Adrenomedullin, transcriptionally regulated by vitamin D receptors, alleviates atherosclerosis in mice through suppressing AMPK-mediated endothelial ferroptosis.

PURPOSE: Vitamin D receptors (VDR) play important roles in cardiovascular, immune, metabolic and other functions. Activation of VDR may help improve endothelial dysfunction, atherosclerosis, vascular calcification, and cardiac hypertrophy. However, the specific target genes and mechanisms of VDR in improving Human Umbilical Vein Endothelial Cell (HUVEC) functions remain unclear. This study aims to investigate the function and mechanism of VDR in HUVECs. METHODS: Endothelial dysfunction cell model was constructed by oxidized low-density lipoprotein (ox-LDL). An animal model of atherosclerosis was established in male homozygous Apoe-/- mice (6 weeks) on a high fat diet for 6 weeks. The relationship between VDR and adrenomedullin (ADM) was studied by bioinformatics analysis, ChIP, and luciferase reporter gene analysis. Endothelial cell function was evaluated by Transwell migration and Tube Formation tests. Ferroptosis was detected by measuring intracellular iron content, levels of oxidative stress markers, and ferroptosis related proteins. RESULTS: Overexpression of VDR in HUVECs inhibits ox-LDL-induced endothelial dysfunction and ferroptosis. VDR binds to the ADM promoter sequence and regulates the transcription of ADM. Inhibition of ADM promotes ox-LDL-induced endothelial dysfunction and ferroptosis. ADM regulates ox-LDL-induced endothelial dysfunction and ferroptosis through the AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice inhibited lipid deposition and plaque area in atherosclerotic mice. CONCLUSION: VDR inhibits ox-LDL-induced endothelial dysfunction and ferroptosis by regulating ADM transcription and acting on AMPK signaling pathway. Overexpression of VDR in Apoe-/- mice reduced lipid deposition and plaque area in the thoracic aorta of atherosclerotic mice.

Spatio-temporal evolution patterns of influenza incidence and its nonlinear spatial correlation with environmental pollutants in China.

BACKGROUND: Currently, the influenza epidemic in China is at a high level and mixed with other respiratory diseases. Current studies focus on regional influenza and the impact of environmental pollutants on time series, and lack of overall studies on the national influenza epidemic and the nonlinear correlation between environmental pollutants and influenza. The unclear spatial and temporal evolution patterns of influenza as well as the unclear correlation effect between environmental pollutants and influenza epidemic have greatly hindered the prevention and treatment of influenza epidemic by relevant departments, resulting in unnecessary economic and human losses. METHOD: This study used Chinese influenza incidence data for 2007-2017 released by the China CDC and air pollutant site monitoring data. Seasonal as well as inter monthly differences in influenza incidence across 31 provinces of China have been clarified through time series. Space-Time Cube model (STC) was used to investigate the spatio-temporal evolution of influenza incidence in 315 Chinese cities during 2007-2017. Then, based on the spatial heterogeneity of influenza incidence in China, Generalized additive model (GAM) was used to identify the correlation effect of environmental pollutants (PM2.5, PM10, CO, SO2, NO2, O3) and influenza incidence. RESULT: The influenza incidence in China had obvious seasonal changes, with frequent outbreaks in winter and spring. The influenza incidence decreased significantly after March, with only sporadic outbreaks occurring in some areas. In the past 11 years, the influenza epidemic had gradually worsened, and the clustering of influenza had gradually expanded, which had become a serious public health problem. The correlation between environmental pollutants and influenza incidence was nonlinear. Generally, PM2.5, CO and NO2 were positively correlated at high concentrations, while PM10 and SO2 were negatively correlated. O3 was not strongly correlated with the influenza incidence. CONCLUSION: The study found that the influenza epidemic in China was in a rapidly rising stage, and several regions had a multi-year outbreak trend and the hot spots continue to expand outward. The association between environmental pollutants and influenza incidence was nonlinear and spatially heterogeneous. Relevant departments should improve the monitoring of influenza epidemic, optimize the allocation of resources, reduce environmental pollution, and strengthen vaccination to effectively prevent the aggravation and spread of influenza epidemic in the high incidence season and areas.

Spatial distribution of anti-mullerian hormone in females of childbearing age in China under the influence of geographical environmental factors.

The Anti-mullerian hormone (AMH) reference value is an important indicator of ovarian function. The main targets of this were to screen the geographical environmental factors that may influence the distribution of AMH reference values in Chinese females of childbearing age, and to further explore the geographical distribution differences of AMH reference values. We gathered the AMH data of 28,402 healthy Chinese females from 62 cities in China for this study in order to conduct a spearman regression analysis to determine the relationship between the AMH and 30 geography factors. The AMH reference value in different regions was forecasted by using a ridge regression model. The magnitude of influence from the geographical factor on different regions was analysed by geographically weighted regression. Ultimately, We were able to figure out the geographic distribution risk prediction of AMH reference values by utilizing the disjunctive Kriging method. The AMH reference value was significantly correlated with the 16 secondary indexes. The geographical distribution of AMH showed a trend of being higher in Qinghai-Tibet and Southern regions, and lower in the Northwest and Northern regions. This study lays the foundation for future investigations into the mechanism of different influencing factors on the reference value of AMH. It is suggested that such regional variations in AMH reference values be taken into account while diagnosing and treating individuals with reproductive medicine.

Associations of environmental factors with total cholesterol level of middle-aged and elderly people in China.

BACKGROUND: Dyslipidemia is a key factor causing cardio cerebrovascular diseases, and the total cholesterol (TC) is an important lipid indicator among them. Studies have shown that environmental factors have a strong association with TC levels. Previous studies only focused on the seasonal variation of TC level and the short-term effects of some environmental factors on TC level over time, and few studies explored the geographical distribution of TC level and quantified the impact of environmental factors in space. METHODS: Based on blood test data which was from China Health and Retirement Longitudinal Study (Charls) database, this study selected the TC level test data of middle-aged and elderly people in China in 2011 and 2015, and collected data from 665 meteorological stations and 1496 air pollutant monitoring stations in China. After pretreatment, the spatial distribution map of TC level was prepared and the regional statistics were made. GeoDetector and geographically weighted regression (GWR) were used to measure the relationship between environmental factors and TC level. RESULTS: The TC level of middle-aged and elderly in China was higher in females than in males, and higher in urban areas than in rural areas, showing a clustered distribution. The high values were mainly in South China, Southwest China and North China. Temperature, humidity, PM10 and PM2.5 were significant environmental factors affecting TC level of middle-aged and elderly people. The impact of pollutants was more severe in northern China, and TC level in southern China was mainly affected by meteorological factors. CONCLUSIONS: There were gender and urban-rural differences in TC levels among the middle-aged and elderly population in China, showing aggregation in geographical distribution. Meteorological factors and air pollutants may be very important control factors, and their influencing mechanism needs further study.

Urotensin II activates the ferroptosis pathway through circ0004372/miR-124/SERTAD4 to promote the activation of vascular adventitial fibroblasts.

Both vascular adventitial fibroblasts (VAFs) and urotensin II (UII) play important roles in vascular remodeling diseases, but the mechanism of UII in VAFs is still unclear. UII inhibited miR-124 expression through up-regulating circ0004372 expression, thereby promoting SERTAD4 expression. UII significantly promoted the generation of ROS, MDA and 4-HNE, reduced the activities of SOD, GST and GR, increased Fe2+ concentration and inhibited GPX4 expression through circ0004372/miR-124/SERTAD4. Both UII and ferroptosis inducer Erastin significantly promoted the expression of α-SMA, Collagen I and TGF-ß1 in VAFs, but circ0004372 siRNA, miR-124 mimics, SERTAD4 siRNA or Ferrostatin-1 significantly inhibited the effect of UII and Erastin on cell activation. When co-transfected with circ0004372 siRNA and miR-124 inhibitors or miR-124 mimics and SERTAD4 overexpression vector, UII still significantly increased the expression of α-SMA, Collagen I and TGF-ß1. After transfection with circ0004372 overexpression vector, miR-124 inhibitors or SERTAD4 overexpression vector and then treating with UII and Ferrostatin-1, the expression of α-SMA, Collagen I and TGF-ß1 was still significant; when the circ0004372 overexpression vector and miR-124 mimics or miR-124 inhibitors and SERTAD4 siRNA were co-transfected and then UII and Ferrostatin-1 were added, the expression of α-SMA, Collagen I and TGF-ß1 was not significantly increased. Therefore, these results indicate that UII promotes the activation of VAFs through the circ0004372/miR-124/SERTAD4/ferroptosis pathway.

Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression.

Recent research indicates that lactate promotes the switching of vascular smooth muscle cells (VSMCs) to a synthetic phenotype, which has been implicated in various vascular diseases. This study aimed to investigate the effects of lactate on the VSMC phenotype switch and the underlying mechanism. The CCK-8 method was used to assess cell viability. The microRNAs and mRNAs levels were evaluated using quantitative PCR. Targets of microRNA were predicted using online tools and confirmed using a luciferase reporter assay. We found that lactate promoted the switch of VSMCs to a synthetic phenotype, as evidenced by an increase in VSMC proliferation, mitochondrial activity, migration, and synthesis but a decrease in VSMC apoptosis. Lactate inhibited miR-23b expression in VSMCs, and miR-23b inhibited VSMC's switch to the synthetic phenotype. Lactate modulated the VSMC phenotype through downregulation of miR-23b expression, suggesting that overexpression of miR-23b using a miR-23b mimic attenuated the effects of lactate on VSMC phenotype modulation. Moreover, we discovered that SMAD family member 3 (SMAD3) was the target of miR-23b in regulating VSMC phenotype. Further findings suggested that lactate promotes VSMC switch to synthetic phenotype by targeting SMAD3 and downregulating miR-23b. These findings suggest that correcting the dysregulation of miR-23b/SMAD3 or lactate metabolism is a potential treatment for vascular diseases.

LncRNA-MIAT regulates fibrosis in hypertrophic cardiomyopathy (HCM) by mediating the expression of miR-29a-3p.

AIM: This study aimed to investigate the molecular mechanism underlying the fibrosis in hypertrophic cardiomyopathy (HCM). METHOD: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of potentially relevant microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in patients with HCM suffering from fibrosis and patients with HCM free of fibrosis. In addition, the regulatory relationship between lncRNAs and miR-29a was studied using a luciferase assay. Subsequently, area under the receiver-operating characteristics (ROC) curve (AUC) analysis was conducted to predict the diagnostic value of myocardial infarction-associated transcript (MIAT), miR-29a, H19, and MEG3 in patients with HCM. Finally, the predicted regulatory relationship betwe en miR-29a and MIAT was validated by transfecting cells with different plasmids. RESULT: miR-29a and MIAT were differently expressed between the fibrosis (+) HCM group and the fibrosis (-) HCM group, thus establishing a negative relationship between the expression of these two genes. In addition, both MIAT and miR-29a showed the ability to accurately predict the prognosis in patients with HCM. Furthermore, the luciferase activity of wild-type MIAT was evidently suppressed in cells transfected with miR-29a mimics, suggesting that the expression of miR-29a was apparently downregulated in the presence of MIAT. CONCLUSION: The results obtained in this study collectively indicated that the MIAT might be associated with the development of fibrosis (+) HCM via negatively regulating the expression of miR-29a.

Tanshinone IIA attenuates high glucose induced human VSMC proliferation and migration through miR-21-5p-mediated tropomyosin 1 downregulation.

The proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the development and progression of diabetes-related vascular complications. Recently, microRNAs (miRNAs) have been suggested to be involved in the pathogenesis of vascular diseases. This study was designed to investigate the influences of tanshinone IIA, an active compound extracted from Chinese herb Salvia miltiorrhiza, on the proliferation and migration of human aortic VSMCs (HASMCs). cultured in a high glucose medium and the underlying mechanisms related miRNAs. Using a miRNA microarray method, we profiled the miRNA expression signature in human aortic VSMCs (HASMCs) exposed to normal glucose, high glucose with and without Tanshinone IIA. Cell proliferation was measured with 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Cell migration was evaluated using transwell migration assay and wound scratch assay. Western blot was used to examine the expression of tropomyosin 1 (TPM1) and miRNA level was quantified by real-time PCR. The results showed that several miRNAs that were highly expressed in the high glucose group were significantly decreased in the high glucose with Tanshinone IIA group compared with the normal glucose group (P < 0.05). Among these miRNAs, miR-21-5p was significantly upregulated in the high glucose group and downregulated after Tanshinone IIA treatment (P < 0.05). The depletion of miR-21-5p in HASMCs resulted in decreased cell proliferation and migration (P < 0.05). Moreover, we found that Tanshinone IIA inhibited proliferation and migration partly through miR-21-5p-mediated TPM1 downregulation (P < 0.05). In conclusion, the present study demonstrates that Tanshinone IIA is able to protect HASMCs from high glucose-induced proliferation and migration through regulating expression of miRNAs.

Circulating MiR-146a May be a Potential Biomarker of Coronary Heart Disease in Patients with Subclinical Hypothyroidism.

BACKGROUND/AIMS: Subclinical hypothyroidism (SCH) plays a crucial role in the development and progression of coronary heart disease (CHD). However, any associated changes in the circulating microRNAs (miRNAs) levels and slightly elevated thyroid stimulating hormone (TSH) levels in CHD patients are unknown. miR-146a is a well known miRNA associated with inflammatory autoimmune diseases. Here, we evaluated miR-146a expression in patients, with the goal of re-evaluating the effect of SCH on CHD. METHODS: A total of 192 study subjects who underwent coronary angiography for either suspected or confirmed CHD were enrolled in 3 groups: CHD with SCH, CHD alone, and healthy controls. The circulating levels of miR-146a were quantified using qRT-PCR. RESULTS: Levels of miR-146a were positively correlated with CHD severity, as indicated by the Gensini score (r=0.354). The relative expression of miR-146a in the CHD+SCH, CHD and healthy control groups was 2.223±0.827, 1.588±0.726 and 0.632±0.309, respectively. Plasma TSH levels were positively correlated with miR-146a levels (r=0.321). According to multivariate logistic regression analyses, miR-146a levels were associated with the incidence of CHD in patients with SCH. For diagnosing CHD, the area under the ROC curve (AUC) of miR-146a and TSH was 0.779 and 0.752, respectively. When the TSH and miR-146a levels were combined to form a composite panel, the AUC of the panel was 0.858. CONCLUSION: Plasma miR-146a levels correlated with the severity of coronary atherosclerosis and increased with TSH slightly elevated in patients with CHD. Thus, miR-146a may have good predictive value for CHD among individuals with elevated TSH levels.

Circ-SATB2 upregulates STIM1 expression and regulates vascular smooth muscle cell proliferation and differentiation through miR-939.

The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved. More and more studies have found that circular RNAs (circRNAs) may play important roles in the development of CHD. Here detection of vascular smooth muscle cells (VSMCs) showed that circ-SATB2 and STIM1 were up-regulated in proliferative VSMCs, while miR-939 were down-regulated. Circ-SATB2 and miR-939 did not affect the expression of each other, but circ-SATB2 could promote while miR-939 inhibited the expression of STIM1 (a target gene of miR-939). Circ-SATB2 overexpression could inhibit the expression of SM22-alpha (SM22α, a marker of contractile VSMCs), while the expression of SM22α was promoted by miR-939. STIM1 could promote cell proliferation and migration, and circ-SATB2 had similar effects, but its linear sequence had no such functions. MiR-939 had the opposite effects, could promote cell apoptosis and inhibit cell proliferation and migration, and siRNAs targeting circ-SATB2 had similar effects. When co-transfected with circ-SATB2 over-expression vector and miR-939 mimics or STIM1 siRNAs, the changes of cell proliferation, apoptosis and migration were not significant. Therefore, circ-SATB2 can regulate VSMC phenotypic differentiation, proliferation, apoptosis and migration by promoting the expression of STIM1. This discovery will provide a theoretical reference for exploring the role of circRNA in VSMCs and the pathogenesis of CHD.

Magnesium Citrate Protects Against Vascular Calcification in an Adenine-induced Chronic Renal Failure Rat Model.

BACKGROUND: Hypomagnesemia was identified as a strong risk factor for cardiovascular disease in patients with chronic renal failure (CRF). However, the effects of magnesium (Mg) on vascular calcification (VC) have not been fully elucidated. Thus, we aim to determine the effects of Mg citrate (MgCit) on VC in CRF rats. METHODS: Rats were divided into 5 groups: group 1 (normal diet), group 2 (normal diet with MgCit), group 3 (the VC model of CRF induced by 0.75% adenine and 0.9% phosphorus diet from day 1 to day 28), group 4 (group 3 treated with low-dose MgCit from day 1 to day 42), and group 5 (same as group 3 except the high-dose MgCit). All rats were killed at day 43 with collection of blood and aortas. Then, serum biochemical parameters, VC-related staining, calcium and P contents, alkaline phosphatase contents and activity, expression of alpha smooth muscle actin, and runt-related transcription factor 2 (RUNX2) in aortas were assessed. RESULTS: Group 3 had extensive VC. The VC degree decreased in groups 4 and 5 in a dose-depended manner with reduced calcium content, P levels, alkaline phosphatase content and activity, and protein levels of RUNX2 and increased protein levels of alpha smooth muscle actin in aortas. CONCLUSIONS: MgCit exerted a protective role in VC in adenine-induced CRF rats; thus, it may be a potential drug for the prevention of VC in patients with CRF.

The Spatial Distribution Characteristics of the Tumor Biomarker Alpha-fetoprotein: A Cross-section Study.

OBJECTIVES: This study aims to explore the spatial characteristics of the alpha-fetoprotein (AFP) reference value in healthy Chinese adults, and its relationship to geographical location. METHODS: A total of 9396 AFP reference values were collected from patients in 96 administrative units. A correlation analysis and support vector machine (SVM) were employed to extract dependent geographical factors and predict the reference values in the entire country, respectively. A geostatistics analysis was developed to reveal the spatial characteristics of the value. RESULTS: Under the long-term influence of geographical environment, AFP reference values show spatial autocorrelation and regional variation. The values are higher in western and northern areas than in eastern and southern areas of China. CONCLUSIONS: The AFP reference values show regional differences, and this difference should be considered in clinical practice.

The effect of geographical indices on left ventricular structure in healthy Han Chinese population.

The left ventricular posterior wall thickness (LVPWT) and interventricular septum thickness (IVST) are generally regarded as the functional parts of the left ventricular (LV) structure. This paper aims to examine the effects of geographical indices on healthy Han adults' LV structural indices and to offer a scientific basis for developing a unified standard for the reference values of adults' LV structural indices in China. Fifteen terrain, climate, and soil indices were examined as geographical explanatory variables. Statistical analysis was performed using correlation analysis. Moreover, a back propagation neural network (BPNN) and a support vector regression (SVR) were applied to developing models to predict the values of two indices. After the prediction models were built, distribution maps were produced. The results show that LV structural indices are characteristically associated with latitude, longitude, altitude, average temperature, average wind velocity, topsoil sand fraction, topsoil silt fraction, topsoil organic carbon, and topsoil sodicity. The model test analyses show the BPNN model possesses better simulative and predictive ability in comparison with the SVR model. The distribution maps of the LV structural indices show that, in China, the values are higher in the west and lower in the east. These results demonstrate that the reference values of the adults' LV structural indices will be different affected by different geographical environment. The reference values of LV structural indices in one region can be calculated by setting up a BPNN, which showed better applicability in this study. The distribution of the reference values of the LV structural indices can be seen clearly on the geographical distribution map.

The effects of chrysophanol on ovalbumin (OVA)-induced chronic lung toxicology by inhibiting Th17 response.

Chrysophanol (CH), extracted from plants of Rheum genus, possesses various pharmacological effects including anti-inflammatory activity. The purpose of the present study was to evaluate the protective effects and the underlying mechanisms of CH on ovalbumin (OVA)-induced asthma in mice. Fifty mice were randomly assigned to five experimental groups: control group, model group, dexamethasone (2 mg/kg) group and CH (5 and 10 mg/kg) groups. The number of eosinophil cells and the production of interleukin-6 (IL-6), IL-1ß, IL-17 A and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) were measured. In addition, pulmonary histopathology, airway resistance (Raw), T-helper17 (Th17) cells frequency and RORγt expression were evaluated. Our study demonstrated that CH effectively decreased eosinophil count and inflammatory cytokines production in BALF. In addition, treatment with CH significantly inhibited the Raw, Th17 percentage and RORγt expression in OVA-induced animals compared with those in model group. Histological studies also demonstrated that CH significantly suppressed OVA-induced eosinophilia in lung tissue compared with model group. Our findings supported that CH can prevent allergic asthma in the mouse model.

Relationship of microRNA 616 gene polymorphism with prognosis of patients with premature coronary artery disease.

OBJECTIVE: To investigate the relationship of microRNA 616 (has-miR-616) single nucleotide polymorphisms (SNPs) and its target gene paraoxonase 1 (PON 1) with the prognosis of patients with premature coronary artery disease (pCAD). METHODS: 266 pCAD cases in the case group and 300 cases in the control group were collected. Using the polymorphism method of polymerase chain reaction and restriction fragment length, the has-miR-616 rs3735590 genotypes of target gene PON 1 were detected. RESULTS: In the changes of rs3735590 C/T SNPs, compared with CC genotypes, the risk of coronary heart disease of the individuals carrying CT and TT genotypes were reduced by 42% and 31%, respectively (p < 0.05). The risk of developing coronary heart disease in individuals carrying CT and TT genotypes were reduced significantly in the population with levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. CONCLUSION: Target gene PON 1 of hsa-miRNA-616 rs3735590C-T SNPs is associated with the reduced incidence risk of pCAD, and carrying C alleles is an independent risk factor for pCAD.

Predictive models and spatial variations of vital capacity in healthy people from 6 to 84 years old in China based on geographical factors.

The aim of this study was to provide a scientific basic for a unified standard of the reference value of vital capacity (VC) of healthy subjects from 6 and 84 years old in China. The normal reference value of VC was correlated to seven geographical factors, including altitude (X1), annual duration of sunshine (X2), annual mean air temperature (X3), annual mean relative humidity (X4), annual precipitation amount (X5), annual air temperature range (X6) and annual mean wind speed (X7). Predictive models were established by five different linear and nonlinear methods. The best models were selected by t-test. The geographical distribution map of VC in different age groups can be interpolated by Kriging's method using ArcGIS software. It was found that the correlation of VC and geographical factors in China was quite significant, especially for both males and females aged from 6 to 45. The best models were built for different age groups. The geographical distribution map shows the spatial variations of VC in China precisely. The VC of healthy subjects can be simulated by the best model or acquired from the geographical distribution map provided the geographical factors for that city or county of China are known.

Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6.

Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. Considering the anti-inflammatory and antioxidant properties of Dex, we applied in vivo rat model as well as in vitro cardiomyocyte models (embryonic rat cardiomyocytes H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial ischemia reperfusion (I/R) injury. Transcriptomic sequencing for gene expression in heart tissues from control rats and Dex-treated rats identified that genes related to fatty acid metabolism were significantly regulated by Dex. Among these genes, the elongation of long-chain fatty acids (ELOVL) family member 6 (Elovl6) was most increased upon Dex-treatment. By comparing the effects of Dex on both wild type and Elovl6-knockdown H9c2 cells and NRCMs under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, we found that Elovl6 knockdown attenuated the protection efficiency of Dex, which was supported by the cytotoxicity endpoints (cell viability and lactate dehydrogenase release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays a key role in the process, which was further confirmed using palmitate exposure in both cells, as well as in an in vivo rat model. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provides better understanding on the fatty acid metabolism underlying the beneficial effects of Dex.

The association between lymphocyte-to-monocyte ratio and all-cause mortality in obese hypertensive patients with diabetes and without diabetes: results from the cohort study of NHANES 2001-2018.

Objective: Obesity, hypertension and diabetes are high prevalent that are often associated with poor outcomes. They have become major global health concern. Little research has been done on the impact of lymphocyte-to-monocyte ratio (LMR) on outcomes in these patients. Thus, we aimed to explore the association between LMR and all-cause mortality in obese hypertensive patients with diabetes and without diabetes. Methods: The researchers analyzed data from the National Health and Nutrition Examination Survey (2001-2018), which included 4,706 participants. Kaplan-Meier analysis was employed to compare survival rate between different groups. Multivariate Cox proportional hazards regression models with trend tests and restricted cubic splines (RCS) analysis and were used to investigate the relationship between the LMR and all-cause mortality. Subgroup analysis was performed to assess whether there was an interaction between the variables. Results: The study included a total of 4706 participants with obese hypertension (48.78% male), of whom 960 cases (20.40%) died during follow-up (median follow-up of 90 months). Kaplan-Meier curves suggested a remarkable decrease in all-cause mortality with increasing LMR value in patients with diabetes and non-diabetes (P for log-rank test < 0.001). Moreover, multivariable Cox models demonstrated that the risk of mortality was considerably higher in the lowest quartile of the LMR and no linear trend was observed (P > 0.05). Furthermore, the RCS analysis indicated a non-linear decline in the risk of death as LMR values increased (P for nonlinearity < 0.001). Conclusions: Increased LMR is independently related with reduced all-cause mortality in patients with obese hypertension, regardless of whether they have combined diabetes.

Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting.

BACKGROUND: Atrial arrhythmia (AA) is the most common complication after coronary artery bypass grafting (CABG). Only beta-blockers and amiodarone have been convincingly shown to decrease its incidence. The effectiveness of magnesium on this complication is still controversial. This meta-analysis was performed to evaluate the effect of magnesium as a sole or adjuvant agent in addition to beta-blocker on suppressing postoperative AA after CABG. METHODS: We searched the PubMed, Medline, ISI Web of Knowledge, Cochrane library databases and online clinical trial database up to May 2012. We used random effects model when there was significant heterogeneity between trials and fixed effects model when heterogeneity was negligible. RESULTS: Five randomized controlled trials were identified, enrolling a total of 1251 patients. The combination of magnesium and beta-blocker did not significantly decrease the incidence of postoperative AA after CABG versus beta-blocker alone (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.86-1.47, P = 0.40). Magnesium in addition to beta-blocker did not significantly affect LOS (weighted mean difference -0.14 days of stay, 95% CI -0.58 to 0.29, P = 0.24) or the overall mortality (OR 0.59, 95% CI 0.08-4.56, P = 0.62). However the risk of postoperative adverse events was higher in the combination of magnesium and beta-blocker group than beta-blocker alone (OR 2.80, 95% CI 1.66-4.71, P = 0.0001). CONCLUSIONS: This meta-analysis offers the more definitive evidence against the prophylactic administration of intravenous magnesium for prevention of AA after CABG when beta-blockers are routinely administered, and shows an association with more adverse events in those people who received magnesium.

The spatial distribution of interleukin-4 (IL-4) reference values in China based on a back propagation (BP) neural network.

This study aimed to investigate the geospatial distribution of normal reference values of Interleukin 4 (IL-4) in healthy Chinese adults and to provide a basis for the development of standard references. IL-4 values of 5,221 healthy adults from 64 cities in China were collected and analyzed for a potential correlation with 24 topographical, climatic and soil factors. Seven of these factors were extracted and used to build a back propagation (BP) neural network model that was used to predict IL-4 reference values in healthy individuals from 2,317 observation sites nationwide. The predicted values were tested for normality and geographic distribution by analytic Kriging interpolation to map the geographic distribution of IL-4 reference values in healthy Chinese subjects. The results showed that IL-4 values generally decreased and then increased from the South to the North. We concluded that the BP neural network model applies to this approach, where certain geographical factors determine levels of various biochemical and immunological standards in healthy adults in regions with different topography, climate and soil indices.