A novel lncRNA MDHDH suppresses glioblastoma multiforme by acting as a scaffold for MDH2 and PSMA1 to regulate NAD+ metabolism and autophagy.

BACKGROUND: To identify potential targets related to nicotinamide adenine dinucleotide (NAD+) metabolism in gliomas, we used RNA immunoprecipitation to identify a novel long noncoding RNA renamed malate dehydrogenase degradation helper (MDHDH) (NONCODE annotation ID: NONHSAT138800.2, NCBI Reference Sequence: NR_028345), which bound to MDH2 (malate dehydrogenase 2), that is downregulated in glioblastoma multiforme (GBM) and associated with metabolic regulation. However, its underlying mechanisms in the progression of GBM have not been well studied. METHODS: To investigate the clinical significance of MDHDH, we analyzed its expression levels in publicly available datasets and collected clinical samples from Shandong Provincial Hospital, affiliated with Shandong University. Functional assays, including FISH/CISH, CCK8, EdU, wound healing, and transwell assays, were used to determine the cellular/subcellular localization, tissue expression profile and anti-oncogenic role of MDHDH. Furthermore, RNA pulldown, mass spectrometry RNA immunoprecipitation, coimmunoprecipitation, JC-1 probe, and cell energy-production assays were used to determine the mechanisms of MDHDH in the development of GBM. Animal experiments were conducted to determine the antitumorigenic role of MDHDH in GBM in vivo. RESULTS: In public datasets, MDHDH expression was significantly downregulated in GBM and LGG compared with GTEx normal brain tissues. The results of the tissue microarray showed that the MDHDH expression level negatively correlated with the tumor grade. Altered MDHDH expression led to significant changes in the proliferation, migration and invasion of GBM cells both in vitro and in vivo. Mechanistically, we found that MDHDH directly bound to MDH2 and PSMA1 (20S proteasomal core subunit alpha-type 1) as a molecular scaffold and accelerated the degradation of MDH2 by promoting the binding of ubiquitinated MDH2 to the proteasome. The degradation of MDH2 subsequently led to changes in the mitochondrial membrane potential and NAD+/NADH ratio, which impeded glycolysis in glioma cells. CONCLUSIONS: In conclusion, this study broadened our understanding of the functions of lncRNAs in GBM. We demonstrated that the tumor suppressor MDHDH might act as a clinical biomarker and that the overexpression of MDHDH might be a novel synergistic strategy for enhancing metabolism-based, epigenetic-based, and autophagy regulation-based therapies with clinical benefits for glioblastoma multiforme patients.

The Risk of Postpolypectomy Bleeding in Patients Receiving Direct Oral Anticoagulants compared to Warfarin or Nonanticoagulation: A Systematic Review with Meta-Analysis.

AIM: The aim of our systematic review and meta-analysis was to assess the risk of postpolypectomy bleeding (PPB) in patients exposed to direct oral anticoagulants (DOACs). METHODS: A systematic search was conducted by searching the PubMed, Embase, and Cochrane Library databases using the following search terms: "(nonvitamin K antagonist oral anticoagulants or NOAC or apixaban or dabigatran or rivaroxaban or edoxaban or DOAC or direct oral anticoagulants) and polypectomy". Studies evaluating the association between DOACs and PPB were identified. RESULTS: The bibliographical search yielded 103 studies. Twelve studies involving 621,279 participants were ultimately included (11 cohort studies, of which 10 were retrospective, and a randomized controlled trial.). Pooled estimates revealed a higher risk of PPB among patients using DOACs than among those without anticoagulation (odds ratio [OR]: 6.170, 95% confidence interval [CI]: 3.079 to 12.363). The same result occurred when DOACs were stopped 24 hours before polypectomy (OR: 8.66, 95% CI: 4.588 to 16.348). No significant difference was noted between overall DOACs and warfarin (OR 0.826, 95% CI 0.583 to 1.172), while for subgroups, dabigatran showed a lower PPB rate than warfarin (OR: 0.582, 95% CI: 0.340 to 0.994). CONCLUSIONS: DOACs can significantly raise the risk of PPB, even with 24-hour withdrawal before polypectomy. In addition, a lower risk of PPB was detected for dabigatran than for warfarin.

[Particle Size Distribution and Diffusion for Simulated Cooking Fume].

Studying particle size distribution and dispersion characteristics of cooking oil fume can help to analyze the influence of the particles on indoor air quality and the health of the residents.Electrical low pressure impactor (ELPI) was employed to measure the number and mass concentration of the particles size range of 0.03-10 µm at two different locations in the kitchen space with smoke exhaust on and off,respectively.The cooking particles were mostly located at below 655 nm.The smoke exhaust with open condition could remarkably decrease the kitchen's cooking fume.The number concentration of particles decreased from 2.8×106 cm-3 to 2.3×105 cm-3,and PM2.5(aerodynamics diameter ≤2.5 µm particulate matter) mass concentrations decreased from 85.9 mg·m-3 to 6.2 mg·m-3.The sucking efficiency of smoke exhaust for PM10 was higher than PM2.5.The number concentration of particles could be declined by 65%,and the cooking fume of PM2.5 could be declined by 75% during the diffusion process detected at the area of 3 m far away from the area where cooking took place.The distribution of PM2.5 mass concentration field of oil fume was simulated by computational fluid dynamics.The temperature field distribution of oil fume was monitored by infrared camera,presenting sector diffusion with the temperature decreasing from 70℃ to room temperature.

[Emission Characteristics of Vehicles from National Roads and Provincial Roads in China].

In recent years, with the rapid increase in automobile volume, vehicle emissions have become one of the major emission sources of urban air pollution in China. In China, most of the national and provincial roads have been the channels that connect different cities. Up until 2015, the length of national and provincial roads have reached 1.85×105 km and 3.29×105km, respectively, accounting for 13% of the mileage of all classified highways. Therefore, active research on vehicle emissions from national and provincial roads between cities in China is of great significance. Few studies have been conducted on air pollutant emissions from intercity vehicles. In this study, emission characteristics of intercity vehicles were investigated based on traffic monitoring data and the "calculation guide of air pollutant emission for road vehicles". The results showed that the CO, NOx, PM, and HC emissions accounted for 4.5%, 27.9%, 14.4%, and 7.7% of national vehicle emissions, respectively. There were significant differences in emission contributions among different types of intercity vehicles. Heavy trucks were major contributors to NOx, PM10, and PM2.5 emissions and motorcycles contributed most to CO and HC. Furthermore, there were significant differences in emission contributions of vehicle types on different road types; the major contributor of CO and HC emissions was small passenger cars on expressways. Motorcycles were the main contributors to CO and HC emissions on ordinary roads.

Associations of lipid levels susceptibility loci with coronary artery disease in Chinese population.

BACKGROUND: Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that were associated with blood lipid levels in Caucasians. This study investigated whether these loci influenced lipid levels and whether they were associated with the risk of coronary artery disease (CAD) and its angiographic severity in Chinese population. METHODS: Six SNPs were genotyped in 1100 CAD cases and 1069 controls using the high-resolution melting (HRM) method. Coronary atherosclerosis severity was assessed by the vessel scores and the Gensini scoring system. RESULTS: Among the 6 SNPs and the genetic risks scores (GRS), the minor alleles of HNF1A rs1169288 (odd ratio (OR) = 1.18, 95% confidence interval (CI) 1.05-1.33, P = 0.006) and MADD-FOLH1 rs7395662 (OR = 1.20, 95% CI 1.07-1.36, P = 0.002) as well as the GRS (P = 1.06 × 10(-5)) were significantly associated with increased risk of CAD after false discovery rate (FDR) correction. The vessel (P = 0.013) and Gensini scores (ß = 0.113, P = 0.002) differed among CAD patients with different SNP rs1169288 C > T genotypes. The multiple linear regression analyses using an additive model revealed that the minor allele C of SNP rs1169288 (ß = 0.060, P = 0.001) and the GRS (ß = 0.033, P = 3.59 × 10(-4)) were significantly associated with increased total cholesterol (TC) levels, the minor allele A of SNP rs7395662 (ß = -0.024, P = 0.007) and the GRS (ß = -0.013, P = 0.004) were significantly associated with decreased high-density lipoprotein cholesterol (HDL-c) levels. CONCLUSIONS: The present study demonstrated that SNPs rs1169288, rs7395662 and the GRS were significantly associated with lipid levels and the risk of CAD in Chinese population. Furthermore, the allele C of SNP rs1169288 increased the odds of coronary atherosclerosis severity.

Effects of add-on lipid-modifying therapy on top of background statin treatment on major cardiovascular events: A meta-analysis of randomized controlled trials.

BACKGROUND: In patients at high risk of atherosclerotic cardiovascular diseases (ASCVDs), residual cardiovascular risk persists despite the achievement of target LDL cholesterol levels with statin therapy. It is still unclear whether adding lipid-modifying agent to statin treatment can further improve clinical outcomes. METHODS: Randomized controlled trials (RCTs) in terms of adding lipid-modifying agent to statin versus statin monotherapy in patients at high risk of ASCVD were identified by electronic and manual searches. Results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Eleven RCTs with 109,244 patients were included in this meta-analysis. Overall, the incidences of major adverse cardiovascular events (MACEs) were 9.70% in the statin combination groups and 9.92% in the statin monotherapy groups. No significant difference was observed in the risk of MACEs either in overall (RR 0.99, 95% CI 0.93-1.05, P=0.76) or subgroup analysis (CETP inhibitor: RR 1.07, 95% CI 0.93-1.23, P=0.37; niacin: RR 1.03, 95% CI 0.85-1.25, P=0.79; n-3 fatty acid: RR 0.98, 95% CI 0.88-1.09, P=0.70; fenofibrate: RR 0.93, 95% CI 0.80-1.09, P=0.38), with the exception of the statin/ezetimibe combination subgroup (RR 0.92, 95% CI 0.87-0.97, P=0.004). Adding lipid-modifying agent to statin significantly increased liver injury risk. Adding ezetimibe to statin did not alter side effect profile. CONCLUSION: Adding niacin, CETP inhibitors, n-3 fatty acid or fibrates to statin therapy has all failed to achieve a clinical benefit. Adding ezetimibe to statin therapy further lowers LDL-cholesterol safely and translates into a clinical benefit in patients at high risk of ASCVD.

[Spatial distribution of Se in soils from different land use types and its influencing factors within the Yanghe Watershed, China].

Based on different land use types, altitudes, soil and vegetation types etc, 171 representative topsoils (0-10 cm) were collected within the Yanghe watershed, China for determining the total concentrations, spatial distribution and influencing factors of selenium (Se). The results showed that the total selenium concentrations in soils within the watershed ranged from 0.02 to 3.24 mg x kg(-1) dry weight (dw). The geometric mean of Se in soils within the watershed was 0.30 mg x kg(-1), which was higher than those in Beijing plain (0.20 mg x kg(-1)), Hebei plain (0.19 mg x kg(-1)) and China (0.29 mg x kg(-1)). Soils which lacked Se (0.13-0.18 mg x kg(-1)) were mainly distributed in Huaian, Xuanhua, and Huailai counties. Se concentrations in most areas within the watershed were sufficient (0.18-0.45 mg x kg(-1)). In addition, Wanquan, Xinghe, Tianzhen and Yanggao counties also had some selenium-rich areas. Concentrations of Se were different under different land use types. They were of the following order: forest land > industrial and mining land > grassland > agricultural land. Agricultural land had the lowest concentrations of Se, with a mean concentration of 0.28 mg x kg(-1). We also found that parent materials and soil types had no significant effects on soil Se concentrations within the Yanghe Watershed. The results indicated that Se concentrations were positively and significantly correlated with clay contents and altitudes, but negatively and significantly with pH values. Furthermore, TOC, Fe and Al concentrations were also important factors influencing the Se concentrations in soils within the Yanghe Watershed.

Role of pre-procedural C-reactive protein level in the prediction of major adverse cardiac events in patients undergoing percutaneous coronary intervention: a meta-analysisof longitudinal studies.

Numerous studies have reported the relation between pre-procedural C-reactive protein (CRP) levels and the risk of major adverse cardiac events (MACEs) in patients undergoing percutaneous coronary intervention (PCI). However, the results across the studies were inconsistent. The aim of this study was to evaluate the predictive effect of pre-procedural CRP levels and the risk of MACEs in patients undergoing PCI. Longitudinal studies on the association between pre-procedural CRP levels and MACEs were identified by electronic and manual searches. Summary risk ratios (RRs) and 95 % confidence intervals (CI) were calculated employing an inverse variance random-effects model irrespective of between-study heterogeneity. Thirty-three studies involving 34,367 patients with 4119 MACEs were included in this study. High CRP level was associated with increased incidences of MACEs, all-cause death, myocardial infarction, coronary revascularization, and clinical restenosis, with pooled RRs of 1.97 (95 % CI, 1.65, 2.35), 2.88 (95 % CI, 2.15, 3.86), 1.81 (95 % CI, 1.48, 2.21), 1.31 (95 % CI, 1.11, 1.56), and 1.45 (95 % CI, 1.07, 1.96), respectively. Dose-response analysis showed that every 1 mg/L increment in pre-procedural serum CRP level was associated with a significant 12 % increase in the risk of MACEs. In spite of heterogeneity across the included studies, this meta-analysis suggests that pre-procedural serum CRP level is a valuable predictor of MACEs in patients undergoing PCI.

Angiotensin-converting enzyme gene polymorphisms and risk for sporadic Alzheimer's disease: a meta-analysis.

Numerous studies have tested for associations between common polymorphisms of the angiotensin-converting enzyme gene and sporadic Alzheimer disease (SAD), but results have been inconclusive. Using meta-analysis, our study aimed to clarify the nature of the genetic risks contributed by the three polymorphisms (rs4291, rs4343, rs1800764) for developing SAD. Through searching of Pubmed, Embase, Alzgene and manually searching relevant references, a total of 14 articles with 26 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association studies. The heterogeneity across the studies was tested, as was publication bias. We observed significant association between SNP rs4291 and SAD using allelic comparison (OR = 1.08, 95% CI 1.03-1.14), homozygote comparison (OR = 1.16, 95% CI 1.04-1.30) and the recessive model (OR = 1.10, 95% CI 1.02-1.18). Association with SNP rs1800764 was revealed but it was not sufficiently robust to withstand the Benjamini-Hochberg method and stepdown Bonferroni correction. Significant association was not identified in the analysis for SNP rs4343. In subgroup analyses, the risk of SAD associated with SNP rs4291 appeared to be significant among Caucasians and in older cases (mean age ≥75 years). Our results confirmed a significant but modest association between SNP rs4291 and SAD susceptibility. Further study of the pathogenetic characteristics of this polymorphism and independent confirmation of the association in larger studies are warranted.

Angiotensin-converting enzyme insertion/deletion polymorphism is not a major determining factor in the development of sporadic Alzheimer disease: evidence from an updated meta-analysis.

Angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism have long been linked to sporadic Alzheimer disease (SAD), but the established data remained controversial. To clarify this inconsistency, a comprehensive meta-analysis was conducted. Through searching of Pubmed, Embase, Alzgene, China National Knowledge Infrastructure (CNKI) and manually searching relevant references, 53 independent studies from 48 articles were included, involving a total of 8153 cases and 14932 controls. The strength of association was assessed by using odds ratios (ORs) with 95% confidence intervals (CIs). Further stratified analyses and heterogeneity analyses were tested, as was publication bias. Overall, significant associations were revealed between I/D polymorphism and SAD risk using allelic comparison (OR = 1.09, 95%CI = 1.01-1.17, p = 0.030), homozygote comparison (OR = 1.17, 95%CI = 1.01-1.34, p = 0.030) and the dominant model (OR = 1.16, 95%CI = 1.04-1.29, p = 0.008), but they were not sufficiently robust to withstand the false-positive report probability (FPRP) analyses. Otherwise, in subgroup analyses restricted to the high quality studies, the large sample size studies and studies with population-based controls, no significant association was observed in any genetic models. In summary, the current meta-analysis suggested that the ACE I/D polymorphism is unlikely to be a major determining factor in the development of SAD.

Non-invasive detection of EGFR deletion at exon 19 in non-small cell lung cancer by real time diagnostic.

BACKGROUND: The non-invasive identification of epidermal growth factor receptor (EGFR) mutations is important for the institution of individualized therapy of non-small cell lung cancer (NSCLC). In this study, the feasibility of screening for EGFR exon 19 E746_A750del mutations in circulating DNA from plasma was assessed. METHODS: Mutant-specific primers with a Taqman probe (MST-PCR) were designed. The ability of this method to accurately detect decreasing concentrations of E746_A750del mutant within a wild type DNA background that mimics the situation of a plasma sample from patients with acquired mutations is verified. To verify the clinical applicability of this method, 55 plasma samples from NSCLC patients were tested, and the sensitivity of MST-PCR was compared to that of direct sequencing. RESULTS: The results showed that MST-PCR could detect 10 to 50 copies/microL of E746_A750del, representing 0.1% of the wild type EGFR allelic population. Among the 55 cases of NSCLC, 10 cases of E746_A750del were detected by MST-PCR, while only 1 case was revealed by direct sequencing. CONCLUSIONS: These findings demonstrate that MST-PCR provides superior sensitivity for the detection of the E746_A750del mutation, suggesting its potential application in the noninvasive detection of E746_A750del mutations in plasma samples from NSCLC patients.

SMN1 duplications contribute to sporadic amyotrophic lateral sclerosis susceptibility: evidence from a meta-analysis.

OBJECTIVE: To investigate the association between SMN1 and SMN2 copy number variations (CNVs) and sporadic amyotrophic lateral sclerosis (SALS) by a meta-analysis. METHODS: Through searching PubMed and EMBASE database (or manual searching) up to November 2013 using the following keywords: "survival motor neuron gene", "SMN", and "amyotrophic lateral sclerosis", "ALS" or "motor neuron disease". Nine studies were identified as eligible for this meta-analysis. The association between SMN genes and the SALS risk was investigated based on SMN1 and SMN2 CNVs. The heterogeneity across the studies was tested, as was publication bias. RESULTS: The analysis showed significant association for SMN1 duplications in SALS risk: the risk estimates were OR=1.76, 95%CI=1.33-2.32, p<0.0001 (still significant when the p value was Bonferroni adjusted to 0.01). However, there was no significant association between SMN1 deletions and SALS risk after Bonferroni correction (OR=1.78, 95%CI=1.02-3.11, p=0.04). In addition, SMN2 copy number statuses were not associated with SALS in our pooled study. No evidence of publication bias was observed. CONCLUSION: Our meta-analysis suggested that SMN1 duplications are a genetic risk factor in SALS, while there was no modulator effect of the SMN2 gene. In addition, it was possible that SMN1 deletions in predisposition to SALS vary across different countries. More studies were required to warrant the findings of this study.

[Estimation inventory of polycyclic aromatic hydrocarbons (PAHs) from anthropogenic sources and its impacts within the Yanghe Watershed, an important water-source site of Beijing, China].

The Yanghe Watershed, situated at the upwind of Beijing, is an important water-source site and ecologic protection barrier for Beijing and Zhangjiakou cities. The Yanghe Watershed is also a farming-pastoral transitional area and an ecologically vulnerable and sensitive region, as well as the place applying for Winter Olympic Game in 2022. Establishment of atmospheric emissions inventory of polycyclic aromatic hydrocarbons (PAHs) and identification of its sources within the Yanghe Watershed and its possible transportation paths to Beijing can help us get a better understanding of regional environmental pollution (especially air environmental pollution) in Beijing-Zhangjiakou area. In the present study, PAHs emission from different counties and cities within the Yanghe Watershed in 2012 was calculated based on the statistical data of local industries, agriculture and resident living while PAHs emission factors were estimated. According to the cluster analysis for air transport trajectories, main categories of air masses were obtained. Results indicated that total emission of PAHs in 2012 was 4.4 x 10(2) t. Coal combustion and crop-straw burning were the most important emission sources of PAHs, accounting for 76% and 16% of total emission of PAHs, respectively. Xuanhua county had the greatest emission of PAHs (49 t), followed by Xinghe (36 t), Tianzhen (32 t), Huailai (24 t) and Wanquan (15 t). In emission of 16 isomers of PAHs, the emission of high molecular weight isomers containing 4-6 rings was approximate to that of low molecular weight isomers containing 2-3 rings, accounting for approximately 50% of total emission of PAHs. Emission of PAHs had positive correlations with gross industrial production (GIP) (r = 0.96, P < 0.05) and resident income (RI) (r = 0.94, P < 0.05) and population density (PD) (r = 0.92, P < 0.05), but negatively correlated with land area (LA) (r = - 0.9, P < 0.05) and no significant correlationship with gross output value of agriculture (GOA) (r = 0.026, P > 0.01). The high emission of PAHs within the Yanghe Watershed was associated with local energy structure and residents' consumption level. Combined the back trajectory analysis with PAHs emission, high amount of PAHs could be transported to Beijing by northwest airflow, suggesting its potential ecological risk and human health effect in Beijing.