Protein Tyrosine Phosphatase SHP2 in Macrophages Acts as an Antiatherosclerotic Regulator in Mice.

BACKGROUND: Macrophages have versatile roles in atherosclerosis. SHP2 (Src homology 2 containing protein tyrosine phosphatase 2) has been demonstrated to play a critical role in regulating macrophage activation. However, the mechanism of SHP2 regulation of macrophage function in an atherosclerotic microenvironment remains unknown. METHODS: APOE (apolipoprotein E) or LDLR (low-density lipoprotein receptor) null mice treated with SHP099 were fed a Western diet for 8 weeks, while Shp2MKO:ApoE-/- or Shp2MKO:Ldlr-/- mice and exo-AAV8-SHP2E76K/ApoE-/- mice were fed a Western diet for 12 weeks. In vitro, levels of proinflammatory factors and phagocytic function were then studied in mouse peritoneal macrophages. RNA sequencing was used to identify PPARγ (peroxisome proliferative activated receptor γ) as the key downstream molecule. A PPARγ agonist was used to rescue the phenotypes observed in SHP2-deleted mice. RESULTS: Pharmacological inhibition and selective deletion in macrophages of SHP2 aggravated atherosclerosis in APOE and LDLR null mice with increased plaque macrophages and apoptotic cells. In vitro, SHP2 deficiency in APOE and LDLR null macrophages enhanced proinflammatory polarization and its efferocytosis was dramatically impaired. Conversely, the expression of gain-of-function mutation of SHP2 in mouse macrophages reduced atherosclerosis. The SHP2 agonist lovastatin repressesed macrophage inflammatory activation and enhanced efferocytosis. Mechanistically, RNA sequencing analysis identified PPARγ as a key downstream transcription factor. PPARγ was decreased in macrophages upon SHP2 deletion and inhibition. Importantly, PPARγ agonist decreased atherosclerosis in SHP2 knockout mice, restored efferocytotic defects, and reduced inflammatory activation in SHP2 deleted macrophages. PPARγ was decreased by the ubiquitin-mediated degradation upon SHP2 inhibition or deletion. Finally, we found that SHP2 was downregulated in atherosclerotic vessels. CONCLUSIONS: Overall, SHP2 in macrophages was found to act as an antiatherosclerotic regulator by stabilizing PPARγ in APOE/LDLR null mice.

Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

Reactive Matrices for MALDI-MS of Cholesterol.

Cholesterol is a critical molecule whose dysregulation in certain brain regions is related to multiple neurological disorders. It is of pathological importance to map the distribution of cholesterol in brain. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been widely used in the molecular imaging of metabolites at a high spatial resolution. However, it is challenging to analyze cholesterol by MALDI-MS due to its difficulty in ionization. Herein, we present for the first time a type of reactive matrix for MALDI-MS of cholesterol. Methylpyridinium carboxaldehydes react with cholesterol and other hydroxyl-containing sterols, which greatly enhanced both desorption and ionization and improved the limits of detection to the low µg/mL range. Compared with previous methods, our reactive matrix requires only one step of chemical derivatization and avoids time-consuming enzymatic reaction, which simplified the sample pretreatment. The reactive matrix was successfully used in mapping the distribution of cholesterol in brain tissue sections using MALDI-MS imaging. In summary, this work has provided a sensitive and simple method for the MALDI-MS analysis of cholesterol, has proposed a novel solution to visualize the distribution of sterol metabolites, and has great potential for applications in neurological and pathological studies.

Identification of Key Biomarkers and Candidate Molecules in Non-Small-Cell Lung Cancer by Integrated Bioinformatics Analysis.

Background: Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods: From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal, String and Cytoscape, and Timer tools. Results: We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis (P < 0.05). We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis (P < 0.05). On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients (P < 0.05). Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions: The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.

Deep learning-assisted diagnosis of parotid gland tumors by using contrast-enhanced CT imaging.

OBJECTIVES: Imaging interpretation of the benignancy or malignancy of parotid gland tumors (PGTs) is a critical consideration prior to surgery in view of therapeutic and prognostic values of such discrimination. This study investigates the application of a deep learning-based method for preoperative stratification of PGTs. MATERIALS AND METHODS: Using the 3D DenseNet-121 architecture and a dataset consisting of 117 volumetric arterial-phase contrast-enhanced CT scans, we developed a binary classifier for PGT distinction and tested it. We compared the discriminative performance of the model on the test set to that of 12 junior and 12 senior head and neck clinicians. Besides, potential clinical utility of the model was evaluated by measuring changes in unassisted and model-assisted performance of junior clinicians. RESULTS: The model finally reached the sensitivity, specificity, PPV, NPV, F1-score of 0.955 (95% CI 0.751-0.998), 0.667 (95% CI 0.241-0.940), 0.913 (95% CI 0.705-0.985), 0.800 (95% CI 0.299-0.989) and 0.933, respectively, comparable to that of practicing clinicians. Furthermore, there were statistically significant increases in junior clinicians' specificity, PPV, NPV and F1-score in differentiating benign from malignant PGTs when unassisted and model-assisted performance of junior clinicians were compared. CONCLUSION: Our results provide evidence that deep learning-based method may offer assistance for PGT's binary distinction.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Regioselective Synthesis of 5-Trifluoromethylpyrazoles by [3 + 2] Cycloaddition of Nitrile Imines and 2-Bromo-3,3,3-trifluoropropene.

A general and practical method for the synthesis of 5-trifluoromethylpyrazoles is reported that occurs by the coupling of hydrazonyl chlorides with environmentally friendly and large-tonnage industrial feedstock 2-bromo-3,3,3-trifluoropropene (BTP). This exclusively regioselective [3 + 2] cycloaddition of nitrile imines and with BTP is catalyst-free and operationally simple and features mild conditions, high yields, gram-scalable, a broad substrate scope, and valuable functional group tolerance. Significantly, our method has been applied for the synthesis of the key intermediate of an active agonist of sphingosine 1-phosphate receptor.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Immunometabolism-modulation and immunotoxicity evaluation of perfluorooctanoic acid in macrophage.

Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated chemicals in industry. Wide concerns of PFOA toxicity are increased in recent years. However, report on immunotoxicity of PFOA was quite limited. This study aimed to investigate the immunotoxicity of PFOA exposure on macrophage RAW264.7. We assessed the effects of PFOA exposure on macrophage cell viability, cell apoptosis and cellular ROS level, and detected prominent cytokines release by RAW264.7. The results indicated that the cell viability of macrophage RAW264.7 was decreased by PFOA in dose- and time-dependent manners. Specifically, the exposure of 200 µM PFOA significantly increased apoptosis and ROS generation in macrophage, and thus caused cell damage. The ELISA results displayed that 100 µM PFOA exposure induced macrophage activation and enhanced cytokines secretion, including TNF-α, IL-1, IL-6, and IL-12. We also conducted nontargeted metabolomics based on LC-MS/MS and unveiled the perturbed metabolic pathways in macrophages induced by sublethal doses of PFOA (10 µM and 100 µM). Remarkably, global metabolomics results displayed that 10 µM PFOA exposure affected glutamine related pathways and the exposure at 100 µM conspicuously changed glutathione and fatty acid oxidation metabolism. These findings showed that 10 µM PFOA exposure could impel metabolic reprogramming of macrophage to trigger inflammatory response, although such dose displayed no obvious effect on cell viability, cellular ROS or apoptosis events of macrophage RAW264.7.

Fluorohalogenation of gem-Difluoroalkenes: Synthesis and Applications of α-Trifluoromethyl Halides.

A novel strategy for 1,2-dihalogenation of alkenes is reported that occurs through a sequential nucleophilic halide addition and electrophilic halogenation. By trapping the in situ generated unstable α-trifluoromethyl carbanion intermediates derived from the nucleophilic fluoride addition to electron-poor gem-difluoroalkenes, this fluorohalogenation of gem-difluoroalkenes with electrophilic haloalkynes affords various useful α-trifluoromethyl halides in high yields. A pesticidal active compound and various attractive trifluromethylated molecules could be smoothly synthesized from these obtained α-trifluoromethyl halides.

Long non-coding RNA ZEB2-AS1 promotes the proliferation, metastasis and epithelial mesenchymal transition in triple-negative breast cancer by epigenetically activating ZEB2.

The triple-negative breast cancer is the most malignant type of breast cancer. Its pathogenesis and prognosis remain poor despite the significant advances in breast cancer diagnosis and therapy. Meanwhile, long noncoding RNAs (LncRNAs) play a pivotal role in the progression of malignant tumors. In this study, we found that LncRNA-ZEB2-AS1 was dramatically up-regulated in our breast cancer specimens and cells (MDA231), especially in metastatic tumor specimens and highly invasive cells, and high lncRNA-ZEB2-AS1 expression is associated with clinicopathologic features and short survival of breast cancer patients. LncRNA-ZEB2-AS1 promotes the proliferation and metastasis of MDA231 cells in SCID mice. Thus, it is regarded as an oncogene in triple-negative breast cancer. It is mainly endo-nuclear and situated near ZEB2, positively regulating ZEB2 expression and activating the epithelial mesenchymal transition via the PI3K/Akt/GSK3ß/Zeb2 signaling pathway. Meanwhile, EGF-induced F-actin polymerization in MDA231 cells can be suppressed by reducing lncRNA-ZEB2-AS1 expression. The migration and invasion of triple-negative breast cancer can be altered through cytoskeleton rearrangement. In summary, we demonstrated that lncRNA-ZEB2-AS1 is an important factor affecting the development of triple-negative breast cancer and thus a potential oncogene target.

Exposure Assessment of Bisphenols in Chinese Women during Pregnancy: A Longitudinal Study.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used in manufacturing consumer products to replace the use of bisphenol A (BPA), but exposure data are limited, particularly among pregnant women. Here, we measured BPA, BPS, and BPF levels in urine samples, collected from 941 pregnant women over three trimesters. We examined the correlations, coexposure patterns, variability, and predictors of bisphenols using Spearman's correlation coefficient, percentile analysis, intraclass correlation coefficient, and linear mixed models, respectively. We assessed health risks using average concentrations of bisphenols over three trimesters. The three bisphenols were detected in more than 50% of samples, among which BPA was the predominant one. Cashiers, office workers, teachers, and salespersons had elevated urinary BPS concentrations, while healthcare workers had relatively higher BPA concentrations. About 15 participants had potential health risks induced by exposure to bisphenol mixtures. These findings indicate that exposure to multiple bisphenols at low levels is common over three trimesters. Multiple measurements of urinary BPA and BPS concentrations are needed for more accurate evaluation of the exposure levels during pregnancy, while urinary BPF concentrations during pregnancy are moderately reliable. Occupational exposure should be taken into consideration in future demographic studies.

The association between short-term exposure to ambient air pollution and the incidence of mumps in Wuhan, China: A time-series study.

BACKGROUND: Previous studies have estimated the association between meteorological factors and mumps outbreaks without assessing the influence of air pollution. In this research, we explored the effects of short-term exposure to air pollution on the incidence of mumps. METHODS: Our time-series analysis was conducted using data collected in Wuhan, China from 2015 to 2017. Daily number of mumps cases was obtained from Disease Reporting System in Hubei Provincial Center for Disease Control and Prevention. Data on air pollution was obtained from 10 national air quality monitoring stations, including nitrogen dioxide (NO2), sulfur dioxide (SO2), ground-level ozone (O3), particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10), and particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5). Daily meteorological data including temperature and relative humidity were obtained from Hubei Meteorological Bureau. We performed a Poisson regression in generalized additive models (GAM) to explore the association between the incidence of mumps and exposure to air pollution. RESULTS: We observed that the effects of air pollutants were statistically significant mainly in two periods, lag 0 to lag 5 and lag 20 to lag 25, with the strongest effects appearing at lag 2 and lag 23. The cumulative effects were stronger than single-day lag effects. The stratified analysis showed the effect of pollutants during the hot season was stronger than that during the cold season, especially for NO2 and SO2. CONCLUSIONS: We found that exposure to NO2 and SO2 was significantly associated with higher risk of developing mumps. Our findings could help deepen the understanding of how air pollution exposure affects the incidence of mumps.

Copper-Catalyzed Unstrained C-C Single Bond Cleavage of Acyclic Oxime Acetates Using Air: An Internal Oxidant-Triggered Strategy toward Nitriles and Ketones.

A copper-catalyzed aerobic oxidative C-C single bond cleavage of acyclic unstrained oxime acetates is reported, providing various aryl nitriles and ketones in good yields. Mechanistic studies indicate a radical procedure is involved in this transformation, and the oxygen atom in the ketone products is originated from O2 in the air. Oxime acetates as an internal oxidant have been proved to be an initiator, which may promote the discovery of novel protocol for C-C bond cleavage and dioxygen activation.

Intermolecular C(sp3 )-H Amination Promoted by Internal Oxidants: Synthesis of Trifluoroacetylated Hydrazones.

An intermolecular C(sp3 )-H amination reaction is reported that is promoted by internal oxidants and occurs via a C=N bond formation step. This intermolecular C(sp3 )-H amination reaction of trifluoromethyl ketones and aryldiazonium tetrafluoroborates affords various valuable trifluoroacetylated hydrazones in high yields with excellent E/Z selectivities. The salient features of this reaction type is that it is free of metal, catalyst, directing groups, and azides, and that it can be carried out under mild conditions, is operationally simple and efficient, gram-scalable, and it tolerates various functional groups. Remarkably, an ectoparasites-controlling agent was smoothly synthesized on a gram scale using our method. Aryldiazonium tetrafluoroborates served as the aminating reagents as well as an internal oxidant.

Comprehensive Analysis of Acylcarnitine Species in db/db Mouse Using a Novel Method of High-Resolution Parallel Reaction Monitoring Reveals Widespread Metabolic Dysfunction Induced by Diabetes.

Acylcarnitines are exerting a variety of biological functions depending on the differences in lengths, saturation levels, and conjugation groups, which to a great extent contribute to the challenges of acylcarnitines quantifications due to various kinds of isomers. Here, we describe a novel method by using high-resolution parallel reaction monitoring (PRM) liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both reversed-phase and normal-phase column were used in order to get accurate, reliable, widespread quantification of acylcarnitines, and without tedious sample preparation procedure. The method provided the most comprehensive acylcarnitine profile with high-resolution MS and MS/MS confirmation to date. A total of 117 acylcarnitines were detected from plasma and urine samples. The application of targeted profiling of acylcarnitines in db/m+ control and db/db diabetic mice indicated incomplete amino acid and fatty acid oxidation on diabetic mice. Interestingly, the reduction of medium odd-numbered chain acylcarnitines in urine samples was first observed between db/m+ and db/db mice. The high-resolution PRM method makes it possible to monitor the widespread metabolic changes of the acylcarnitines in response to stimuli. Besides, the accurate MS and MS/MS spectra data of the 117 acylcarnitines could be used as mass spectrometric resources for the identification of acylcarnitines.

Investigation on fragmentation pathways of bisphenols by using electrospray ionization Orbitrap mass spectrometry.

RATIONALE: Bisphenols, such as bisphenol A (BPA) and bisphenol S (BPS), are widely used in industrial products, although they have been demonstrated to be environmental contaminants with toxicity. However, few studies on the mass spectrometric fragmentation pathway of these compounds have been reported using high-resolution mass spectrometry (HRMS). METHODS: The MS/MS fragmentations of nine bisphenols, together with several corresponding isotope-labeled compounds, were studied by Orbitrap MS using electrospray ionization (ESI) in negative ion mode and higher energy collisional-dissociation (HCD). The [M - H](-) ions of the compounds formed by ESI were selected as the precursor ions for MS/MS. The accurate m/z values for product ions were acquired to deduce the elemental compositions and fragmentation pathways. RESULTS: The elemental compositions of the ions were calculated from the accurate mass data. Common MS/MS product ions and characteristic neutral losses were summarized. Six bisphenols formed the common product ion at m/z 93 (C6 H5 O). The [M - H](-) ions of five bisphenols were found to lose a phenol group (C6 H5 OH). Four bisphenols formed the [M - H - CH4 ](-) ion. The proposed fragmentation pathways of representative compounds of BPA and BPS were verified from the analysis of isotope-labeled compounds. CONCLUSIONS: The MS/MS fragmentation pathways of nine bisphenols were, for the first time, systematically investigated with HRMS. The obtained data could be valuable for the identification of a variety of bisphenols in environmental and biological samples.

Association of alpha-ADD1 Gene and Hypertension Risk: A Meta-Analysis.

BACKGROUND: Results regarding the association between a-adducin (ADD1) gene and essential hypertension (EH) risk remain inconsistent. Therefore, we performed this meta-analysis to investigate this association. MATERIAL AND METHODS: We comprehensively searched published literature from PubMed and Embase. All studies analyzing the association between ADD1 Gly460Trp polymorphism and EH risk were included. Fixed- or random-effects model was used to calculate pooled odds ratio (OR) with 95% confidence interval (CI). RESULTS: Data synthesis showed an increased risk of EH in T allele variant carriers with Asian descent, for GG vs. TT (OR=0.750, 95%CI: 0.585-0.960; P=0.022), recessive model (OR=1.196, 95%CI: 1.009-1.418; P=0.039), dominant model (OR=0.826, 95%CI: 0.693-0.985; P=0.033), and allelic model (OR=0.859, 95%CI: 0.756-0.964; P=0.01), respectively. However, no statistical differences were observed in Blacks and Caucasians. CONCLUSIONS: The findings showed the association of the T allele in ADD1 gene with EH susceptibility in Asians. However, well-designed studies involving gene-gene and gene-environment interactions should be considered in future.

[Risk factors associated with chronic obstructive pulmonary disease: a comparison between urban and rural populations in Chengdu].

OBJECTIVE: To determine risk factors associated with the prevalence of chronic obstructive pulmonary disease (COPD) in urban and rural populations in Chengdu. METHODS: A multistage random cluster sampling method was adopted to select participants from four communities in Chengdu. All residents aged 40-70 yr. were eligible to participate in this study, which involved a questionnaire survey, physical examination and portable spirometry. Those with airflow limitations were also given post-bronchodilator testing 15 min after inhalation of a dose of 200 microg salbutamol. We defined a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of less than 70% as COPD. Logistic regression models were performed to identify risk factors of COPD. RESULTS: Of a total of 1931 eligible participants, 1579 (81.77%) completed the questionnaire and spirometry. About 8.35% were identified with COPD: 7.69% in urban vs. 12.37% in rural (P<0.05). The prevalence of COPD increased with age (P<0.05) in the male and total populations. Rural COPD patients had a higher level of smoking rate and use of coal as fuel for cooking than their urban counterparts (P<0.05). But rural COPD patients had a lower level of BMI, waist circumference, literacy, and average household income per capita than their urban counterparts (P<0.05). The multivariate analysis showed that tobacco smoking index (pack-year), education, age and BMI were predictors of COPD for male patients; whereas, coal fuel usage, income and BMI were predictors of COPD for female patients. CONCLUSION: COPD prevalence is higher in rural areas than in urban Chengdu. Major risk factors of COPD include smoking, coal fuels and BMI.