Hospitalized patients with isolated distal deep vein thrombosis: anticoagulation therapy or not?

BACKGROUND: Isolated distal deep vein thrombosis (IDDVT), a disease frequently detected in hospitalized patients, can progress to proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Here, we evaluated the effects of anticoagulation in hospitalized IDDVT patients. METHODS: We conducted a retrospective study in our hospital and enrolled hospitalized IDDVT patients diagnosed by compression ultrasonography (CUS) from January to December 2020. Participants were divided into anticoagulation (AC) and non-anticoagulation (non-AC) groups. After propensity score matching (PSM), multivariate Cox regression analyses were performed to assess whether anticoagulation was associated with PDVT/PE, and all-cause mortality. RESULTS: A total of 426 IDDVT inpatients with CUS follow-up were screened from 1502 distal DVT patients and finally enrolled. The median age was 67 years with 51.4% males and 15.5% cancer patients. The median follow-up was 11.6 months. There were 288 and 138 patients treated with or without anticoagulants, respectively. Patients in the non-AC group had less body mass index and more comorbidities. Patients in the AC group were treated with rivaroxaban or dabigatran (52.1%), low molecular weight heparin (42.7%), and warfarin (5.2%). The PSM generated 111 pairs of well-matched IDDVT patients with or without anticoagulation. The Kaplan-Meier analysis demonstrated that neither the incidence of PDVT/PE (5.4% vs. 2.7%, log-rank p = 0.313) nor all-cause mortality (27.9% vs. 18.9%, log-rank p = 0.098) was significant different between groups. Anticoagulation was not associated with PDVT/PE and all-cause mortality in the multivariable Cox regression analyses using the matched cohorts. The main risk factors for all-cause mortality were age, malignancy history, BMI, sepsis, heart failure, and white blood cell (WBC) count. CONCLUSIONS: In hospitalized IDDVT patients, the thrombosis extension rate to PDVT/PE was low. Anticoagulation did not reduce the incidence of thrombosis extension of IDDVT and was not associated with all-cause mortality.

Iodine in household cooking salt no longer plays a crucial role in iodine status of residents in Tianjin, China.

PURPOSE: The contribution of household cooking salt to population iodine status is decreasing in China, the applicability of the coverage rate of iodized salt (IS), proportion of adequately iodized salt (AIS), and salt iodine concentration (SIC) of household cooking salt used for iodine status assessment of residents requires further investigation. METHODS: Through the IDD control project, 16,445 children and 4848 pregnant women were recruited from Tianjin, China and the relationship between the coverage rate of IS, proportion of AIS, SIC, and population iodine status was analyzed. Additionally, through the thyroid health survey project, 856 children with IS or noniodized salt were recruited. The effects of different household cooking salts on individual iodine status and thyroid health were analyzed. RESULTS: After adjusting for confounding factors, no relationship was found between the coverage rate of IS, proportion of AIS, SIC of household cooking salt, and iodine status of children and pregnant women (all P > 0.05). No differences in levels of thyroid function and structural indicators were found in children with different household cooking salts (all P > 0.05). Additionally, no relationship was found between noniodized salt exposure and goiter, overt hyperthyroidism, overt hypothyroidism, thyroid nodules, antibody single positivity, or subclinical hypothyroidism (all P > 0.05). CONCLUSION: Iodine in household cooking salt no longer plays a crucial role in iodine status in Tianjin, China. Other indicators must be identified as beneficial supplements for precise iodine status evaluation not only in Tianjin but also in other large cities in China.

Risk factors for incomplete thrombosis in false lumen in sub-acute type B aortic dissection post-TEVAR.

There is scarce information about the risk factors for incomplete false lumen thrombosis (FLT) among type B aortic dissection (AD) patients, particularly in the sub-acute phase following thoracic endovascular aortic repair (TEVAR). We enrolled consecutive sub-acute type B AD patients at Xinqiao Hospital (Chongqing, China) from May 2010 to December 2019. Patients with severe heart failure, cancer, and myocardial infarction were excluded. The postoperative computed tomography angiography (CTA) data were extracted from the most recent follow-up aortic CTA. Multivariate logistic regressions were applied to identify the association between FLT and clinical or imaging factors. Fifty-five subjects were enrolled in our study. Twelve participants showed complete FLT, and 2 of these died during the follow-up, while 8 patients died in incomplete FLT group. In the multivariate analysis, maximum abdominal aorta diameter (OR 1.20, 95% CI 1.016-1.417 p = 0.032) and the number of branches arising from the false lumen (FL) (OR 15.062, 95% 1.681-134.982 p = 0.015) were significantly associated with incomplete FLT. The C-statistics was 0.873 (95% CI 0.773-0.972) for the model. The FL diameter (p < 0.001) was significantly shorter following TEVAR, while the true lumen diameter (p < 0.001) and maximum abdominal aorta diameter (p = 0.011) were larger after the aortic repair. There were 21.8% of sub-acute type B AD patients presented complete FLT post-TEVAR. Maximum abdominal aorta diameter and the number of branches arising from the FL were independent risk factors for incomplete FLT. The true lumen diameter, maximum abdominal aorta diameter, and FL diameter changed notably following TEVAR.

Health risks of PM2.5-bound polycyclic aromatic hydrocarbon (PAH) and heavy metals (PPAH&HM) during the replacement of central heating with urban natural gas in Tianjin, China.

To investigate the health effects of fine particulate matter (≤ 2.5 µm in aerodynamic diameter; PM2.5)-bound heavy metals and polycyclic aromatic hydrocarbons (PAHs) before and after the implementation of the Urban Natural Gas Heating Project (UNGHP), the lifetime cancer risks, hazard quotients (HQs) of heavy metals and PAHs were calculated. Seven kinds of heavy metals (Al, As, Cd, Cr, Mn, Ni and Se) and 12 kinds of PAHs including acenaphthylene (ANY), acenaphthene (ANA), fluoranthene (FLT), pyrene (PYR), chrysene (CHR), benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), dibenz[a,h]anthracene (DBA), benzo[ghi]perylene (BPE) and indeno[1,2,3-cd]pyrene (IPY) were analyzed and used for the health risk assessments. It was found that HQ of Mn fell from 1.09 in the coal-burning period to 0.72 in the gas-burning period in the suburban area. And lifetime cancer risks of PAHs fell from 35.7 × 10-6 in the coal-burning period to 17.22 × 10-6 in the gas-burning period in the urban area. It could be concluded that, during the gas-burning period, downward trends were observed for the lifetime cancer risks and HQs of most kinds of heavy metals and PAHs in all regions of Tianjin compared to those during the coal-burning period. The UNGHP was effective, and we should also take other measures to control the pollution.

Fluoride exposure, dopamine relative gene polymorphism and intelligence: A cross-sectional study in China.

BACKGROUND: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear. OBJECTIVES: We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water. METHODS: We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment. RESULTS: In adjusted model, fluoride exposure was inversely associated with IQ scores (ß = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107). CONCLUSIONS: Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.

Interactive effect between temperature and fine particulate matter on chronic disease hospital admissions in the urban area of Tianjin, China.

This study focuses on effects of fine particulate matter (PM2.5) on chronic disease under different levels of temperature. We obtained type 2 diabetes, cerebral stroke and coronary heart disease hospital admissions (HAs) from five hospitals in urban Tianjin as well as the concentrations of PM2.5, nitrogen dioxide (NO2) and sulphur dioxide (SO2). We used distributed lag nonlinear models to explore nonlinear and lag effects of PM2.5. In single-pollutant models, PM2.5 was positively associated with type 2 diabetes, cerebral stroke and coronary heart disease HAs, with strongest effects at lag1, lag0 and lag06, respectively. The corresponding relative risk rates (RR%) were 1.836%, 2.083% and 6.428%. In co-pollutant models, the correlation between PM2.5 and HAs on high-temperature days was generally stronger than that on low-temperature days. This study indicated that PM2.5 can increase HA rates for these chronic diseases, and effects of PM2.5 on high-temperature days were stronger than that on low-temperature days.

Stopping the supply of iodized salt alone is not enough to make iodine nutrition suitable for children in higher water iodine areas: A cross-sectional study in northern China.

BACKGROUND: For the sake of children's health, iodized salt supply has been stopped in many areas with excessive iodine in the drinking water, but children's iodine nutrition status and thyroid function after terminating the iodized salt supply is unknown. Objective We assessed the iodine nutrition, thyroid function and influencing factors for thyroid abnormalities in children from areas with different concentrations of water iodine; the supply of iodized salt has been stopped in high water iodine areas. This study aimed to evaluate whether the strategy of stopping the supplies of iodized salt alone is enough to avoid thyroid dysfunction in all areas with excess water iodine while still meeting the iodine nutrition needs of children. METHODS: A cross-sectional study was conducted in children from four areas with different drinking water iodine concentrations in Tianjin, China. The drinking water samplings and spot urine samples were collected to estimate the external and internal iodine exposure levels. The thyroid volume was measured, and blood samples were collected to assess thyroid function. Logistic regression analysis was used to analyze risk factors for thyroid abnormalities. A dietary survey was conducted to determine the sources of iodine nutrition among the areas with different iodine concentrations in the drinking water. RESULTS: In the area with a drinking water iodine concentration ≥300 µg/L, the median urinary iodine concentration (UIC) in children was 476.30 (332.20-639.30) µg/L, which was higher than that in other groups (all P < 0.05), and the prevalence of thyroid nodules and the thyroid goiter rate were higher than those in the <100 µg/L, 100-150 µg/L and 150-300 µg/L areas (all P < 0.01). Binary logistic regression analysis indicated that the risk of thyroid abnormalities was significantly increased in the UIC 200-299 µg/L group (OR: 4.534; 95% CI: 1.565, 13.135; bootstrapped 95% CI: 1.689, 21.206, P = 0.004) and in the UIC ≥ 300 µg/L group (OR: 6.962; 95% CI: 2.490, 19.460; bootstrapped 95% CI: 2.838, 32.570, P = 0.001) compared to the 100-199 µg/L group. The iodine contribution rates from water in areas with water iodine concentrations ≥300 µg/L are up to 63.04%. CONCLUSIONS: After termination of the iodized salt supply, the level of iodine nutrition of children in the area with drinking water iodine concentrations ≥300 µg/L is still excessive. The water source needs to be replaced in this area. In the area with a water iodine concentration of 150-300 µg/L, it is proposed that stopping the supply of iodized salt is sufficient to achieve the proper iodine nutrition status in children.

How the constituents of fine particulate matter and ozone affect the lung function of children in Tianjin, China.

As the pollution of fine particulate matter (≤ 2.5 µg/m3 in aerodynamic diameter; PM2.5) and ozone (O3) is becoming more and more serious in developing countries, we, hereby, investigated the effects of PM2.5, constituents of PM2.5 and O3 on the lung function of children in Tianjin, China. The lung functions of 198 pupils from nine primary schools in Tianjin were examined (repeated five times) during the months of October to December in 2016, 2017 and 2018, respectively. And the mixed-effect models were used to evaluate the effects of air pollutants. A 10 µg/m3 increase in PM2.5 and O3-8h might lead to reductions of forced vital capacity (FVC) in 1.03% (- 1.87 to - 0.19%) and 21.09% (- 25.54 to - 16.58%), respectively, while a 10 ng/m3 increment in ANY might account for the 166.44% (- 221.32 to - 112.31%) decreases in FVC. PM2.5 and O3-8h might be more harmful to the lung functions of female students and participants with PS exposure at home. And the main sources of pollution resulting in the decrease in pulmonary function might be traffic pollution and coal combustion.

Elevated S100A4 in asthmatics and an allergen-induced mouse asthma model.

The elevated S100A4 level has been found in some inflammatory diseases. However, the expression and role of S100A4 in asthma is unknown. The expression of S100A4 in induced sputum and plasma from healthy control and asthmatics were assessed by ELISA. Then an allergen-induced asthma mouse model treatment with anti-S100A4 antibody was used to explore the role of S100A4 in the pathogenesis of asthma. The S100A4 levels in sputum not in plasma in asthmatics were significantly increased than those of healthy controls and were negatively correlated with some lung function parameters and were positively correlated with sputum eosinophilia and lymphocyte. The expression of S100A4 in the lung as well as in BALF were also significantly higher in the asthma mouse model and treatment with anti-S100A4 antibody exhibited reductions in inflammatory cell accumulation, inflammatory mediators, and airway hyper-responsiveness. We further showed that LY294002, a specific inhibitor of PI3K, markedly decreased S100A4 expression in lung and S100A4 secretion in BALF in asthmatic mice. In conclusion, these data demonstrated that S100A4 may be involved in the pathogenesis of airway inflammation in asthma.

Low-to-moderate fluoride exposure in relation to overweight and obesity among school-age children in China.

High fluoride exposure has been related to harmful health effects, but the impacts of low-to-moderate fluoride on child growth and obesity-related outcomes remain unclear. We performed a large-scale cross-sectional study to examine the association between low-to-moderate fluoride in drinking water and anthropometric measures among Chinese school-age children. We recruited 2430 resident children 7-13 years of age, randomly from low-to-moderate fluorosis areas of Baodi District in Tianjin, China. We analyzed the fluoride contents in drinking water and urine samples using the national standardized ion selective electrode method. Multivariable linear and logistic analyses were used to assess the relationships between fluoride exposure and age- and sex-standardized height, weight and body mass index (BMI) z-scores, and childhood overweight/obesity (BMI z-score > 1). In adjusted models, each log unit (roughly 10-fold) increase in urinary fluoride concentration was associated with a 0.136 unit increase in weight z-score (95% CI: 0.039, 0.233), a 0.186 unit increase in BMI z-score (95% CI: 0.058, 0.314), and a 1.304-fold increased odds of overweight/obesity (95% CI: 1.062, 1.602). These associations were stronger in girls than in boys (Pinteraction = 0.016), and children of fathers with lower education levels were more vulnerable to fluoride (Pinteraction = 0.056). Each log unit (roughly 10-fold) increase in water fluoride concentration was associated with a 0.129 unit increase in height z-score (95% CI: 0.005, 0.254), but not with other anthropometric measures. Our results suggest low-to-moderate fluoride exposure is associated with overweight and obesity in children. Gender and paternal education level may modify the relationship.

3-Methyladenine alleviates excessive iodine-induced cognitive impairment via suppression of autophagy in rat hippocampus.

Drinking water with high levels of iodine has been identified as the key contributor to iodine excess, but the mechanisms of neurotoxicity induced by excessive iodine remain elusive. The present study aimed to explore the role of autophagy in the neurotoxic effect induced by excessive iodine in vivo. The Morris water maze test results demonstrated that excessive iodine impaired the learning and memory capabilities of rats, which were associated with marked body weight and brain weight abnormalities. In addition, iodine treatment increased malondialdehyde accumulation, decreased superoxide dismutase activity and glutathione (GSH) level, and enhanced levels of autophagy markers in the hippocampus. Notably, inhibition of autophagy with 3-methyladenine (3-MA) could significantly alleviate excessive iodine-induced cognitive impairment. These data imply that autophagy is involved in the cognitive impairment elicited by excessive iodine as a pathway of cell death, and inhibition of autophagy via 3-MA may significantly alleviate the above damage.

Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence impairment of children in China: A school-based cross-sectional study.

OBJECTIVE: We aimed to study the association of urine fluoride with intelligence quotient (IQ) in children with a careful consideration of up to 30 potential confounding factors as well as possible heterogeneity of the relation between urine fluoride levels and IQ scores across children with different dopamine receptor-2 (DRD2) Taq 1A genotypes (CC, CT, and TT). METHODS: A school-based cross-sectional study design was applied. A total of 323 children (2014-2015, 7-12 years old) were enrolled from four schools in both historical endemic and non-endemic areas of fluorosis in Tianjin of China using a cluster sampling method. Urine fluoride levels and age-specific IQ scores in children were measured at the enrollment. Polymerase chain reaction-restriction fragment length polymorphism methods were used to genotype DRD2 Taq 1A polymorphism with genomic DNA isolated from whole blood collected at the enrollment. Multiple linear regression models were applied to evaluate the relationship between urine fluoride levels and IQ scores overall and within the DRD2 Taq 1A SNP = CC/CT and TT subgroups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques. A safety threshold of urine fluoride levels for IQ impairment was determined in the subgroup TT. RESULTS: In overall participants, the DRD2 Taq 1A polymorphism itself was not related to IQ scores in children who had a high level of urine fluoride. In the CC/CT subgroup, urine fluoride levels and IQ scores in children were unrelated (adjusted ß (95% confidence interval (CI)) = - 1.59 (- 4.24, 1.05), p = 0.236). Among the participants carrying the TT genotype, there was a strong and robust negative linear relationship between log-urine fluoride and IQ scores in children (adjusted ß (95% CI) = - 12.31 (- 18.69, - 5.94), p < 0.001). Urine fluoride levels had a stronger association with IQ in children carrying the TT genotype (adjusted ß = - 12.31, bootstrapped standard error (SE) = 1.28), compared to that in overall participants (adjusted ß = - 2.47, bootstrapped SE = 3.75) (Z = 2.483 and bootstrapped p = 0.007). The safety threshold of urine fluoride levels in the subgroup TT was 1.73 mg/L (95% CI = (1.51, 1.97) (mg/L)). CONCLUSIONS: There is heterogeneity in the relation between urine fluoride and IQ across children carrying different DRD2 Taq 1A genotypes. Large-scale epidemiological studies are needed to confirm our findings.

Oxidative stress-mediated autophagic cell death participates in the neurotoxic effect on SH-SY5Y cells induced by excessive iodide.

Excessive iodide could induce intellectual damage in children, which has attracted broad attention. To investigate the neurotoxic effect of iodide and its mechanism, a human dopaminergic neuroblastoma cell line (SH-SY5Y) was treated with different concentrations of potassium iodide (KI). The results showed that excessive iodide could decrease cell viability, reduce glutathione (GSH) and superoxide dismutase (SOD), and increase the degree of autophagy (by changing the cellular ultrastructure and raising the autophagy-related mRNA and protein expression of LC3, Beclin1, and p62), which were correlated with the immunofluorescence labeling. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3MA), antioxidant N-acetylcysteine (NAC) and 30 mM KI for 24 h was conducted in the following research. 3MA significantly decreased autophagy-related mRNA and protein expression and improved cell viability, indicating that excess iodide induced autophagic cell death. In addition, oxidative stress regulated autophagy, reflected by the results that NAC decreased the mRNA and protein expression of LC3, Beclin1, and p62. In summary, autophagic cell death mediated by oxidative stress may participate in excessive iodide-induced SH-SY5Y cell death.

HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2.

The proinflammatory factor high mobility group box protein 1 (HMGB1) has been implicated as an important mediator of many chronic inflammatory diseases, including asthma. Human bronchial epithelial cells (HBECs) play a central role in the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the underlying mechanisms remain unknown. Here, we investigated receptor expression and proinflammatory cytokine production by primary cultures of HBECs stimulated by HMGB1. We then examined the effects of specific receptor blockade and inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF-α, TSLP, MMP-9, and VEGF in a dose- and time-dependent manner. HMGB1 also induced elevated expression of RAGE protein. Secretion of TNF-α, VEGF, MMP-9, and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition. These observations suggest that HMGB1 binds RAGE and promotes activities of p38 MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF-α, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in asthma. These results demonstrate that HMGB1 enhances the inflammatory responses of HBECs, which are involved in the modulation of inflammatory processes in asthma.

Predicting Hospital Readmissions in Patients Receiving Novel-Dose Sacubitril/Valsartan Therapy: A Competing-Risk, Causal Mediation Analysis.

Backgrounds: Our study aimed to identify and predict patients with heart failure (HF) taking novel-dose Sacubitril/Valsartan (S/V) at risk for all-cause readmission, as well as investigate the possible role of left ventricular reverse remodeling (LVRR). Methods and results: There were 464 patients recruited from December 2017 to September 2021 in our hospital with a median follow-up of 660 days (range, 17-1494). Competing risk analysis with Gray's Test showed statistically significant differences in all-cause readmission (p-value< .001) across the three different dose groups. Models 1 and 2 were developed based on the results of univariable competing risk analysis, least absolute shrinkage and selection operator approach, backward stepwise regression, and multivariable competing risk analysis. The internal verification (data-splitting method) indicated that Model 1 had better discrimination, calibration, and clinical utility. The corresponding nomogram showed that patients aged 75 years and above, or taking the lowest-dose S/V (≤50 mg twice a day), or diagnosed with ventricular tachycardia, or valvular heart disease, or chronic obstructive pulmonary disease, or diabetes mellitus were at the highest risk of all-cause readmission. In the causal mediation analysis, LVRR was considered as a critical mediator that negatively affected the difference of novel-dose S/V in readmission. Conclusions: A significant association was detected between novel-dose S/V and all-cause readmission in HF patients, in part negatively mediated by LVRR. The web-based nomogram could provide individual prediction of all-cause readmission in HF patients receiving novel-dose S/V. The effects of different novel-dose S/V are still needed to be explored further in the future.

Impact of coronary artery disease in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atherosclerotic coronary artery disease (CAD) often occurs concurrently with hypertrophic cardiomyopathy (HCM). However, the influence of concomitant CAD has not been fully assessed in patients with HCM. METHODS: Invasive or computed tomography coronary angiography was performed in 461 patients with HCM at our hospital to determine the presence and severity of CAD from March 2010 to April 2022. The primary end points were all-cause, cardiovascular, and sudden cardiac deaths. The survival of HCM patients with severe CAD was compared with that of HCM patients without severe CAD. RESULTS: Of 461 patients with HCM, 235 had concomitant CAD. During the median (interquartile range) follow-up of 49 (31-80) months, 75 patients (16.3%) died. The 5-year survival estimates were 64.3%, 82.5%, and 86.0% for the severe, mild-to-moderate, and no-CAD groups, respectively (log-rank, p = 0.010). Regarding the absence of cardiovascular death, the 5-year survival estimates were 68.5% for patients with severe CAD, 86.4% for patients with mild-to-moderate CAD, and 90.2% for HCM patients with no CAD (log-rank, p = 0.001). In multivariate analyses, severe CAD was associated with all-cause and cardiovascular death after adjusting for age, left ventricular ejection fraction, hypertension, and atrial fibrillation. CONCLUSIONS: This study showed a worse prognosis among HCM patients with severe CAD than among HCM patients without severe CAD. Therefore, timely recognition of severe CAD in HCM patients and appropriate treatment are important.

Miz1 promotes KRAS-driven lung tumorigenesis by repressing the protocadherin Pcdh10.

Targeting KRAS-mutated non-small-cell lung cancer (NSCLC) remains clinically challenging. Here we show that loss of function of Miz1 inhibits lung tumorigenesis in a mouse model of oncogenic KRAS-driven lung cancer. In vitro, knockout or silencing of Miz1 decreases cell proliferation, clonogenicity, migration, invasion, or anchorage-independent growth in mutant (MT) KRAS murine or human NSCLC cells but has unremarkable impact on non-tumorigenic cells or wild-type (WT) KRAS human NSCLC cells. RNA-sequencing reveals Protocadherin-10 (Pcdh10) as the top upregulated gene by Miz1 knockout in MT KRAS murine lung tumor cells. Chromatin immunoprecipitation shows Miz1 binding on the Pcdh10 promoter in MT KRAS lung tumor cells but not non-tumorigenic cells. Importantly, silencing of Pcdh10 rescues cell proliferation and clonogenicity in Miz1 knockout/knockdown MT KRAS murine or human tumor cells, and rescues allograft tumor growth of Miz1 knockout tumor cells in vivo. Miz1 is upregulated in MT KRAS lung tumor tissues compared with adjacent non-involved tissues in mice. Consistent with this, Miz1 is upregulated while Pcdh10 is downregulated in human lung adenocarcinomas (LUAD) compared with normal tissues, and high Miz1 levels or low Pcdh10 levels are associated with poor survival in lung cancer patients. Furthermore, the Miz1 signature is associated with worse survival in MT but not WT KRAS LUAD, and Pcdh10 is downregulated in MT compared to WT KRAS LUAD. Taken together, our studies implicate the Miz1/Pcdh10 axis in oncogenic KRAS-driven lung tumorigenesis.

[Studies of fluoride on the thyroid cell apoptosis and mechanism].

OBJECTIVE: To explore the toxic effect of fluoride on the human thyroid cells (Nthy-ori 3-1) and its mechanism. METHODS: Nthy-ori 3-1 cells were exposed to 0.0, 0.1, 1.0, 3.0 mmol/L of sodium fluoride (NaF) in vitro. After 24 hours incubation, 3 (4,5-Dimethylthiazol-z-yl)-3, 5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to measure cell viability and the LDH leakage rate. Reactive oxygen species (ROS) level, constituent ratio of the cell cycle, and apoptosis rate were measured by flow cytometry. RESULTS: Comparing to viability of control group (set as 100.00%), the cell viability of the 1.0, 3.0 mmol/L fluoride-treated groups (76.64 +/- 9.13)%, (64.04 +/- 6.32)% were significantly decreased (all P values <0.01). LDH leakage rate and ROS level of the 3.0 mmol/L fluoride-treated group ((48.66 +/-7.15)%, (29993.50 +/- 1786. 86) FI) were significantly increased (all P values <0.01) compared to control group ((35.24 +/- 3.02)%, (13021.33 +/- 1067.55) FI). The G0/G1 phase cells of the 1.0 mmol/L fluoride-treated group ((40.76 +/- 5.65)%) were lower than control group (60.09 +/- 1.76)% (P < 0.01), yet the percentage of cells in S phase ((54.05 +/- 4.59)%) were higher than the control group (32.59 +/- 2.43) % (P < 0.01). Comparing to control group ((9.64 +/- 3.44)%), the percentage of apoptosis cells increased in the 3.0 mmol/L fluoride-treated group ((20.09 +/- 3.22)%) (P < 0.01). CONCLUSION: To Nthy-ori 3-1 cells, fluoride under experimental concentrations decreases cell viability, improve the LDH leakage rate, and ROS level. It blocks the cells in S phase and induce cell apoptosis.

Effects of air pollution and green spaces on impaired lung function in children: a case-control study.

The occurrences of impaired lung function during childhood could substantially influence the health states of the respiratory system in adults. So, the effects of air pollution and green spaces on impaired lung function in children were investigated in this study. The lung function of each student was tested every year from 2015 to 2017 and the method of case-control study was applied. 2087 students aged from 9 to 11 years old of primary schools in Tianjin were ultimately included in this study. The method of propensity score matching (PSM) was performed to minimize the confounding bias and the conditional logistic regression model was carried out to evaluate the effects of indoor and outdoor environmental risk factors on the occurrences of impaired lung function in children. For every interquartile range (IQR) increase in the mixture of six air pollutants at the lag1, lag2, and lag3 periods, the risks of getting impaired lung function were increased by 53.4%, 34.7%, and 16.9%, respectively. The protective effect of greenness at lag2 period (odds ratios (OR)) = 0.022 (95% confidence interval (CI): 0.008-0.035)) was stronger than that at lag1and lag3 periods, respectively. Separate and combined effects of most air pollutants at different lag periods exerted hazardous effects on the lung function of students. Exposure to greenness had protective effects on the lung health of children.

Moderating Role of TSHR and PTPN22 Gene Polymorphisms in Effects of Excessive Fluoride on Thyroid: a School-Based Cross-Sectional Study.

We aimed to investigate the relationship between the effects excessive of fluoride on thyroid health in children and the moderating role of thyroid stimulating hormone receptor (TSHR) or protein tyrosine phosphatase nonreceptor-22 (PTPN22) gene polymorphisms. Four hundred thirteen children (141 with dental fluorosis and 198 boys) were enrolled from both historical endemic and non-endemic areas of fluorosis in Tianjin, China. The fluoride exposure levels, thyroid health indicators, and TSHR (rs2268458) and PTPN22 (rs3765598) polymorphisms were examined. Multiple logistic models were applied to evaluate the relationship between dental fluorosis and thyroid abnormalities. Children over 9 year old with dental fluorosis have lower FT4 and TGAb levels and thyroid volume and higher TPOAb levels (all P < 0.05). In overall participants, children with dental fluorosis were more likely to have thyroid antibody single positive issues (adjusted P = 0.039) and less likely to have a goiter according to age or body surface area (age or BSA) (adjusted P = 0.003); In the TSHR (rs2268458) SNP = CC/CT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may cause thyroid antibody single positive (adjusted P = 0.036; adjusted P = 0.002); in the TSHR (rs2268458) SNP = TT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may protect children from goiter (age or BSA) (adjusted P = 0.018; adjusted P = 0.013). Excessive fluoride may induce thyroid antibody single positive and reduce goiter in children. Heterogeneity exists in the relationship between excessive fluoride and thyroid antibody single positive or goiter issues across children carrying different TSHR (rs2268458) or PTPN22 (rs3765598) genotypes.