Association between short-term exposure to ambient air pollution and upper respiratory tract infection in Kunshan.

The health effects of air pollution have become a major public health problem. Studies on the relationship between short-term exposure to air pollutants and upper respiratory tract infection (URTI) related clinic visits and expenditures were scarce. From January 1, 2019, to December 31, 2021, we included all the URTI cases that turned to 11 public hospitals in Kunshan, and summarized individual medical cost. Daily meteorological factors and 24-h mean concentrations of four common air pollutants, including particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and 10 µm (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2), were consecutively recorded. Generalized additive regression model was adopted to quantify the associations between each air pollutant and the daily clinic visits of URTI cases. We further calculated attributable number (AN) and attributable fraction, and performed sensitivity analysis by gender, age, and season. A total of 934,180 cases were retrieved during the study period. PM2.5, PM10, SO2, and NO2 showed significant associations with hospital visits and expenditures due to URTI. Relative risks for them were 1.065 (95% confidence interval [CI] 1.055, 1.076), 1.045 (95% CI 1.037, 1.052), 1.098 (95% CI 1.038, 1.163), and 1.098 (95% CI 1.085, 1.111) on lag 0-5 days, respectively. Thirty-one thousand four hundred fifty-five (95% CI 27,457, 35,436) cases could be ascribed to increased NO2 and accounted for 3.37% (95% CI 2.94%, 3.79%) of all clinic visits. Sensitivity analyses indicated that the effects of air pollution were generally consistent for male and female. PM2.5, PM10, and NO2 had stronger associations among people aged ≤ 18 years, followed by those aged 19-64 years and ≥ 65 years. The association strengths of air pollution varied seasonally. Short-term exposure to ambient air pollutants had significant associations with clinic visits and expenditures owing to URTI. Children and adolescents appeared to be more susceptible to adverse health effects of air pollution. NO2 may be a priority when formulating pollution control measures.

Lipid Droplet Targeting Type I Photosensitizer for Ferroptosis via Lipid Peroxidation Accumulation.

As an iron-dependent lipid peroxidation (LPO) mediated cell death pathway, ferroptosis offers promises for anti-tumor treatment. Photodynamic therapy (PDT) is an ideal way to generate reactive oxygen species (ROS) for LPO. However, the conventional PDT normally functions on subcellular organelles, such as endoplasmic reticulum, mitochondria, and lysosome, causing rapid cell death before triggering ferroptosis. Herein, the first lipid droplet (Ld)-targeting type I photosensitizer (PS) with enhanced superoxide anion (O2 -· ) production, termed MNBS, is reported. The newly designed PS selectively localizes at Ld in cells, and causes cellular LPO accumulation by generating sufficient O2 -· upon irradiation, and subsequently induces ferroptosis mediated chronical PDT, achieving high-efficient anti-tumor PDT in hypoxia and normoxia. Theoretical calculations and comprehensive characterizations indicate that the Ld targeting property and enhanced O2 -· generation of MNBS originate from the elevated H-aggregation tendency owing to dispersed molecular electrostatic distribution. Further in vivo studies using MNBS-encapsulated liposomes demonstrate the excellent anti-cancer efficacy as well as anti-metastatic activity. This study offers a paradigm of H-aggregation reinforced type I PS to achieve ferroptosis-mediated PDT.

Association of follicle-stimulating hormone with lipid profiles in older women: a cross-sectional SPECT-China study.

AIMS: Follicle-stimulating hormone (FSH) is associated with higher risks of metabolic syndrome and diabetes in menopausal women. We aimed to investigate whether FSH was associated with the lipid profile in women older than 55 years. DESIGN: The data were obtained from a cross-sectional study. PARTICIPANTS: Our data were from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (China, including Shanghai and Zhejiang, Jiangxi and Anhui provinces). A total of 1795 women older than 55 years were selected. METHODS: Morning serum sex hormones and lipid profiles were measured. Linear and logistic regression analyses were used to analyse the data. RESULTS: Lower FSH was associated with lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG), total cholesterol (TC)/HDL-C ratio and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (all p for trend <0.05) after adjusting for age and other sex hormones. After further adjustment for body mass index, diabetes and hypertension, the associations of FSH with the lipid profile weakened, but the associations of FSH quartiles with HDL-C and the TC/HDL-C ratio were still significant (both p for trend <0.05). Compared with women in the highest FSH quartile, the odds of low HDL-C (HDL-C<1.04 mmol/L) in women in the lowest FSH quartile were 5.25 (95% CI 1.60 to 17.26) (p for trend <0.05) in the fully adjusted model, and the odds of TC≥6.22 mmol/L, TGs≥2.26 mmol/L and LDL-C≥4.14 mmol/L were not significant. Luteinising hormone did not show a significant association with dyslipidaemia. CONCLUSION: Lower FSH was associated with a worse lipid profile in women older than 55. Diabetes, adiposity and hypertension mostly explained the association of FSH with TGs and the LDL-C/HDL-C ratio but only partially explained the associations of FSH with HDL-C and the TC/HDL-C ratio.

High prevalence of metabolic diseases, liver steatosis and fibrosis among Chinese psychiatric patients.

BACKGROUND: We aimed to investigate the differences of metabolic disorders between the general population and psychiatric patients, with an emphasis on the prevalence and influencing factors of liver fibrosis in psychiatric patients. METHODS: A total of 734 psychiatric patients and 734 general population matched for age, sex, and BMI were enrolled from Shanghai, China. All participants underwent blood pressure, glucose, lipid profile measurements, and anthropometric parameters including body weight, height and waist circumference. FibroScan examinations were also performed on psychiatric patients. Liver steatosis and fibrosis were diagnosed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by professional staff. RESULTS: Compared with the general population, psychiatric patients revealed significantly higher burden of metabolic disorders. The overall prevalence of liver steatosis (CAP ≥ 233 dB/m) and fibrosis (LSM ≥ 7.0 kPa) was 48.7% and 15.5% in psychiatric patients. Psychiatric patients with liver steatosis or fibrosis showed worse metabolic profile. Meanwhile, the prevalence of liver fibrosis was also significantly higher in patients with overweight, central obesity, diabetes, hypertension, metabolic syndrome, and liver steatosis. In logistic regression analyses, age, BMI and visceral adiposity index were independent risk factors for liver fibrosis in psychiatric patients. Additionally, antipsychotic medication was suggested to be associated with an increased risk of liver fibrosis in psychiatric patients with liver steatosis. CONCLUSIONS: Prevalence of liver steatosis and fibrosis is high in Chinese psychiatric patients. Those with antipsychotic polypharmacy and obesity are at high risk, and may benefit from early liver assessment in preventing fibrosis progression.

Recombinant human p53 adenovirus injection combined with Bortezomib inhibits proliferation and promotes apoptosis in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a B-cell malignancy characterized by abnormal proliferation of clonal plasma cells in the bone marrow, the incidence of which has further increased in recent years. In multiple myeloma, wild-type functional p53 is often inactivated or dysregulated. Therefore, this study aimed to investigate the role of p53 knockdown or overexpression in multiple myeloma and the therapeutic effect of recombinant adenovirus-p53 (rAd-p53) in combination with Bortezomib. METHODS: SiRNA p53 and rAd-p53 were used to knock down and overexpress p53. RT-qPCR was used to detect gene expression, and western blotting (WB) was used to detect protein expression levels. We also constructed wild-type multiple myeloma cell line-MM1S cell xenograft tumor models and explored the effects of siRNA-p53, rAd-p53, and Bortezomib on multiple myeloma in vivo and in vitro. H&E staining and KI67 immunohistochemical staining were used to assess the anti-myeloma effects of recombinant adenovirus and Bortezomib in vivo. RESULTS: The designed siRNA p53 effectively led to the knockdown of the p53 gene, while rAd-p53 could significantly achieve p53 overexpression. p53 gene inhibited MM1S cell proliferation and promoted apoptosis of wild-type multiple myeloma cell line MM1S. P53 gene inhibited tumor proliferation in vitro by promoting p21 expression and reducing cell cycle protein B1 expression of MM1S. P53 gene overexpression could inhibit tumor growth in vivo. Injection of rAd-p53 in tumor models inhibited tumor development through p21- and cyclin B1-mediated cell proliferation and apoptosis regulation. CONCLUSIONS: We found that overexpression of p53 inhibits MM tumor cell survival and proliferation in vivo and in vitro. Furthermore, the combination of rAd-p53 and Bortezomib significantly improved the efficacy, which provides a new possibility for more effective treatment of MM.

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light.

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (1 O2 ) for PDT with 808 nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808 nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.

The association between serum vitamin A and NAFLD among US adults varied in different BMI groups: a cross-sectional study.

Background and aims: The association between serum vitamin A (VA) and non-alcoholic fatty liver disease (NAFLD) has not been adequately studied. This study aimed to evaluate the association between them in different BMI groups among US adults. Methods: A cross-sectional study was performed using the 2017-2018 National Health and Nutrition Examination Survey (NHANES) datasets (N = 4.723). Linear/logistic regression, interaction effect and mediation analyses were adopted to analyze the association. Results: NAFLD tended to be more prevalent in adults in the middle and high tertiles of serum VA than in those in the low tertile of serum VA (OR [95% CI], 1.17 [0.94, 1.45] and 1.43 [1.16, 1.75]). In the sensitivity analysis, subjects in the middle or high tertile of serum VA had 10% (OR, 1.10 [0.88, 1.39] and 31% (OR, 1.31 [1.09, 1.58]) higher odds of NAFLD than those in the low tertile of serum VA. In the normal weight group, higher serum VA was associated with 125% and 333% higher odds of NAFLD in the middle and high tertiles, respectively, (OR, 2.25 [1.46, 3.48] and 4.33 [2.43, 7.69]) compared with the low tertile serum VA group. However, serum VA and NAFLD were not significantly associated with the obese group. Among different BMI groups (<30 compared with ≥30), serum triglycerides and insulin resistance mediated the association between VA and NAFLD in adults to varying degrees. Conclusions: In the weighted survey, serum VA was positively associated with the degree of NAFLD, especially in the non-obese population.

Tumor Cell-Responsive Photodynamic Immunoagent for Immunogenicity-Enhanced Orthotopic and Remote Tumor Therapy.

Combining photodynamic therapy (PDT) and immune checkpoint blockades is an efficient method to maximize immunotherapeutic outcome by boosting tumor immunogenicity and modulating the immunosuppressive tumor microenvironment. However, the always-on bioactivity of photosensitizers or immune checkpoint inhibitors leads to uncontrollable side effects, limiting the in vivo therapeutic efficacy of treatments. An activatable strategy is of great importance for improving the selectivity during cancer therapy. In this study, a photodynamic immunomodulator, ICy-NLG, is developed by conjugating the photosensitizer ICy-NH2 with the indoleamine 2,3-dioxygenase 1 inhibitor NLG919 through a glutathione (GSH)-cleavable linker to achieve activatable photodynamic immunotherapy. The conjugation considerably suppresses both the PDT effect and the activity of the inhibitor. After ICy-NLG is activated by high levels of GSH in tumor cells, the PDT effect is restored and leads to immunogenic tumor cell death. The released tumor-associated antigens in conjunction with the activated immune checkpoint inhibitor induce a synergistic antitumor immune response, resulting in the growth inhibition of primary and distant tumors and the prevention of lung metastasis in mouse xenograft models.

Joint exposure to positive affect, life satisfaction, broad depression, and neuroticism and risk of cardiovascular diseases: A prospective cohort study.

BACKGROUND AND AIMS: Psychologic wellbeing can impact cardiovascular health. We aimed to evaluate the joint association of multiple psychologic wellbeing factors with cardiovascular diseases (CVD) and examine whether this association was modified by genetic susceptibility. METHODS: In the UK Biobank, 126,255 participants free of CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) at baseline, who completed a questionnaire on psychological factors, were included. The psychological wellbeing score was calculated by four factors: happiness, life satisfaction, broad depression, and neuroticism. Cox proportional hazard models were used to assess the association between the psychological wellbeing score and CVD risk. RESULTS: During the median follow-up of 11.5 years, 10,815 participants had newly diagnosed CVDs. Low life satisfaction, the presence of depression, and neuroticism score ≥1 were significantly associated with an increased risk of CVD in the multivariable-adjusted model. Through decreasing the psychological wellbeing score, there were significant increasing linear trends in the risk of CVD, CHD, stroke, and HF (all p for trend < 0.001). Participants with the lowest psychological wellbeing score had the highest risk for CVD (HR 1.51, 95% CI 1.42-1.61). Women were more susceptible to worse psychological wellbeing status for CVD than men (p for interaction = 0.009). The associations of the psychological wellbeing score with CVD were consistent across genetic risk (p for interaction >0.05). When considered jointly, participants exposed to high-risk psychological wellbeing and genetic status had a 2.70-fold (95% CI 2.25-3.24) risk for CHD. CONCLUSIONS: Joint exposure to multiple psychological wellbeing factors was associated with increased risks of incident CVD in an additive manner, regardless of genetic susceptibility.

Sleep Duration and Visceral Adipose Tissue: Linear and Nonlinear Mendelian Randomization Analyses.

CONTEXT: Increasing evidence suggests that sleep is important for fat metabolism. However, the causal relationship between sleep duration and visceral adipose tissue (VAT) needs to be further clarified. OBJECTIVE: This study investigated the linear and nonlinear causal association between sleep duration and VAT. METHODS: This study used one-sample and two-sample Mendelian randomization MR). Single-nucleotide polymorphisms (SNPs) associated with sleep duration at genome-wide significance were obtained from published genome-wide association studies. We also recalculated the correlation between each SNP and sleep duration in the UK Biobank. The associations of SNPs with predicted VAT (396 858 participants) were conducted in the UK Biobank. RESULTS: A total of 396 858 eligible participants (54.10% females, 57 ± 8 years old) were included in the study. The participants slept 7.17 ± 1.04 hours and stored 1.25 ± 0.88 kg of VAT on average. Genetically predicted sleep duration was significantly associated with VAT. For each 1-hour increase in genetically predicted sleep duration, the reduction in predicted VAT mass was 0.11 kg (P = 8.18E-16) in total, 0.17 kg (P = 3.30E-11) in men and 0.07 kg (P = 1.94E-06) in women. Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and VAT in all participants, men, and women. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the increased VAT. In contrast, no clear evidence on the causal effect of genetically predicted long sleep duration on VAT mass was found. CONCLUSION: The causal association of sleep duration with VAT was L-type. Our findings support that short sleep duration is a risk factor for increasing VAT, thus reinforcing the probability that increasing sleep duration may decrease VAT.

Trends in Iodine Status Among U.S. Children and Adults: A Cross-Sectional Analysis of National Health and Nutrition Examination Survey Data from 2001-2004 to 2017-2020.

Background: Iodine nutrition is an important public health issue. Trends in iodine status over time among U.S. schoolchildren and adults and factors mediating changes of iodine status were examined. Methods: In this cross-sectional study of National Health and Nutrition Examination Survey (NHANES) data, we estimated trends in the U.S. population using linear regression analyses. Representative samples of U.S. children and adults were enrolled in NHANES 2001-2020. The NHANES cycles were categorized into 5 four-year periods: 2001-2004, 2005-2008, 2009-2012, 2013-2016, and 2017-2020. The final sample sizes of children and adults for analysis were 4288 and 19,661, respectively. The estimated average requirement (EAR) (based on guidelines from the Institute of Medicine), was used to estimate the prevalence rate of inadequate iodine intake. Binary logistic regression analyses were used to investigate the association between iodine status and contributing factors. Results: From 2001-2004 to 2017-2020, among children, urinary iodine concentration (UIC) decreased from 243 to 166 µg/L (ptrend = 0.0057) and prevalence of iodine intake below the EAR rose from 15.4% to 27.6%. In adults, the UIC decreased from 153 to 116 µg/L (ptrend < 0.001) and prevalence of iodine intake below the EAR rose from 15.0% to 17.9%. A higher prevalence rate of iodine intake below the EAR was observed in females compared with males (children, 24.0% vs. 16.5%, p < 0.001; adults, 20.0% vs. 11.1%, p < 0.001). Inadequate iodine intake was less frequent among non-Hispanic White and Hispanic compared with non-Hispanic Black in children and adults. Adults without thyroid problems had a higher prevalence of inadequate iodine intake than those with thyroid problems (16.0% vs. 13.0%, p = 0.001). Inadequate iodine intake was less likely in the children who "sometimes" and "often" consumed milk products compared with children who "never or rarely" consumed milk products (OR = 0.60 [CI 0.30-1.21] and OR = 0.24 [CI 0.13-0.43], respectively). The prevalence of inadequate iodine intake among adults reporting "sometimes" (OR = 0.70 [CI 0.58-0.83]) and "often" consuming milk products was lower than those who "never or rarely" consumed them (OR = 0.36 [CI 0.30-0.44]). Conclusions: In this weighted survey, the prevalence of inadequate iodine intake increased from 2001-2004 to 2017-2020 among U.S. school-age children and adults. Sex, race, thyroid problems, and a decreased intake of milk products were significantly associated with iodine intake below the EAR.

Detection of BRAF V600E in Fine-Needle Aspiration Samples of Thyroid Nodules by Droplet Digital PCR.

Background: BRAF exon 15 p.V600E (BRAF V600E) mutation has been established as an important molecular marker for papillary thyroid carcinoma diagnosis by ultrasound-guided fine-needle aspiration biopsy (FNAB). Sanger sequencing is the gold standard for detecting BRAF V600E mutations but fails to identify low-frequency mutations. However, droplet digital PCR (ddPCR) is a popular new method for detecting low-frequency mutations. Here, we compare the efficiency of droplet digital PCR (ddPCR) and Sanger sequencing for detection of the BRAF V600E mutation in thyroid fine-needle aspiration (FNA) samples. Methods: Thyroid fine-needle aspiration samples from 278 patients with 310 thyroid nodules were collected. Sanger sequencing and ddPCR were conducted to detect the BRAF V600E mutation. Results: The BRAF V600E mutation was found in 94 nodules (30.32%) by ddPCR and 40 nodules (12.90%) by Sanger sequencing in 310 FNA samples. A total of 119 nodules were confirmed PTC by postsurgical pathology. Among which the BRAF mutation was found in 80 (67.23%) nodules by ddPCR and 31 (26.05%) by Sanger sequencing. All nodules carrying the mutation detected by Sanger sequencing (SS+) were verified by ddPCR (ddPCR+). Also, all nodules with no mutation detected by ddPCR were interpreted as wild-type by Sanger sequencing (SS-). In addition. Almost all SS+/ddPCR + nodules (95.00%; 38/40) and SS-/ddPCR + nodules (100.00%; 54/54) displayed a BRAF mutation rate of >5% and <15%, respectively, indicating easy misdetection by Sanger sequencing when the mutation rate is between 5 and 15%. Conclusion: ddPCR has higher sensitivity than Sanger sequencing and we propose ddPCR as a supplement to Sanger sequencing in molecular testing of BRAF using FNAB samples.

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

Purpose: Whether Vitamin D deficiency or insufficiency is associated with thyroid autoimmunity was debated for long time. This study was still to explore the causal relationship of 25 (OH) D with a thyroid peroxidase antibody (TPOAb). Methods: The data were obtained from a cross-sectional study, SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. 10636 participants were finally included in this study. Genotyped four 25 (OH) D-related and four TPOAb-associated single nucleotide polymorphisms (SNPs) created their genetic risk scores (GRS). Bidirectional mendelian randomization (MR) analysis was used in this study. Results: 25 (OH) D GRS was significantly associated with 25 (OH) D (B -0.093, 95% CI -0.111, -0.074) and TPOAb level (B 0.067, 95% CI 0.002 to 0.132). TPOAb GRS was significantly associated with TPOAb concentration (B 0.345, 95% CI 0.135 to 0.556), but not 25 (OH) D (B -0.030, 95% CI -0.091 to 0.030). Using 25 (OH) D_GRS as instrumental variable in the MR analysis, a causal relationship of genetically determined 25 (OH) D with increased TPOAb concentration (B -0.720, 95% CI -1.429 to -0.012). No relation was found between genetically instrumented TPOAb and 25 (OH) D. Conclusion: A higher VD_GRS was associated with higher risk of increased TPOAb concentration, which supports a causal association between decreased vitamin D and increased concentration of TPOAb in an eastern Chinese population.

A five-gene panel refines differential diagnosis of thyroid nodules.

BACKGROUND: Molecular testing for oncogenic mutations in fine-needle aspiration has showed high predictive value in identifying malignant lesions from thyroid nodules with indeterminate cytology. METHODS: To figure out an efficient and economical gene panel for most medical institutions in China, we designed a five-gene panel including BRAF/NRAS/KRAS/HRAS/TERT genes and conducted a retrospective study to evaluate the role of this five-gene diagnostic panel in differential diagnosis of thyroid nodules. RESULTS: A total of 665 patients with 695 thyroid nodules were investigated in the current study. The fine-needle aspiration biopsy and surgically separated thyroid tissue specimens were harvested to test BRAF, TERT, NRAS, KRAS, and HRAS mutations. We identified 261 mutations in 665 patients, including 177 V600E mutations in BRAF. Three hundred and sixty-nine patients who underwent thyroid surgery after completion of the initial clinical and cytological evaluation were enrolled in the final analysis. The diagnostic sensitivity, specificity, and accuracy of the combination of FNAB cytology and five-gene detection were 74.7%, 93.8%, and 84.8%, respectively. BRAF V600E and five-gene panel could recognize 46.4% and 53.6% of papillary thyroid carcinoma in the patients with cytologically indeterminate nodules. CONCLUSION: The five-gene panel can effectively improve the sensitivity, negative predictive value, and accuracy of fine-needle aspiration biopsy cytology, especially in the patients with cytologically indeterminate nodules.

Influence of Rapid Urbanization on Thyroid Autoimmune Disease in China.

BACKGROUND: The prevalence of autoimmune thyroid diseases (AITDs), especially Hashimoto's thyroiditis (HT), has increased dramatically in China. Moreover, China is experiencing the largest scale of urbanization in the world. We intended to explore the relationship between rapid urbanization and HT. METHODS: A total of 2946 subjects in Zhejiang Shangyu (SY) (n = 1546) and Jiangsu Nanjing (NJ) (n = 1400) were enrolled in this study. Serum TPOAb, TGAb, and thyrotropin (TSH) were measured, and ultrasonography of the thyroid was performed in all subjects. DNA was extracted from all subjects, and four SNPs were selected for genotyping. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction between genetic factors and environment factors. RESULTS: TPOAb and TGAb concentrations were higher in NJ than in SY (34.60 vs. 14.00 IU/ml and 21.05 vs. 7.50 IU/ml). People in NJ also had higher TPOAb and TGAb positivity rates than those in SY (7.8% vs. 12.7% and 8.7% vs. 16.3%). Logistic regression analysis indicated that rapid urbanization was an independent risk factor for TPOAb (OR = 1.473) and TGAb (OR = 1.689). Genotype TT in rs11675434 was associated with an increased risk of TPOAb positivity both in SY (OR = 2.955) and in NJ (OR = 1.819). GMDR analysis showed a two-locus model (SNP2 × urbanization) and a three-locus model (SNP2 × SNP3 × urbanization), which had testing accuracies of 56.88% and 57.25%, respectively (P values were 0.001 and 0.001). CONCLUSION: Rapid urbanization influences the incidence of TPOAb and TGAb positivity. We should pay more attention to thyroid autoimmune disease in areas of China experiencing rapid urbanization.

Relationship between Gene Polymorphisms and Urine Iodine Levels on Susceptibility to Thyroid Peroxidase Antibody Positivity in the Chinese Population.

BACKGROUND/AIMS: Hashimoto thyroiditis, characterized by positive thyroid peroxidase antibodies (TPOAbs), is caused by the interaction of genetic and environment factors. The aim of this study was to clarify the interaction of gene polymorphisms and iodine intake in the incidence of TPOAb positivity. METHODS: 1,733 subjects were included in this study. Genomic DNA was extracted from peripheral blood white cells. Four SNPs (rs11675434 [TPO], rs3094228 [HCP5], rs9277555 [HLA-DPB1], and rs301799 [RERE]) were selected for genotyping. Weighted TPOAb genetic risk score (GRS) was calculated based on these 4 SNPs. Thyroid hormones and autoimmune antibodies (TPOAb and thyroglobulin antibody) were determined using the electrochemiluminescence immunoassay method. RESULTS: The mean serum thyrotropin level in TPOAb-positive subjects was higher than in TPOAb-negative subjects (p < 0.01). Genotype GG of rs9277555 was associated with an increased risk of TPOAb positivity (OR = 1.64, 5-95% CI 1.09, 2.47, p = 0.02). Genotype TT of rs11675434 showed marginal increased risk of TPOAb positivity (OR = 1.57, 5-95% CI 1.01, 2.43, p = 0.048). Logistic regression analysis showed TPOAb-GRS and rs9277555 were associated with TPOAb positivity (OR = 5.09, 5-95% CI 1.30, 19.91, p = 0.02 and OR = 1.30, 5-95% CI 1.05, 1.61, p = 0.02). Subjects with a high TPOAb-GRS had a 52% increased risk of TPOAb positivity compared to subjects with a low TPOAb-GRS (OR 1.52, 5-95% CI 1.05, 2.21, p = 0.03). CONCLUSION: TPOAb-GRS was associated with an increased risk of TPOAb positivity in a Chinese Han population. This effect might be attribute to rs9277555.

Blood lead, vitamin D status, and albuminuria in patients with type 2 diabetes.

Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%-15.5%) in diabetic patients with 25(OH)D < 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, -5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03-1.15) and 0.99 (95% CI, 0.86-1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D < 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.

Association between serum vitamin D and uric acid in the eastern Chinese population: a population-based cross-sectional study.

BACKGROUND: Uric acid (UA) is the end product of purine metabolism, which is thought to be related to many human diseases, such as nephrolithiasis, gout, cardiovascular disease (CVD), type 2 diabetes mellitus, metabolic syndrome. However, the relationship between serum UA (SUA) and 25(OH) D is still unclear in the eastern Chinese population. METHODS: We did a population-based observational investigation, which included 12,770 residents living in eastern China. Ultimately, data from 9220 subjects were analyzed. Serum 25(OH) D, SUA, fasting plasma glucose (FPG), fasting insulin, HbA1c and other metabolic parameters were tested. Waist circumference (WC), weight and height were also measured. Questionnaires were collected from these subjects for information on smoking and drinking status. RESULTS: We enrolled 9220 Chinese adults, including 3681 males (age 55.57 ± 13.23 years) and 5539 females (age 54.31 ± 12.83 years). The levels of SUA were 352.07 ± 79.25 nmol/L and 269.29 ± 64.68 nmol/L in males and females, respectively. The proportion of adults with hyperuricemia (HUA) was 12.26% in the total population. Levels of SUA were positively associated with 25(OH) D, and the incidence of HUA increased 9.4% for every 10 nmol/L increase in 25(OH) D (P < 0.001). CONCLUSIONS: SUA was positively associated with 25(OH) D in the eastern Chinese population. Higher levels of serum 25(OH) D may be a potential predictor of HUA.

Prevalence of hyperuricaemia in an Eastern Chinese population: a cross-sectional study.

OBJECTIVES: In the past decade, China has been characterised by large-scale urbanisation as well as rapid economic growth. The aim of this study was to further investigate the prevalence of hyperuricaemia (HUA) in an Eastern Chinese population. DESIGN: Cross-sectional study. SETTING: Survey of Prevalence in East China of Metabolic Diseases and Risk Factors China study. PARTICIPANTS: In this study, 12 770 residents from 22 sites in Eastern China were recruited. Finally, 9225 subjects were included. MAIN OUTCOME MEASURES: The serum levels of uric acid (UA), fasting plasma glucose (FPG), glycated haemoglobin and other metabolic parameters were tested. Waist circumference, weight, height and blood pressure were also measured. Questionnaires regarding smoking, drinking, education were collected from the subjects. HUA was defined as serum UA >420 µmol/L for men and >360 µmol/L for women. RESULTS: The prevalence of HUA in this Eastern Chinese population was 11.3% (9.9, 12.7) overall, 20.7% (17.7, 23.7) in men and 5.6% (4.3, 6.7) in women. The prevalence of HUA in urban subjects was higher than that in rural subjects (12.9 vs 10.8%, p<0.01). The prevalence of HUA was negatively and positively associated with age in men and women, respectively. Residents with high body mass index levels had a higher prevalence of HUA. In the logistic regression analysis, male sex, urban residency, total cholesterol, triglyceride, overweight, obesity, systolic blood pressure and low economic status were independently correlated with HUA. CONCLUSIONS: The estimated prevalence of HUA in this Eastern Chinese population was 11.3% (9.9, 12.7) overall and 20.7% (17.7, 23.7) and 5.6% (4.3, 6.7) in men and women, respectively. HUA has gradually become an important public health issue in China. TRIAL REGISTRATION NUMBER: ChiCTR-ECS-14005052.

Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects.

Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-ß had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-ß going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-ß no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.