Inflammation, nutrition, and biological aging: The prognostic role of Naples prognostic score in nonalcoholic fatty liver disease outcomes.

AIM: This study aimed to evaluate the prognostic value of the Naples Prognostic Score (NPS) for predicting mortality in patients with nonalcoholic fatty liver disease (NAFLD) and compare its performance with established non-invasive fibrosis scores, including the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). METHODS: Data from 10,035 NAFLD patients identified within the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Cox regression models assessed the association between NPS and all-cause mortality, while time-dependent ROC analysis compared its predictive accuracy with FIB-4 and NFS. Mediation analysis explored the role of phenotypic age acceleration (PhenoAgeAccel). RESULTS: NPS was significantly associated with all-cause mortality, with each point increase corresponding to a 26 % increased risk (HR = 1.26, 95 % CI: 1.19-1.34). NPS demonstrated comparable predictive performance to FIB-4 and NFS, with further improvement when combined with either score (HRs of 2.03 and 2.11 for NPS + FIB-4 and NPS + NFS, respectively). PhenoAgeAccel mediated 31.5 % of the effect of NPS on mortality. CONCLUSIONS: This study found that NPS has the potential to be an independent, cost-effective, and reliable novel prognostic indicator for NAFLD that may complement existing tools and help improve risk stratification and management strategies for NAFLD, thereby preventing adverse outcomes.

Non-classical 11ß-hydroxylase deficiency caused by a novel heterozygous mutation: a case report and review of the literature.

PURPOSE: 11ß-hydroxylase deficiency (11ß-OHD) constitutes a rare form of congenital adrenal hyperplasia (CAH), typically accounting for ~5-8% of CAH cases. Non-classical 11ß-OHD is reported even more rarely and frequently results in misdiagnosis or underdiagnosis due to its mild clinical symptoms. METHODS: A clinical, biochemical, radiological, and genetic study was conducted on a 9-year-old girl presenting with mild breast development, axillary hair growth, and advanced bone age. Additionally, a comprehensive review and synthesis of the literature concerning 11ß-OHD were conducted. RESULTS: The patient presented with breast enlargement, axillary hair development, and accelerated growth over the past year. Laboratory tests revealed levels of cortisol, luteinizing hormone, testosterone, and progesterone that were below normal. A gonadotropin-releasing hormone (GnRH) stimulation test suggested the possibility of central precocious puberty. Radiologic examination revealed a 2-year advance in bone age, while bilateral adrenal ultrasonography showed no abnormalities. Her mother exhibited hirsutism, while her father's physical examination revealed no abnormalities. Whole-exon genetic testing of the child and her parents indicated a heterozygous mutation of c.905_907delinsTT in exon 5 of the 11ß-hydroxylase gene (CYP11B1) in the child and her mother. This mutation resulted in a substitution of aspartic acid with valine at amino acid position 302 of the coding protein. This frameshift resulted in a sequence of 23 amino acids, culminating in a premature stop codon (p.Asp302ValfsTer23). A review of the previous literature revealed that the majority of heterozygous mutations in 11ß-OHD were missense mutations, occurring primarily in exons 2, 6, 7, and 8. The most common mutation among 11ß-OHD patients was the change of Arg-448 to His (R448H) in CYP11B1. Furthermore, bioinformatics analyses revealed that heterozygous mutation of c.905_907delinsTT had deleterious effects on the function of CYP11B1 and affected the stability of the protein, presumably leading to a partial impairment of enzyme activity. The results of the in vitro functional study demonstrated that the missense mutant (p.Asp302ValfsTer23) exhibited partial enzymatic activity. CONCLUSIONS: We report a novel heterozygous mutation of CYP11B1 (c.905_907delinsTT), enriching the spectrum of genetic variants of CYP11B1. This finding provides a valuable case reference for early diagnosis of non-classical patients with 11ß-OHD.

Serum Uric Acid to Creatinine Ratio and Risk of Metabolic Syndrome in Patients with Overweight/Obesity.

Purpose: Metabolic syndrome (MetS) is a rising global concern with an increasing prevalence. This study aimed to evaluate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and MetS in adults with overweight/obesity in China. Patients and Methods: We conducted a cross-sectional study comprising 4699 participants with overweight/obesity who underwent physical examinations. Their serum levels of various components, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), fasting plasma glucose (FPG), creatinine (Cr), and uric acid (UA) were measured. Renal function-normalized SUA was calculated using SUA/Cr. Logistic regression analysis was employed to investigate the association between SUA/Cr and MetS in adults with overweight/obesity. Results: SUA/Cr levels were lower in non-MetS participants (OR: 2.159, 95% CI: 1.82 to 2.56; p < 0.001), and tended to rise with the increasing number of MetS components. Additionally, elevated SUA/Cr levels were associated with a higher risk of hypertension, hyperglycemia, and dyslipidemia. Conclusion: SUA/Cr levels were significantly associated with MetS and its components in Chinese adults with overweight/obesity.

Identifying Metabolic Syndrome Easily and Cost Effectively Using Non-Invasive Methods with Machine Learning Models.

Purpose: The objective of this study was to employ machine learning (ML) models utilizing non-invasive factors to achieve early and low-cost identification of MetS in a large physical examination population. Patients and Methods: The study enrolled 9171 participants who underwent physical examinations at Northern Jiangsu People's Hospital in 2009 and 2019, to determine MetS based on criteria established by the Chinese Diabetes Society. Non-invasive characteristics such as gender, age, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected and used as input variables to train and evaluate ML models for MetS identification. Several ML models were used for MetS identification, including logistic regression (LR), k-nearest neighbors algorithm (k-NN), naive bayesian (NB), decision tree (DT), random forest (RF), artificial neural network (ANN), and support vector machine (SVM). Results: Our ML models all showed good performance in the 10-fold cross-validation except for the SVM model. In the external validation, the NB model exhibited the best performance with an AUC of 0.976, accuracy of 0.923, sensitivity of 98.32%, and specificity of 91.32%. Conclusion: This study proposed a new non-invasive method for early and low-cost identification of MetS by using ML models. This approach has the potential to serve as a highly sensitive, convenient, and cost-effective tool for large-scale MetS screening.

MicroRNA-376b is involved in the pathogenesis of thyroid-associated ophthalmopathy by regulating HAS2.

PURPOSE: The aim of this study was to investigate the microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMC) of thyroid-associated ophthalmopathy (TAO) patients and to explore the molecular mechanisms of MicroRNA-376b (miR-376b) in the pathogenesis of TAO. METHODS: PBMCs from TAO patients and healthy controls were analyzed by miRNA microarray to screen for the significantly differentially expressed miRNAs. The miR-376b expression in PBMCs were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The downstream target of miR-376b was screened by online bioinformatics, and detected by qRT-PCR and Western blotting. RESULTS: Compared with normal controls, 26 miRNAs were significantly different in PBMCs of TAO patients (14 miRNAs were down-regulated and 12 miRNAs were up-regulated). Among them, miR-376b expression was significantly decreased in PBMCs from TAO patients compared to healthy controls. Spearman correlation analysis revealed that miR-376b expression in PBMCs was significantly negatively correlated with free triiodothyronine (FT3), and positively correlated with thyroid-stimulating hormone (TSH). MiR-376b expression was obviously reduced in 6T-CEM cells after triiodothyronine (T3) stimulation compared to controls. MiR-376b mimics significantly decreased hyaluronan synthase 2 (HAS2) protein expression and the mRNA expression of intercellular cell adhesion molecule-1 (ICAM1) and tumor necrosis factor-α (TNF-α) in 6T-CEM cells, whereas miR-376b inhibitors markedly elevated HAS2 protein expression and gene expression of ICAM1 and TNF-α. CONCLUSIONS: MiR-376b expression in PBMCs was significantly decreased in PBMCs from TAO patients compared with the healthy controls. MiR-376b, regulated by T3, could modulate the expression of HAS2 and inflammatory factors. We speculate that miR-376b may be involved in the pathogenesis of TAO patients by regulating the expression of HAS2 and inflammatory factors.

Effects of Hyperthyroidism on Venous Thromboembolism: A Mendelian Randomization Study.

Objective: Observational studies show the correlation between thyroid dysfunction and risk of venous thromboembolism. However, the causal effects remain uncertain. Our study was conducted to evaluate whether thyroid function and dysfunction were causally linked to the risk of venous thromboembolism. Methods: Publicly available summary data of thyrotropin (TSH) and free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained from the ThyroidOmics Consortium and the UK Biobank. With single nucleotide polymorphisms (SNPs) as instrumental variables, the casual effects of genetically predicted TSH and FT4 and hypo- and hyperthyroidism on venous thromboembolism outcome were estimated through Mendelian randomization analysis methods (inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode). Cochran's Q test was performed to evaluate the heterogeneity and horizontal pleiotropy. Results: Our study selected 15 FT4-, 36 TSH-, 3 hyperthyroidism-, and 79 hypothyroidism-associated SNPs as instrumental variables. The IVW analysis results showed that the odds ratio of venous thromboembolism for hyperthyroidism was 1.124 (95% confidence interval: 1.019-1.240; p = 0.019), demonstrating the casual effect of hyperthyroidism not FT4, TSH, and hypothyroidism on venous thromboembolism. No heterogeneity or horizontal pleiotropy was observed according to Cochran's Q test. Conclusion: Our Mendelian randomization analysis supports the causal effect of hypothyroidism on risk of venous thromboembolism. There is no evidence that genetically predicted TSH, FT4, and hypothyroidism have casual effects on venous thromboembolism. Future studies should be conducted to elucidate the underlying pathophysiological mechanisms.

Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai.

Objective: To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods: A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result: Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8-15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8-15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50-64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions: Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Prospective Memory and Regional Functional Connectivity in Subcortical Ischemic Vascular Disease.

Objectives: Patients with subcortical ischemic vascular disease (SIVD) often have prominent frontal dysfunction. However, it remains unclear how SIVD affects prospective memory (PM), which strongly relies on the frontoparietal network. The present study aimed to investigate PM performance in patients with early stage SIVD as compared to those with Alzheimer's disease (AD) and to older adults with normal cognition, and to explore the neural correlates of PM deficits. Method: Patients with very-mild to mild dementia due to SIVD or AD and normal controls (NC) aged above 60 years were recruited. Seventy-three participants (20 SIVD, 22 AD, and 31 NC) underwent structural magnetic resonance imaging (MRI), cognitive screening tests, and a computerized PM test. Sixty-five of these participants (19 SIVD, 20 AD, and 26 NC) also received resting-state functional MRI. Results: The group with SIVD had significantly fewer PM hits than the control group on both time-based and non-focal event-based PM tasks. Among patients in the very early stage, only those with SIVD but not AD performed significantly worse than the controls. Correlational analyses showed that non-focal event-based PM in SIVD was positively correlated with regional homogeneity in bilateral superior and middle frontal gyri, while time-based PM was not significantly associated with regional homogeneity in any of the regions of interest within the dorsal frontoparietal regions. Conclusions: The findings of this study highlight the vulnerability of non-focal event-based PM to the disruption of regional functional connectivity in bilateral superior and middle frontal gyri in patients with SIVD.

Prevalence of vitamin D deficiency in the pregnant women: an observational study in Shanghai, China.

BACKGROUND: Maternal vitamin D deficiency has been a worldwide concern in recent years. However the epidemiological data of vitamin D deficiency among large group of Chinese pregnant women is limited. This study is to evaluate the prevalence of vitamin D deficiency among pregnant women in Shanghai, China and to analyze the association of vitamin D status with some pregnancy outcomes (gestational diabetes and low birth weight). METHODS: A total of 34,417 pregnant women in Shanghai were included in this study from January 2014 to December 2017, and the serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 16th week of gestation by electrochemiluminescence assay. Seventy five grams of glucose was used to conduct oral glucose tolerance test during 24-28th week of gestational in all enrolled persons and the birth weight of newborns was recorded. RESULTS: The median serum 25(OH) D concentration in the pregnant women during 4 years was 42.87 nmol/L (32.88-51.90 nmol/L). 9.9% of the population were severe vitamin D deficient [25(OH)D < 25 nmol/L], 60.1% were deficient [25 nmol/L ≤ 25(OH)D < 50 nmol/L], 28.4% were insufficient [50 nmol/L ≤ 25(OH)D < 75 nmol/L] and only 1.6% of the enrolled population reached the level of adequate [25(OH)D ≥ 75 nmol/L]. Serum 25(OH) D concentrations showed significant difference among seasons with the highest level in winter and the lowest level in summer. Women with advanced maternal age were more likely to have better vitamin D status compared with younger women. The 25(OH) D levels were significantly different among 2014-2017. The year of 2017 had the highest 25(OH) D level with the median serum concentration reaching 47.80 nmol/L (41.00-55.00 nmol/L), while the lowest appeared in 2016 which has median 25(OH) D concentration at 38.87 nmol/L (28.76-49.97 nmol/L). No relations were found between the 25(OH) D status and the rate of gestational diabetes or low birth weight of newborns. CONCLUSION: Pregnant women in Shanghai were generally deficient in vitamin D status and the level of vitamin D was related to season and age. No evidence showed vitamin D deficiency in pregnant women contributes to the rate of gestational diabetes or low birth weight of newborns in this study. These results suggest that most of the pregnant women may need vitamin D supplementation to achieve adequate vitamin D level.

Fine mapping of thyroglobulin gene identifies two independent risk loci for Graves' disease in Chinese Han population.

BACKGROUND: This study aimed to determine independent risk loci of Graves' disease (GD) in the thyroglobulin (TG) region. METHODS: In this two-staged association study, a total of 9,757 patients with GD and 10,626 sex-matched controls were recruited from Chinese Han population. Illumina Human660-Quad BeadChips in the discovery stage and TaqMan SNP Genotyping Assays in the replication stage were used for genotyping. Trend test and logistic regression analysis were performed in this association study. RESULTS: In the discovery stage, rs2294025 and rs7005834 were the most highly associated susceptibility loci with GD in TG. In the replication phase, 7 SNPs, including rs2294025 and rs7005834, were selected for fine-mapping. Finally, we confirmed that rs2294025 and rs7005834 were the independent risk loci of GD in the combined populations. At the same time, there was no significant difference between the risk allele frequencies of rs2294025 and rs7005834 in different clinical phenotypes of GD. CONCLUSIONS: The fine mapping study of thyroglobulin identified two independent SNPs (rs2294025 and rs7005834) for GD susceptibility. However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody. These results provide a deeper understanding of the association mechanism of thyroglobulin and GD risk.

Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study.

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

Nomograms Predicting Self-Regulated Learning Levels in Chinese Undergraduate Medical Students.

PURPOSE: The purpose of this study was to construct a multi-center cross-sectional study to predict self-regulated learning (SRL) levels of Chinese medical undergraduates. METHODS: We selected medical undergraduates by random sampling from five universities in mainland China. The classical regression methods (logistic regression and Lasso regression) and machine learning model were combined to identify the most significant predictors of SRL levels. Nomograms were built based on multivariable models. The accuracy, discrimination, and generalization of our nomograms were evaluated by the receiver operating characteristic curves (ROC) and the calibration curves and a high quality external validation. RESULTS: There were 2052 medical undergraduates from five universities in mainland China initially. The nomograms constructed based on the non-overfitting multivariable models were verified by internal validation (C-index: learning motivation: 0.736; learning strategy: 0.744) and external validation (C-index: learning motivation: 0.986; learning strategy: 1.000), showing decent prediction accuracy, discrimination, and generalization. CONCLUSION: Comprehensive nomograms constructed in this study were useful and convenient tools to evaluate the SRL levels of undergraduate medical students in China.

Postnatal deletion of ß-catenin in osterix-expressing cells is necessary for bone growth and intermittent PTH-induced bone gain.

wnt/ß-catenin signaling has been shown to influence bone homeostasis and is important for parathyroid hormone (PTH)-induced bone gain. To further understand the role of ß-catenin in the early stages of osteoblastic lineage cells for postnatal bone homeostasis and the anabolic actions of PTH on bone, we examined mice with postnatal disruption of ß-catenin in osterix-expressing cells (ß-catenin KO mice) by mating floxed ß-catenin mice with transgenic mice expressing cre under the control of the osterix promoter suppressible by doxycycline. After withdrawal of doxycycline, ß-catenin KO mice developed progressive bone loss, ectopic cartilage formation, accumulation of mesenchymal stromal cells, and bone marrow adiposity. The ß-catenin-defective osteoblasts sorted by flow cytometry from ß-catenin KO mice exhibited decreased EdU incorporation, increased annexin V activity, and profound alterations in gene expression including wnt target genes, osteoclast regulators, and osteoblast markers. A dramatic increase in osteoclasts was observed in both neonatal and postnatal ß-catenin KO mice. Intermittent administration of PTH for 4 weeks significantly increased bone mass in control mice; however, this anabolic effect of PTH was substantially blunted in ß-catenin KO mice. Our data indicate that ß-catenin in osterix-expressing cells is required for postnatal osteoblast differentiation, osteoblast proliferation, and bone resorption, and is essential for the anabolic actions of PTH in bone.

Injury to the endothelial surface layer induces glomerular hyperfiltration rats with early-stage diabetes.

Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes.

Association of LRP5 gene polymorphism with type 2 diabetes mellitus and osteoporosis in postmenopausal women.

This study was to explore the association of low-density lipoprotein receptor related protein 5 (LRP5) gene polymorphism with bone mineral density (BMD), bone turnover markers and glycometabolism in postmenopausal women with type 2 diabetes mellitus (T2DM) and/or osteoporosis (OP) in Shanghai. 354 unrelated Han Chinese post-menopausal women were recruited from Shanghai and divided into 4 groups: OP group (n=90), T2DM group (n=96), T2DM + OP group (n=90) and control group (n=78). The LRP5 genotypes were determined by DNA sequencing. The BMD was measured by dual-energy X-ray absorptiometry. The bone transformation indicators and glycometabolism index (HbA1c and Fasting insulin) were also detected. The association of LRP5 polymorphism with BMD, bone turnover markers and glycometabolism was evaluated. Result showed that, In OP group, the BMD of L2-4 was higher in patients with rs3736228 CC genotype than those with CT/TT genotypes (P<0.05). After adjustment for age, body mass index (BMI) and years of menopause, A1330V polymorphism was still associated with BMD of L2-4 (P<0.01). In the control group, HbA1c was significantly higher in patients with A1330V CC genotype than those with CT/TT genotypes (P<0.05), but no significant difference was found after adjustment for BMI, age and years of menopause (P>0.05). Thus, LRP5 gene is an impressionable gene in postmenopausal women with OP in Shanghai. T2DM patients have a high BMD when compared with controls, which may be related to BMI and FINS. LRP5 genotype is not an impressionable gene in postmenopausal women with T2DM in Shanghai.

The impact of gender, age and tissues in vitro on estimating postmortem interval by FTIR spectroscopy.

To investigate the influence of such individual factors as gender, age and tissues in vitro to the postmortem interval (PMI) by the Fourier transform infrared (FTIR) spectrometer in animal experiments. SD rats were classified into male and female groups, different age groups (21-day, 42-day and 63-day group), and tissues in vitro and in vivo groups. The rats were sacrificed by cervical dislocation, whose bodies were kept in a controlled environmental chamber set at (20+/-2) degrees C and 50% humidity. The liver, kidney, spleen, myocardium, brain, lung and skeletal muscle tissues were collected for measurement from time zero to 48 h postmortem. With the change of PMI, no obvious changes were found in the main FTIR absorbance peaks and their ratios at different time points. All the experimental groups showed no significant changes when compared with the controls. The gender, age and tissues in vitro were not found to be contributing factors in the estimation of PMI via FTIR spectroscopy.

Comparison of parathyroid hormone (1-34) and elcatonin in postmenopausal women with osteoporosis: an 18-month randomized, multicenter controlled trial in China.

BACKGROUND: Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. METHODS: A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. RESULTS: rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group. CONCLUSIONS: rhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.

[Association of single nucleotide polymorphisms in the promoter region of the TLR9 gene with childhood atopic asthma].

OBJECTIVE: To investigate the distribution characteristics of the single nucleotide polymorphisms (SNPs) in the promoter region of the toll-like receptor 9 gene (TLR9) in Chinese Han children from Zhejiang province, and their associations with asthma susceptibility and phenotypes. METHODS: A case-control study was conducted. A total of 312 asthmatic children aged between 1.9 and 11.6 and 339 age matched healthy controls were enrolled in this study from April 2007 to November 2008. The -1486 C/T in rs187084 and -1237 C/T in rs5743836 loci of the TLR9 gene were genotyped by direct DNA sequencing of the PCR products. Serum levels of IFN gamma, IL-12 and IL-4 were detected by enzyme linked immunosorbent assay.Serum levels of total IgE were detected by chemiluminescence, and serum levels of antigen specific IgE antibodies were detected by fluoroenzymeimmunoassay. RESULTS: (1) The -1486 C/T polymorphism was identified in both groups. The genotype frequencies of TT, TC and CC at -1486 C/T were 41.0%, 44.3%, 14.7% in the healthy controls, and 38.8%, 48.4%, 12.8% in the asthmatic children. The -1237 C/T polymorphism was not detected in the population. (2) There were no statistically significant differences in the allele and genotype frequencies at the -1486 C/T locus between the two groups (P;>0.05). (3) Serum levels of IFN gamma and IL-4 differed significantly among the three genotypes at the -1486 C/T locus in asthmatic children (P<0.01). The CC genotype had the lowest levels of serum IFN gamma and the highest levels of serum IL-4 among the three genotypes. There were no significant differences in these cytokines among the healthy controls (P>0.05). No statistical differences of serum IL-12 were found among the three genotypes in the two groups (P>0.05). (4) There were no significant differences of total IgE (log-transformed) among the three genotypes in the asthmatic children (P>0.05). CONCLUSION: The -1237 C/T polymorphism of TLR9 gene was not detected in Chinese Han children in this study. The -1486 C/T polymorphism was associated with the levels of serum IFN gamma and IL-4 in children with asthma. However, there were no correlations between the -1486C/T polymorphism and serum IL-12 levels, total IgE levels or asthmatic susceptibility.

[A randomized, multicenter, active-controlled trial to compare the efficacy of recombinant human parathyroid hormone (1-34) with that of elcatonin in postmenopausal women with osteoporosis in China].

OBJECTIVE: To compare the clinical efficacy and safety between recombinant human parathyroid hormone (rhPTH) (1-34) and elcatonin in the treatment of postmenopausal women with osteoporosis in China. METHODS: This 6 month, multicenter, randomized and controlled study enrolled 205 postmenopausal women with osteoporosis. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily or elcatonin 20 U weekly. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD) and biochemical markers of bone turnover were measured. In the meantime adverse events were recorded. RESULTS: The results showed that both rhPTH (1-34) and elcatonin increased L1-4 BMD significantly at the endpoint of the study, but femoral neck BMD did not change significantly. From baseline to endpoint, BMD of L1-4 and femoral neck in the rhPTH (1-34) group increased by 5.51% (P<0.01) and 0.65% (P>0.05), but BMD of L1-4 and femoral neck in elcatonin group increased by 1.55% (P<0.05) and 0.11% (P>0.05). Moreover, the rhPTH (1-34) group had better improvement in L1-4 BMD than the elcatonin group at 3, 6 months, but there was no difference of BMD in these two groups with regard to femoral neck. There were greater mean increases of the bone markers in the rhPTH (1-34) group than those in the elcatonin group at 3, 6 months [serum bone-specific alkaline phosphatase (BSAP) 36.79% vs 0.31%; 92.42% vs -0.17%; the ratio of urine N-telopeptide of type I collagen and creatinine (NTX/Cr) 48.91% vs -5.32%; 68.82% vs -10.86%]. Both kinds of treatment were well tolerated and there were no differences between the two groups in the rates of adverse events and serious adverse events. CONCLUSION: It is concluded that rhPTH (1-34) has more positive effects on bone formation than elcatonin as shown by the greater increments of L1-4 BMD and bone formation markers and the less occurrence of adverse events as well as no significant change in hepatic, renal or hemopoietic function.

[The pathological effects of snoring on pregnant women].

OBJECTIVE: To discuss the pathological effect of snoring on pregnant women in Wenzhou area. METHODS: The study was performed between January 2006 and February 2008, 601 women with pregnancies being in clinic or the ward were surveyed about snoring occur, measuring physiological and biochemical parameters in the 13th, 28th week of pregnancy and before delivery, recording the complication and pregnancy outcome. According to their pregnancy and snoring occur, they were divided into the first, the second and the third trimester snoring group and non-snoring group. RESULT: Compared with the non-snoring group, The BMI, abdominal perimeter, the neck circumference and systolic blood pressure in snoring group of every trimester increased significantly (P<0.05). There were no significant differences about the hip circumference of snoring group in the first trimester (P>0.05), but they increased significantly in the second and the third trimester (P<0.05). There were no significant differences about the diastolic blood pressure of snoring group in the first and the second trimester (P>0.05), but they increased significantly in the third trimester (P<0.05). There were no significant differences about the snoring group's BMI, abdominal perimeter, the neck circumference, the hip circumference and blood pressure between the groups of every trimester (P>0.05). Compared with the non-snoring group, the incidence of snoring group's gestational hypertension, premature birth and abdominal delivery increased significantly every trimester of pregnancy (P<0.05). There were no significant differences Between the snoring groups of every trimester (P>0.05). CONCLUSION: The snore makes pregnant women physiological characteristics changed, the incidence of gestational hypertension, premature delivery and abdominal delivery increased. So we should pay more attentions to them in their perinatal stage.