The changing health effects of air pollution exposure for respiratory diseases: a multicity study during 2017-2022.

BACKGROUND: Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. METHODS: We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. RESULTS: Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1-0.7%) and 1.4% (1.0-1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5-0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5-1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8-30.3%) and 12.7% (10.8-14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. CONCLUSIONS: Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.

Long noncoding RNA HOXD-AS1 induces epithelial-mesenchymal transition in breast cancer by acting as a competing endogenous RNA of miR-421.

Breast cancer (BCa) is the most common malignant tumor in females. Long noncoding RNAs (lncRNAs) are deregulated in many types of human cancers, including BCa. The purpose of the present study was to examine the expression profile and biological role of HOXD cluster antisense RNA 1 (HOXD-AS1) in BCa. Our results revealed that HOXD-AS1 was upregulated in BCa tissues and cell lines, and high HOXD-AS1 expression was correlated with aggressive clinicopathological characteristics of BCa patients. Further gain-of-function and loss-of-function analysis showed that HOXD-AS1 overexpression promoted, whereas HOXD-AS1 knockdown inhibited BCa cell proliferation, cell cycle progression, migration, and invasion, indicating that HOXD-AS1 may function as a novel oncogene in BCa. Mechanistically, HOXD-AS1 could activate epithelial-mesenchymal transition (EMT) in BCa cells. We further proved that HOXD-AS1 might serve as a competing endogenous RNA of miR-421 in BCa cells, and miR-421 was downregulated and negatively correlated with HOXD-AS1 expression in BCa tissues. Besides, we confirmed that SOX4, a master regulator of EMT, was a direct target gene of miR-421. Further, rescue experiments suggested that miR-421 overexpression partly abrogated the oncogenic role of HOXD-AS1 in BCa cells. Therefore, we shed light on that HOXD-AS1/miR-421/SOX4 axis may be considered as a novel therapeutic target for the treatment of BCa patients.

Shear Wave Elastography Imaging for the Features of Symptomatic Carotid Plaques: A Feasibility Study.

OBJECTIVES: Shear wave elastography (SWE) was performed to evaluate the Young's modulus of carotid plaques in patients presenting with cerebrovascular incidents, to estimate the clinical value and feasibility of this approach. METHODS: Sixty-one patients (mean age, 65 years; 45 men) underwent common duplex ultrasonic examination and SWE evaluation. The patients were divided into the symptomatic and asymptomatic groups based on the presence of unilateral focal neurological symptoms. Elasticity and echogenicity of the carotid plaque was assessed by Young's modulus and Gray-Weale classification, respectively. RESULTS: A total of 271 carotid plaques were assessed through duplex ultrasonic examination and SWE imaging. The Bland-Altman test revealed a perfect reproducibility of Young's modulus measurement using SWE. The interframe coefficient of variation was 16% within the 271 plaques. In the 61 representative plaques, significant correlations were found between Gray-Weale classification and mean Young's modulus (r = 0.728, P < .01) when the confounding factors were controlled. The mean Young's modulus of representative plaques in symptomatic group was lower than those in asymptomatic groups (mean Young's modulus: 81 kPa versus 115 kPa; P < .01). Logistic regression combined with receiver operating characteristic analysis suggested increased sensitivity and specificity for the identification of symptomatic carotid plaques when the mean Young's modulus was combined with stenosis rate. CONCLUSIONS: Shear wave elastography can evaluate the Young's modulus of carotid plaque stably, and could serve as an additional method for the detection of symptomatic carotid plaques, which, in combination with common ultrasound, can promote the efficiency of differentiating symptomatic carotid plaques.

Estimating neighborhood-based mortality risk associated with air pollution: A prospective study.

Effect modification of integrated neighborhood environment on associations of air pollution with mortality remained unclear. We analyzed data from UK biobank prospective study (n = 421,650, median 12.5 years follow-up) to examine disparities of mortality risk associated with air pollution among varied neighborhood settings. Fine particulate matter (PM2.5), PM10 and nitrogen dioxide (NO2) were measured and assigned to each participants' address. Diverse ecological and societal settings of neighborhoods were integrated with principal component analysis and categorized into disadvantaged, intermediate and advantaged levels. We estimated mortality risk associated with air pollution across diverse neighborhoods using Cox regression. We calculated community-level proportions of mortality attributable to air pollutants. There was evidence of higher all-cause and respiratory disease mortality risk associated with PM2.5 and NO2 among those in disadvantaged neighborhoods. In disadvantaged communities, air pollutants explained larger proportions of deaths and such disparities persisted over past decades. Across 2010-2021, reducing PM2.5 and NO2 to 10 µg/m3 (World Health Organization limits) would save 87,000 (52,000-120,000) and 91,000 (37,000-145,000) deaths of populations aged ≥ 40 years, with 150 000 deaths occurred in disadvantaged neighborhood settings. These findings suggested that disadvantaged neighborhoods can exacerbate mortality risk associated with air pollution.

Associations between ecological diversity and rodent plague circulation in Yunnan Province, China, 1983-2020: A data-informed modelling study.

BACKGROUND: Following its resurgence in 1982, rodent plague has been linked to a wide range of circulation risks in Yunnan Province. The most serious public health concern associated with effective plague control is determining how various ecological variables influence the differential risk of transmission. METHODS: We investigated the population dynamics of the hosts and vectors using large-scale epidemiological surveillance data. In a seasonal eco-epidemiological model, we evaluated the impact of ecological conditions on the vectored flea index (VFI) to determine the rate of plague transmission. RESULTS: The findings revealed a changing species composition in natural foci over time. Additionally, shifting distributional ranges of species by elevation may be vital in modulating the VFI. The model estimates indicate that the dynamic VFI contributes to spatiotemporal variance in transmission. CONCLUSIONS: The VFI could be a critical ecological indicator, allowing for real-time tracking and prompt intervention in the circulation of rodent plague. Understanding eco-epidemiological diversity can provide essential insights into effective responses to future plague resurgence.

Changing Iodine Status and the Incidence of Thyroid Disease in Mainland China: A Prospective 20-Year Follow-Up Study.

Background: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow-up. Methods: The original prospective cohort study, started in 1999 (n = 3761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine, and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared with Zhangwu, in which iodine status changed from more than adequate to adequate iodine (from 214 to 167.2 µg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UICs), serum thyroid hormone concentration, and thyroid antibodies were measured. Results: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88 to 141.9 µg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody, positive thyroglobulin antibody (TgAb), and goiter decreased significantly (p < 0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared with the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p < 0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634 to 266.7 µg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter (p < 0.05 for all) were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p < 0.001) was seen. Conclusions: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders.

The effects of microRNA-126 reduced inflammation and apoptosis of diabetic nephropathy through PI3K/AKT signalling pathway by VEGF.

Gene expression microarray and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of miR-126. In model of diabetic nephropathy, we demonstrated that miR-126 expression was down-regulated, compared with control group. Down-expression of miR-126 promoted cell apoptosis and increased inflammation (as indicated by the levels of IL-1ß, IL-6, IL-18 and TNF-α) of diabetic nephropathy in vitro. miR-126 over-expression led to significant inhibition of cell apoptosis and suppressed inflammation (IL-1ß, IL-6, IL-18 and TNF-α). However, the down-expression of miR-126 suppressed the protein expression of VEGF, PI3K and p-AKT in diabetic nephropathy in vitro. On the contrary, over-expression of miR-126 induced the protein expression of VEGF, PI3K and p-AKT in diabetic nephropathy in vitro. The inhibition of VEGF increased the effect of miR-126 down-expression on apoptosis and inflammation in diabetic nephropathy in vitro. We investigated the specific function of miR-126 in patients with diabetic nephropathy and its possible mechanism.

Computer-assisted ultrasound quantification analysis in fatty liver model of rats.

BACKGROUND: Early detection of nonalcoholic fatty liver disease (NAFLD) shows its significant efficacy in preventing the patients from liver failure. The ultrasonic image quantitative analysis software can assist to diagnose NAFLD in the clinical studies. In this study, we aim to explore new method to evaluate the value of computer-assisted ultrasound in diagnosis and classification of fatty liver via Image J software. METHODS: Forty Sprague-Dawley rats were randomly divided into control group (n=10) and model group (n=30). For model group, the rats received high fat diet and subcutaneous injection of carbon tetrachloride to establish nonalcoholic fatty liver model. Ultrasound and pathological examinations on rats were performed on 4, 8, and 12 weeks. Image J software was used to measure the liver grayscale value (LGV) and renal grayscale value (RGV). The difference between LGV and RGV (LRGV) was analyzed. The diagnostic performance of computer-assisted ultrasound quantification was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: We compared ultrasonic quantization parameters between control and model groups and found that the LGV and LRGV were statistically different between the normal and light fatty livers, light and moderate fatty livers, as well as moderate and severe fatty livers, respectively (P<0.05). There was no significant difference in RGV among these groups (P>0.05). Kappa statistic and Bland-Altman analyses showed the consistency of ultrasonic examination and pathological examination was good in diagnosis of fatty liver. CONCLUSIONS: This study indicated that the computer-assisted ultrasound quantification analysis, with high performance of NAFLD diagnosis like pathological examination, could provide a new and flexible noninvasive method for preclinical pharmacological research and basic research.

Current Iodine Nutrition Status and Prevalence of Thyroid Disorders in Tibetan Adults in an Oxygen-Deficient Plateau, Tibet, China: A Population-Based Study.

Background: Iodine deficiency (ID) is a global problem in individuals living in an iodine-deficient environment, specifically in mountainous regions. However, data regarding the iodine nutritional status of Tibetan people in the plateau are limited. Methods: A population-based survey was conducted from July 2016 to July 2017 in Lhasa, Tibet, including 12 communities in Lhasa city and 10 surrounding rural areas. The iodine nutritional status of Tibetan people was evaluated using the traditional iodine nutrition indexes: urinary iodine concentration (UIC), thyroid size, serum thyroxine, thyrotropin, thyroglobulin antibody and thyroid peroxidase antibody (TPOAb). Results: A total of 2295 healthy participants were screened, and 2160 participants who had completed all the required examinations were enrolled in this study (response rate, 94.1%). Urinary iodine showed a skewed distribution, with a median (upper and lower quartiles) of 154 (99-229) µg/L. The percentages of low iodine (UIC <100 µg/L), adequate iodine (UIC, 100-199 µg/L), and high iodine (UIC ≥200 µg/L) were 25.6%, 42.0%, and 32.4%, respectively. The urinary iodine level in the urban region was higher than that in the rural region (p < 0.05). Urinary iodine levels were lower with increasing age (p < 0.05). The prevalence of hyperthyroidism, hypothyroidism, goiter, TPOAb positivity, and thyroglobulin antibody positivity was 1.0%, 21.8%, 4.7%, 6.6%, and 10.4%, respectively. Logistic regression analysis found that urinary iodine was an independent risk factor for TPOAb positivity (odds ratio = 0.997 [95% confidence interval, 0.995-0.999]; p < 0.001). Conclusions: Compared with individuals living in the plains of China, Tibetan adults have a higher rate of ID. UIC was an independent risk factor for TPOAb positivity. This public health issue should be further investigated.

Trigonelline reduced diabetic nephropathy and insulin resistance in type 2 diabetic rats through peroxisome proliferator-activated receptor-γ.

Trigonelline has been reported to serve an important role in cell cycle control, oxidative and ultraviolet stress and DNA methylation. In the present study, the effects of trigonelline were examined on type-2 diabetes mellitus (T2DM)-induced renal dysfunction, and its possible mechanism was investigated. Sprague-Dawley rats were fed with high-fat diet (HFD) for 4 weeks and intraperitoneally injected with 35 mg/kg of streptozotocin for 4 weeks. As a result, trigonelline increased body weight, inhibited the kidney weight/body weight ratio and blood glucose levels, and reduced the levels of blood urea nitrogen, creatinine and albumin in type 2 diabetic rats. In addition, trigonelline also reduced inflammation, oxidative stress and kidney cell apoptosis in T2DM rats. In terms of the molecular mechanisms involved, trigonelline induced the protein expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppressed glucose transporter 4 but suppressed the protein expression of tumor necrosis factor-α and leptin in T2DM rats. The present results demonstrated that trigonelline reduced diabetic nephropathy and insulin resistance in T2DM rats through PPAR-γ.

SRD005825 Acts as a Pharmacologic Chaperone of Opsin and Promotes Survival of Photoreceptors in an Animal Model of Autosomal Dominant Retinitis Pigmentosa.

PURPOSE: Mutations in RHO, the gene for a rhodopsin, are a leading cause of autosomal dominant retinitis pigmentosa. The objective of this study was to determine if a synthetic retinal analogue (SRD005825) serves as a pharmacologic chaperone to promote appropriate membrane trafficking of a mutant version of human rhodopsin. METHODS: A tetracycline-inducible cell line was used to produce human wild-type and T17M opsin. A cell-free assay was used to study the impact of SRD005825 on binding of 9-cis-retinal to wild-type opsin. A cell-based assay was used to measure the effect of SRD005825 on the generation of rhodopsin by spectroscopy and Western blot and the transport of rhodopsin to the cell membrane by confocal microscopy. Mice bearing T17M RHO were treated with daily oral doses of SRD005825, and retinal degeneration was measured by spectral-domain optical coherence tomography and, at the conclusion of the experiment, by electroretinography and morphometry. RESULTS: SRD005825 competed with 9-cis-retinal for binding to wild-type opsin but promoted the formation of rhodopsin in HEK293 cells and the trafficking of T17M rhodopsin to the plasma membrane of these cells. T17M transgenic mice exhibited rapid retinal degeneration, but thinning of the outer nuclear layer representative of photoreceptor cell bodies was delayed by treatment with SRD005825. Electroretinography a-wave and b-wave amplitudes were significantly improved by drug treatment. CONCLUSIONS: SRD005825 promoted the reconstitution of mutant rhodopsin and its membrane localization. Because it delayed retinal degeneration in the mouse model, it has potential as a therapeutic for autosomal dominant retinitis pigmentosa. TRANSLATIONAL RELEVANCE: SRD005825 may be useful as a treatment to delay retinal degeneration in retinitis pigmentosa patients with rhodopsin mutations causing misfolding of the protein.

[DNA damage, Bcl-2, Bax expression and ultrastructure change in spermatogenic cell of mice exposed to cadmium].

OBJECTIVE: To study DNA damage, Bcl-2 and Bax expression, and ultrastructure change in spermatogenic cell of mice by cadmium exposure. METHODS: Twenty-four male mice were divided into 4 groups: 3 groups treated with cadmium chloride of 1, 5, 10 micromol x kg(-1) x d(-1) i.p. respectively for 5 days, and one normal saline control group. The DNA damage of spermatogenic cell by single-cell gel electrophoresis technology was detected. The expression positive rate of Bcl-2, Bax protein in spermatogenic cell by the immunohistochemical method was assayed, and the ultrastructural change of spermatogenic cell by the transmission electron microscope was observed. RESULTS: DNA damage rates of of spermatogenic cell in 1, 5, 10 micromol/kg cadmium chloride groups were higher than that of normal group (P < 0.001). Bcl-2 protein expression positive rates were lower than that of normal group (P < 0.001). Bax protein positive expression rate in 5 micromol/kg group was higher than those in normal group, and 1, 10 micromol/kg groups. The ultrastructure of karyotis, karyotheca, mitochondria, endoplasmic reticulum in three treated groups had different degree of damage and the degree of ultrastructural change was increasing with rising concentration of cadmium. CONCLUSION: Cadmium exposure will cause the DNA break, Bcl-2 and Bax protein abnormal expression and ultrastructural change in spermatogenic cell.

Affects of Anxiety and Depression on Health-Related Quality of Life among Patients with Benign Breast Lumps Diagnosed via Ultrasonography in China.

There is a high incidence of benign breast lumps among women, and these lumps may lead to physical and psychological problems. This study aims to evaluate anxiety and depressive symptoms among patients with benign breast lumps diagnosed via ultrasonography and investigate their impacts on health-related quality of life (HRQOL). A cross-sectional survey was conducted in Shenyang, China, from January to November 2013. Data were collected with self-administered questionnaires, including the Zung Self-Rating Anxiety Scale (SAS), the Center for Epidemiologic Studies Depression Scale (CES-D), and the 36-item Short-Form Health Survey (SF-36), together with demographic characteristics, from patients of the Department of Breast Surgery of the First Affiliated Hospital of China Medical University. Hierarchical multiple regression analysis (HMR) was performed to explore the effects of anxiety and depression on HRQOL. The overall prevalences of anxiety (SAS score ≥ 40) and depression (CES-D scores ≥ 16) were 40.2% and 62.0%, respectively, and 37.5% of the participants had both of these psychological symptoms. The means and standard deviations of PCS and MCS were 75.42 (15.22) and 68.70 (17.71), respectively. Anxiety and depressive symptoms were significantly negatively associated with the HRQOL of patients with benign breast lumps diagnosed via ultrasonography. Women with benign breast lumps diagnosed via ultrasonography in China experienced relatively high levels of anxiety and depressive symptoms. Anxiety and depressive symptoms had significant negative impacts on both the mental and physical quality of life (QOL) of women with benign breast lumps. Beyond the necessary clinical treatment procedures, psychological guidance and detailed explanations of the disease should be offered to alleviate the anxiety and depressive symptoms and enhance the HRQOL of patients with benign breast lumps.