated genes in the same individual will result in more severe clinical symptoms. This report shows that an accurate diagnosis is critical, and with early diagnosis and correct treatment, patients will have a better prognosis.

U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study.

Context: Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1. Objective: The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET). Methods: We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis. Results: A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. Conclusions: There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.

Elevated Thyroglobulin Antibody Level is Associated with Decreased Anti-Müllerian Hormone in Women of Reproductive Age.

Purpose: Women with Hashimoto's thyroiditis (HT) have an increased risk of ovarian insufficiency. However, whether thyroid antibodies affect the ovarian reserve remains controversial. The aim of this study was to explore the possible relationship between anti-Müllerian hormone (AMH) and thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels in women of reproductive age. Methods: A total of 483 women between 18 and 45 years old who had their TPOAb, TgAb, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and AMH levels measured on the same day were enrolled in this study. The levels of TSH, FT4, TPOAb, and TgAb, the prevalence of overt and subclinical hypothyroidism, and the positive rate of TPOAb and TgAb were compared between patients with low (below the 10th percentile), normal (10th to 90th percentile), and high (higher than the 90th percentile) AMH levels. Results: The median AMH level was 1.72 (0.33-4.27) ng/mL. A total of 9.9% of patients had low AMH levels. The TgAb levels and the prevalence of TgAb positivity were higher in the low AMH group (37.62 (13.10-232.68) IU/mL, 35.42%) than in the normal (12.46 (10.0-67.04) IU/mL, 19.59%) and high (13.61 (10.0-95.74) IU/mL, 23.4%) AMH groups (p=0.001, p=0.040, respectively). Serum AMH levels were inversely correlated with TgAb levels (r = -0.114, p=0.013). Conclusion: The AMH of women of reproductive age is affected by HT. Furthermore, women with the lowest AMH level had higher levels of TgAb and a positive rate of TgAb, and high TgAb levels may cause autoimmune damage to the ovaries.

Single-cell and spatial transcriptomics reveal POSTN+ cancer-associated fibroblasts correlated with immune suppression and tumour progression in non-small cell lung cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, the influence of CAF subpopulations on the progression of lung cancer is still unclear, which impedes the translational advances in targeting CAFs. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on tumour, paired tumour-adjacent, and normal samples from 16 non-small cell lung cancer (NSCLC) patients. CAF subpopulations were analyzed after integration with published NSCLC scRNA-seq data. SpaTial enhanced resolution omics-sequencing (Stereo-seq) was applied in tumour and tumour-adjacent samples from seven NSCLC patients to map the architecture of major cell populations in tumour microenvironment (TME). Immunohistochemistry (IHC) and multiplexed IHC (mIHC) were used to validate marker gene expression and the association of CAFs with immune infiltration in TME. RESULTS: A subcluster of myofibroblastic CAFs, POSTN+ CAFs, were significantly enriched in advanced tumours and presented gene expression signatures related to extracellular matrix remodeling, tumour invasion pathways and immune suppression. Stereo-seq and mIHC demonstrated that POSTN+ CAFs were in close localization with SPP1+ macrophages and were associated with the exhausted phenotype and lower infiltration of T cells. POSTN expression or the abundance of POSTN+ CAFs were associated with poor prognosis of NSCLC. CONCLUSIONS: Our study identified a myofibroblastic CAF subpopulation, POSTN+ CAFs, which might associate with SPP1+ macrophages to promote the formation of desmoplastic architecture and participate in immune suppression. Furthermore, we showed that POSTN+ CAFs associated with cancer progression and poor clinical outcomes and may provide new insights on the treatment of NSCLC.

Comparison of exenatide alone or combined with metformin versus metformin in the treatment of polycystic ovaries: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that exenatide and metformin are effective in the treatment of PCOS. In this meta-analysis, we aimed to compare the effectiveness and safety of exenatide alone or in combination with metformin versus metformin in patients suffering from PCOS. METHODS: RCTs of exenatide therapy were identified through a search of electronic databases in November 2022 and updated in October 2023. Eligible studies were identified independently by the reviewers. Outcomes were analysed with Revman 5.4. RESULTS: Nine RCTs among 214 studies on 1059 women with PCOS were included in the analysis, and among the nine RCTs, eight studies compared exenatide with metformin. Our meta-analysis demonstrated that exenatide was more effective than metformin in terms of pregnancy rate (RR 1.85 [95% CI 1.19,2.86] P = 0.006), sex hormone-binding globulin (SHBG) (MD 5 [95% CI 3.82,6.18] P < 0.001), and follicle-stimulating hormone (FSH) (MD 0.82 [95% 0.41,1.24] P < 0.001). The reductions in total testosterone (TT) (SMD -0.43 [95% CI -0.84, -0.03] P = 0.04) was more significant after treatment with exenatide than after treatment with metformin. In terms of safety, exenatide had a lower diarrhea rate (RR 0.11 [95% CI 0.01, 0.84]) than metformin. In the other three studies, exenatide plus metformin was compared with metformin. Exenatide combined with metformin was more effective in improving SHBG (MD 10.38[95%CI 6.7,14.06] P < 0.001), Matsuda index (MD 0.21[95%CI 0.05,0.37]) and reducing free androgen index (FAI) (MD -3.34 [-4.84, -1.83] P < 0.001), Weight (MD -2.32 [95%CI -3.89, -0.66]) and WC (MD-5.61[95%CI -8.4, -2.82] P < 0.001). The incidence of side effects between exenatide plus metformin and metformin was not statistically significant. CONCLUSIONS: Exenatide alone or in combination with metformin is more effective than metformin for women with PCOS. Considering the evidence on effectiveness and safety, exenatide alone or in combination with metformin may be a better treatment approach than metformin for women with PCOS. TRIAL REGISTRATION: INPLASY https://inplasy.com/inplasy-protocols/ ID: 10.37766/inplasy2022.11.0055.

Wolfram syndrome type 1: a case series.

BACKGROUND: Wolfram syndrome (WS) is a rare autosomal recessive multisystem neurodegenerative disease characterized by non-autoimmune insulin-dependent diabetes mellitus, optic atrophy, sensorineural deafness, and diabetes as the main features. Owing to clinical phenotypic heterogeneity, the misdiagnosis rate is high. However, early accurate diagnosis and comprehensive management are key to improving quality of life and prolonging life. RESULTS: Eleven patients from seven WS pedigrees with 10 mutation sites (c.1314_1317delCTTT, c.C529T, c.C529A, c.G2105A, c.C1885T, c.1859_1860del, c.G2020A, c.C529A, c.G2105A, and c.G1393C) in the WFS1 gene were included. We conducted further expert department analysis to clarify the diagnosis and analyze the correlation between genes and phenotypes. CONCLUSIONS: The genotypes of these patients were closely associated with their phenotypes. The clinical data of the patients were analyzed to provide a basis for the diagnosis and clinical management of the disease.

Circ_0004535/miR-1827/CASP8 network involved in type 2 diabetes mellitus with nonalcoholic fatty liver disease.

Diagnostic delay in type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) patients often leads to a serious public health problem. Understanding the pathophysiological mechanisms of disease will help develop more effective treatments. High-throughput sequencing was used to determine the expression levels of circRNAs, and mRNAs in health controls, T2DM patients, and T2DM with NAFLD patients. Differentially expressed genes (DEcircRs, DEmRs) in T2DM with NAFLD were identified by differential analysis. The miRNAs with targeted relationship with the DEcircRs and DEmRs were respectively predicted to construct a ceRNA regulatory network. In addition, enrichment analysis of DEmRs in the ceRNA network was performed. The expression of important DEcircRs was further validated by quantitative real-time PCR (qRT-PCR). The steatosis was detected in glucose treated LO2 cells by overexpressing circ_0004535, and CASP8. There were 586 DEmRs, and 10 DEcircRs in both T2DM and T2DM with NAFLD patients. Combined with predicted results and differential analysis, the ceRNA networks were constructed. The DEmRs in the ceRNA networks were mainly enriched in Toll-like receptor signaling pathway, and apoptosis. Importantly, dual luciferase experiments validated the targeted binding of hsa_circ_0004535 and hsa-miR-1827 or hsa-miR-1827 and CASP8. qRT-PCR experiments validated that hsa_circ_0004535, and CASP8 was downregulated and hsa-miR-1827 was upregulated expression in peripheral blood of T2DM with NAFLD patients. Abnormal cell morphology, and increased lipid droplet fusion were observed in the glucose treated LO2 cells, overexpression of circ_0004535 and CASP8 ameliorated these changes. Our work provides a deeper understanding of ceRNA mediated pathogenesis of T2DM with NAFLD and provides a novel strategy for treatment.

Associations between a polygenic risk score and the risk of gestational diabetes mellitus in a Chinese population: a case-control study.

Our objective was to construct a polygenic risk score (PRS) and assess its utility and effectiveness in predicting the risk of gestational diabetes mellitus (GDM) in a Chinese population. We performed a case-control study involving 638 patients with GDM and 1,062 healthy controls. Genotyping was conducted utilizing a genome-wide association study (GWAS), and a PRS was constructed. We identified 12 susceptibility loci that exhibited significant associations with the risk of GDM at a p-value threshold of ≤5.0 × 10-8, of which four loci were newly discovered. A higher PRS was associated with an increased risk of GDM (OR: 1.44; 95% CI: 1.03, 2.01 for the highest quartile compared to the lowest quartile). The PRS demonstrated a clear linear relationship with the fasting plasma glucose (FPG), 1-hour postprandial glucose (1hPG), and 2-hour postprandial glucose (2hPG) levels. The maximally adjusted ß coefficients and their corresponding 95% CIs were 0.181 (0.041, 0.320) for FPG, 0.225 (0.103, 0.346) for 1hPG, and 0.172 (0.036, 0.307) for 2hPG. Among the genetic variants examined, TCF7L2 rs7903146 displayed the strongest association with GDM risk (logOR = 0.18, p = 2.37 × 10-19), followed by ADAMTSL1 rs10963767 (logOR = 0.14, p = 3.58 × 10-15). The areas under the curve (AUCs) was significantly increased from 0.703 (0.678, 0.728) in the traditional risk factor model to 0.765 (0.741, 0.788) by including PRS. These findings indicate that pregnant women with a higher PRS could potentially derive considerable advantages from the implementation of a feasible PRS-based GDM screening program aimed at delivering precision prevention strategies within Chinese populations.

Pathogenicity of Congenital Adrenal Hyperplasia Induced by the p.P377L Mutation of CYP11B1.

CYP11B1 encodes an 11ß-hydroxylase that is involved in the catalysis of adrenal glucocorticoids and the production of cortisol. Mutations in CYP11B1 can result in congenital adrenal hyperplasia. We discovered a proband with a CYP11B1 gene mutation. Gene sequencing revealed a homozygous missense mutation of c.1130C > T in the 7th exon of the CYP11B1 gene that resulted in the change from Pro377 to leucine in the encoded protein. Based on the proband's clinical symptoms and the prognosis according to the database, this mutation may be harmful. However, the pathogenicity has not yet been reported. Thus, we created an expression vector for the mutation in vitro, transfected cells, observed the changes in gene expression, and determined its pathogenicity. To determine the pathogenicity of the CYP11B1 p.P377L mutation site through in vitro verification. The eukaryotic expression vector of the CYP11B1 mutation site was constructed in vitro, and the success of the construct was confirmed by sequencing. Fluorescence microscopy was used to determine the transfection effectiveness, GFP fluorescent tag labeling was used to detect changes in protein localization, and qRT‒PCR and Western blotting were used to detect CYP11B1 mRNA and protein expression. Sequencing revealed that the proband harbored a homozygous missense mutation of CYP11B1 (p.P377L). The expression of the protein decreased but the localization did not change when cells were transfected with the CYP11B1 mutation vector compared to the wild-type vector. The p.P377L mutation of CYP11B1 could affect protein expression and enzymatic activity and may be pathogenic.

The Role of Lignin in the Compartmentalization of Cadmium in Maize Roots Is Enhanced by Mycorrhiza.

In nature, arbuscular mycorrhizal fungi (AMF) play a crucial role in the root systems of plants. They can help enhance the resistance of host plants by improving the compartmentalization of toxic metal contaminants in the cell walls (CWs). However, the functions and responses of various CW subfractions to mycorrhizal colonization under Cd exposure remain unknown. Here we conducted a study to investigate how Cd is stored in the cell walls of maize roots colonized by Funneliformis mosseae. Our findings indicate that inoculating the roots with AMF significantly lowers the amount of Cd in the maize shoots (63.6 ± 6.54 mg kg-1 vs. 45.3 ± 2.19 mg kg-1, p < 0.05) by retaining more Cd in the mycorrhized roots (224.0 ± 17.13 mg kg-1 vs. 289.5 ± 8.75 mg kg-1, p < 0.01). This reduces the adverse effects of excessive Cd on the maize plant. Additional research on the subcellular distribution of Cd showed that AMF colonization significantly improves the compartmentalization of 88.2% of Cd in the cell walls of maize roots, compared to the 80.8% of Cd associated with cell walls in the non-mycorrhizal controls. We observed that the presence of AMF did not increase the amount of Cd in pectin, a primary binding site for cell walls; however, it significantly enhanced the content of lignin and the proportion of Cd in the total root cell walls. This finding is consistent with the increased activity of lignin-related enzymes, such as PAL, 4CL, and laccase, which were also positively impacted by mycorrhizal colonization. Fourier transform infrared spectroscopy (FTIR) results revealed that AMF increased the number and types of functional groups, including -OH/-NH and carboxylate, which chelate Cd in the lignin. Our research shows that AMF can improve the ability of maize plants to tolerate Cd by reducing the amount of Cd transferred from the roots to the shoots. This is achieved by increasing the amount of lignin in the cell walls, which binds with Cd and prevents it from moving through the plant. This is accomplished by activating enzymes related to lignin synthesis and increasing the exposure of Cd-binding functional groups of lignin. However, more direct evidence on the immobilization of Cd in the mycorrhiza-altered cell wall subfractions is needed.

Spatial transcriptome unveils a discontinuous inflammatory pattern in proficient mismatch repair colorectal adenocarcinoma.

The preexistence of immune cells in the tumor microenvironment substantiates the efficacy of immunotherapy in cancer patients. Although the complex intratumoral immune heterogeneity has been extensively studied in single cell resolution, hi-res spatial investigations are limited. In this study, we performed a spatial transcriptome analysis of 4 colorectal adenocarcinoma specimens and 2 paired distant normal specimens to identify the molecular pattern involved in a discontinuous inflammatory response in pathologically annotated cancer regions. Based on the location of spatially varied gene expression, we unmasked the spatially-varied immune ecosystem and identified the locoregional "warmed-up" immune response in predefined "cold" tumor with substantial infiltration of immune components. This "warmed-up" immune profile was found to be associated with the in-situ copy number variance and the tissue remodeling process. Further, "warmed-up" signature genes indicated improved overall survival in CRC patients obtained from TCGA database.

Insulin-like growth factor-1 levels are associated with interventricular septal thickening.

Background and objective: Insulin-like growth factor-1 (IGF-1) regulates cardiomyocyte survival, hypertrophy, and ageing. We aimed to investigate the potential correlation between IGF-1 and interventricular septal (IVS) thickening. Methods: Medical record data were obtained from patients hospitalized between May 1, 2012 and April 30, 2022. All patients underwent echocardiography and had laboratory data on plasma IGF-1. We analyzed the relationship between IGF-1 levels and IVS thickening based on logistic regression models. Results: Propensity score matching at 1:4 ratio was performed for 180 patients with IVS thickening and 1,964 patients without IVS thickening. Finally, 180 (case group) and 623 (control group) patients were enrolled. Of the total 803 patients, the mean age was 59 years, and 59.7% were male. In multivariate-adjusted models that adjusted for propensity scores, the risk of IVS thickening increased with increasing IGF-1 levels; specifically, the risk of IVS thickening increased per 1 ng/mL [odds ratio (OR) 1.003; 95% confidence interval (CI): 1.002-1.004; P < 0.001], per 5 ng/mL (OR, 1.016; 95% CI, 1.010-1.022; P < 0.001), and per 10 ng/mL(OR, 1.032; 95% CI, 1.019-1.045; P < 0.001) increase in IGF-1 levels. When the IGF-1 levels were expressed as a categorical variable, the increased levels of IGF-1 led to an increased risk of IVS thickening; specifically, the OR of IVS thickening for T3 >152.00 ng/mL was 2.020 (95% CI: 1.310-3.115, P < 0.01) compared with T1 <102.00 ng/mL. We performed restricted cubic splines, and it showed a linear association between IGF-1 levels and the risk of IVS thickening. In splines for the age and sex subgroups, different IGF-1 levels increased the risk of IVS thickening among different age groups in male patients: 18-44 years when IGF-1 value >164.00 ng/mL, 45-60 years when IGF-1 value > 140.34 ng/mL and ≥ 60 years when IGF-1 value >108.20 ng/mL. In female patients aged 45-60 years, the risk of IVS thickening increased when the IGF-1 levels were >207.45 ng/mL. However, IGF-1 was not significantly correlated with IVS thickening in female patients aged 18-45 and ≥60 years. Sensitivity analysis by excluding those with acromegaly did not change the relationship between IGF-1 and the risk of IVS thickening. Conclusion: The plasma IGF-1 levels were related to the risk of IVS thickening irrespective of blood pressure.

[Analysis of a patient with Kallmann syndrome and a 45,X/46,XY karyotype].

OBJECTIVE: To explore the etiology of a patient with Kallmann syndrome (congenital hypogonadism and anosmia) and a 45,X/46,XY karyotype. METHODS: Peripheral venous blood samples were collected from the proband and his parents and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the PROKR2 gene, namely c.533G>C (p.W178S) and c.308C>T (p.A103V), which were inherited from his father and mother, respectively. The two variants were respectively predicted to be likely pathogenic and variant of unknown significance, respectively. CONCLUSION: The reduced chromosomal mosaicism might have caused no particular clinical manifestations in this patient. For patients with features of Kallmann syndrome, genetic testing is conducive to early diagnosis and can provide a basis for genetic counseling and clinical treatment.

The non-linear relationship between triglyceride-glucose index and risk of chronic kidney disease in hypertensive patients with abnormal glucose metabolism: A cohort study.

Background: Triglyceride-glucose (TyG) index has been reported to be associated with cardiovascular disease (CVD). However, few studies have focused on TyG index and the risk of chronic kidney disease (CKD). Thus, this study aims to explore the relationship between TyG index and CKD. Methods: A total of 2,033 participants with hypertension between January 2012 and May 2019 were included in the longitudinal observational study. All patients are grouped according to the TyG index quartile. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 and/or positive proteinuria. Multivariate Cox proportional hazards models were used to investigate the relationship between TyG index and CKD. Results: During a median follow-up of 31 months, 302 participants developed CKD, with a mean age of 55.5 years and median TyG of 8.94. Compared with those in the lowest quartile of TyG index, participants in the highest quartile of TyG index exhibited 1.63-fold higher hazard ratio (95% CI: 1.14-2.33, P = 0.007) for presence of CKD. And restricted cubic spline analysis showed the relationship between TyG index and CKD is non-linear (P non-linearity = 0.021). The hazard ratio for CKD first fell and after rising until around 8.94 of TyG index and started to increase rapidly afterward (P for TyG < 0.001). Conclusion: Higher TyG index is associated with the increased risk for CKD. Early intervention of metabolic factors may prevent the occurrence of CKD, thereby reducing the incidence of CVD and premature death.

Genomic Survey of PEBP Gene Family in Rice: Identification, Phylogenetic Analysis, and Expression Profiles in Organs and under Abiotic Stresses.

Phosphatidylethanolamine-binding-protein (PEBP) domain-containing proteins play important roles in multiple developmental processes of plants; however, functions of few members in the PEBP gene family have been elucidated in rice and other crops. In this study, we found that twenty OsPEBPs genes identified in rice are not evenly distributed on the chromosomes. Four colinear pairs are identified, suggesting the duplication of OsPEBPs during evolution. The OsPEBPs are classified into six subgroups by phylogenetic analysis. The structure of all the OsPEBP genes and encoded proteins are similar. The 262 PEBP domain-containing proteins from crops are divided into six groups. The number of colinear pairs varies between rice and other crops. More than thirty cis-acting elements in the promoter region of OsPEBPs are discovered. Expression profiles of OsPEBP genes are differential. Most of the OsPEBPs expression can be regulated by NaCl, ABA, JA, and light, indicating that OsPEBPs may be involved in the control of the response to the environmental signals. These results lay sound foundation to further explore their functions in development of rice and crops.

Pharmacokinetics of neomycin sulfate after intravenous and oral administrations in swine.

The aminoglycoside antibiotic neomycin, which is used to treat external or internal bacterial infections, is primarily administered in veterinary medicine as a sulfate salt. However, no information is available on the pharmacokinetic characteristics and absolute availability of neomycin sulfate after intravenous (i.v.) and oral (p.o.) administrations in swine. Here, these parameters were studied in swine after i.v. and p.o. doses of single 15 mg/kg body weight doses. The blood samples were assessed using ultra-high-performance liquid chromatography-tandem mass/mass spectrometry (UPLC-MS/MS) and pharmacokinetic parameters were analyzed using a non-compartmental model. In swine, after the p.o. administration, the elimination half-life, mean residue time from t0 to the last collection point, mean maximum concentration, mean time to reach maximum concentration and area under concentration-time curve from t0 to the last collection point values were 12.43 ± 7.63 h, 10.25 ± 4.32 h, 0.11 ± 0.07 µg/ml, 1.92 ± 0.97 h and 1.23 ± 0.78 µg·h/ml, respectively, whereas after the i.v. administration, the values were 5.87 ± 1.12 h, 6.07 ± 0.49 h, 15.80 ± 1.32 µg/ml, 0.30 ± 0.38 h and 76.14 ± 3.52 µg·h/ml, respectively. The absolute bioavailability of neomycin sulfate B was 4.84%±0.03.

Non-Classical 21-Hydroxylase Deficiency: Analysis of a Mutant Gene in a Uyghur Family and Literature Review.

OBJECTIVE: The gene mutation and clinical characteristics of a patient with non-classical 21-hydroxylase deficiency and his family were analyzed. METHODS: A patient was diagnosed with non-classical 21-hydroxylase deficiency in the Department of Endocrinology of People's Hospital of Xinjiang Uygur Autonomous Region in December 2016. The clinical data and related gene-sequencing results were analyzed. The detected mutations were verified in nine members of the family. RESULTS: Gene-sequencing results revealed that the proband and the other three members of the family (proband, proband's mother's younger brother and the proband's mother's younger brother's younger daughter, and proband's second elder sister) shared the following mutations: Ile173Asn, Ile237Asn, Val238Glu, Met240Lys, Val282Leu, Leu308Phefs*6, Gln319Ter, Arg357Trp, and Arg484Profs. The Val282Leu mutation was heterozygous in the proband's mother's younger brother's younger daughter, but homozygous in the other three individuals. The father of the proband, the elder brother of the father of the proband, the third younger brother of the father of the proband, and the elder sister of the proband all carried only the Val282Leu mutation. CONCLUSION: Val282Leu is the gene responsible for non-classical 21-hydroxylase deficiency. Screening for this gene in the offspring of patients with non-classical 21-hydroxylase deficiency may help to identify cases early.

Impact of Abdominal Obesity on Thyroid Auto-Antibody Positivity: Abdominal Obesity Can Enhance the Risk of Thyroid Autoimmunity in Men.

BACKGROUND: The interrelation between obesity and autoimmune thyroid diseases is complex and has not been confirmed. The aim of the present study was to observe the relationship between thyroid autoimmunity and obesity, especially abdominal obesity, in a large population. METHODS: A total of 2253 residents who had lived in Xinjiang for more than 3 years were enrolled. Serum thyroid hormone concentration, thyroid autoantibodies, lipid parameters, Weight, height, and waist and hip circumference were measured. RESULTS: The prevalence of thyroid peroxidase antibody (TPOAb) and/or thyroglobulin antibody (TgAb) positive was 32.1% (21.2% in men and 37% in women, P < 0.01). Compared with women, men had significantly higher TG levels, waist circumference, and hip circumference levels (P < 0.01), while women showed higher TSH, TPOAb, and TgAb levels (P < 0.01). The prevalence of overweight and obesity was 71.1% in men and 63.5% in women. Men had a higher prevalence of abdominal obesity than women (56.6% in men and 47.6% in women, P < 0.01). TPOAb correlates positively with waist circumference (r = 0.100, P < 0.05) in men. Binary logistic analysis showed that TPOAb positivity had increased risks of abdominal obesity in men, and the OR was 1.1044 (95% CI 1.035, 1.151, P < 0.05). CONCLUSION: Our results indicate that men had higher lipid levels, thicker waist circumference, and higher prevalence of overweight, obesity, and abdominal obesity. Abdominal obesity is a risk factor for TPOAb positivity in men, suggesting that abdominal obesity can enhance the risk of thyroid autoimmunity in men.