NEAT1 regulates VSMC differentiation and calcification in as long noncoding RNA NEAT1 enhances phenotypic and osteogenic switching of vascular smooth muscle cells in atherosclerosis via scaffolding EZH2.

Atherosclerosis (AS) is a significant contributor to cardio-cerebrovascular ischemia diseases, resulting in high mortality rates worldwide. During AS, vascular smooth muscle cells (VSMCs) play a crucial role in plaque formation by undergoing phenotypic and osteogenic switching. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has previously been identified as a nuclear regulator that promotes tumorigenesis and metastasis, but its role in regulating VSMCs in AS remains unclear. Our study aimed to investigate the biological functions and specific mechanisms of NEAT1 in regulating VSMCs in AS. We found that NEAT1 was upregulated in the aortas of AS mouse models and dedifferentiated primary VSMCs. Silencing NEAT1 in vitro attenuated the proliferation, migration, and osteogenic differentiation of VSMCs, while NEAT1 overexpression had the opposite effect. Furthermore, NEAT1 promoted VSMC osteogenic differentiation and vascular calcification in both in vivo and in vitro vascular calcification models. We also discovered that NEAT1 directly activates enhancer of zeste homolog 2 (EZH2), an epigenetic enzyme that suppresses the expression of senescence- and antimigration-related genes, by translocating it into the nucleus. CUT&Tag assay revealed that NEAT1 guides EZH2 to the promoters of senescence-related genes (P16, P21, and TIMP3), methylating local histones to reduce their transcription. Our findings suggest that NEAT1 functions in AS by modulating the epigenetic function of EZH2, which enhances the proliferation, migration, and osteogenic differentiation of VSMCs. This study provides new insights into the molecular mechanisms underlying the pathogenesis of AS and highlights the potential of NEAT1 as a therapeutic target of AS.NEW & NOTEWORTHY Our study demonstrates that the upregulation of long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes proliferation and migration during phenotypic switching of vascular smooth muscle cells in atherosclerosis. We also provide in vivo and in vitro evidence that NEAT1 accelerates vascular calcification. Our findings identified the direct interaction between enhancer of zeste homolog 2 (EZH2) and NEAT1 during atherosclerosis. NEAT1 is necessary for EZH2 to translocate from the cytoplasm to the nucleus, where EZH2 epigenetically inhibits the expression of genes related to senescence and antimigration.

Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region.

Cardiac fibrosis, a well-known major pathological process that ultimately leads to heart failure, has attracted increasing attention and focus in recent years. A large amount of research indicates that long noncoding RNAs (lncRNAs) play an important role in cardiac fibrosis, but little is known about the specific function and mechanism of the lncRNA NEAT1 in the progression of cardiac fibrosis to heart failure. In the present study, we have demonstrated that the lncRNA NEAT1 is upregulated in patients with heart failure. Similarly, the expression of Neat1 was also increased in the left ventricular tissue of transverse aortic constriction (TAC) surgery mice and cardiac fibroblasts treated with TGF-ß1. Further, gain-of-function and loss-of-function experiments showed that silencing of Neat1 attenuated cardiac fibrosis, while overexpression of Neat1 with adenovirus significantly aggravated the in vitro progression of fibrosis. With regard to the underlying mechanism, our experiments showed that Neat1 recruited EZH2 to the promoter region of Smad7 through physical binding of EZH2 to the promoter region, as a result of which Smad7 expression was inhibited and the progression of cardiac fibrosis was ultimately exacerbated. We found that the introduction of shNeat1 carried by adeno-associated virus-9 significantly ameliorated cardiac fibrosis and dysfunction caused by TAC surgery in mice. Overall, our study findings demonstrate that the lncRNA Neat1 accelerates the progression of cardiac fibrosis and dysfunction by recruiting EZH2 to suppress Smad7 expression. Thus, NEAT1 may serve as a target for the treatment of cardiac fibrosis.

Therapeutic Efficacy of a Staged Hybrid Technique vs. Coronary Artery Bypass Surgery Grafting in The Treatment of Multi-Vessel Coronary Artery Disease.

OBJECTIVE: Hybrid coronary revascularization (HCR) integrates the advantages of coronary artery bypass surgery grafting (CABG) and percutaneous coronary intervention (PCI) and provides another effective treatment for multi-vessel coronary artery disease (CAD). This study aimed to investigate the short- and intermediate-term efficacies of a staged hybrid technique vs. CABG in treating older patients with multi-vessel CAD. METHODS: Patients, who received elective revascularization for multi-vessel CAD between May 2016 and May 2018, were recruited. They were divided into the CABG group (N = 38) and HCR group (N = 38). The major adverse cardiovascular and cerebrovascular events (MACCE), including myocardial infarction and stroke, were recorded. The results of death and second revascularization also were recorded. RESULTS: In this study, 90.1% of patients received follow up for a median time of 24 months. At 60 days after surgery, the cumulative mortality in the CABG group was significantly higher than in the HCR group, but the incidence of second revascularization in the CABG group was markedly lower than in the HCR group. The incidence of MACCE was comparable between the two groups. CONCLUSION: In older patients with multi-vessel CAD, the mortality after CABG is higher than after HCR, but the incidence of second revascularization after CABG is lower than after HCR.

[Protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation injury and its mechanism].

This project aimed to explore the protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation(H/R)-induced H9 c2 cardiomyocyte injury and its underlying signaling pathway. The H/R model of H9 c2 cardiomyocytes was established and then the cells were divided into different treatment groups. CCK-8(cell counting kit-8) was used to detect the activity of cardiomyocytes; Brdu assay was used to detect the proliferation of H9 c2 cells; the caspase-3 activity was tested, and then the protein expression was assessed by Western blot. Flow cytometry was used to evaluate the apoptosis level of cardiomyocytes. Ginsenoside Rg_1 inhibited H/R-induced cardiomyocyte apoptosis and caspase-3 activity, promoted nuclear transcription of nuclear factor erythroid-2 related factor 2(Nrf2), and enhanced the expression of the downstream heme oxygenase-1(HO-1). Ginsenoside Rg_1 could increase Nrf2 nuclear transcription and HO-1 expression with the increase of concentration(10, 20, 40, 60 µmol·L~(-1)). However, the protective effect of ginsenoside Rg_1 on cardiomyocytes was significantly weakened after the transfection of Nrf2-siRNA. Ginsenoside Rg_1 could protect cardiomyocytes by activating the Nrf2/HO-1 pathway.

MFGE8 attenuates Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-ß1/Smad2/3 pathway.

Atrial fibrillation (AF) is characterized by potentiated growth of atrial fibroblasts and excessive deposition of the extracellular matrix. Atrial fibrosis has emerged as a hallmark of atrial structural remodeling linked to AF. Nonetheless, the specific mechanism underlying the progression of atrial fibrosis to AF is still largely unknown. MFGE8 (milk fat globule-EGF factor 8) is a soluble glycoprotein associated with many human diseases. Recently, a number of studies revealed that MFGE8 plays a crucial role in heart disease. Yet, MFGE8 regulation and function in the process of atrial fibrosis and vulnerability to AF remain unexplored. In this study, we found that the expression of MFGE8 was downregulated in the atriums of patients with AF compared with individuals without AF. In addition, the expression of MFGE8 was lower in atriums of angiotensin II (Ang-II)-stimulated rats as compared with the sham group. In vitro, silencing of MFGE8 by small interfering RNA significantly increased Ang-II-induced atrial fibrosis, whereas administration of recombinant human MFGE8 (rhMFGE8) attenuated the atrial fibrosis. Moreover, we found that the activated TGF-ß1/Smad2/3 pathway after Ang-II treatment was significantly potentiated by the MFGE8 knockdown but inhibited by rhMFGE8 in vitro. Inhibition of integrin ß3 which is the receptor for MFGE8, suppressed the TGF-ß1/Smad2/3 activating effects of the MFGE8 knockdown in Ang-II-treated rat atrial fibroblasts. Finally, we administered rhMFGE8 to rats; it attenuated atrial fibrosis and remodeling and further reduced AF vulnerability induced by Ang-II, indicating that MFGE8 might have the potential both as a novel biomarker and as a therapeutic target in atrial fibrosis and AF.

MALAT1 Modulates TGF-ß1-Induced Endothelial-to-Mesenchymal Transition through Downregulation of miR-145.

BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) plays significant roles under various pathological conditions including cardiovascular diseases, fibrosis, and cancer. EndMT of endothelial progenitor cells (EPCs) contributes to neointimal hyperplasia following cell therapy Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that promotes metastasis and cancer. MicroRNA-145 (miR-145) is a tumor suppressor that has been reported to inhibit SMAD3-mediated epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, we investigated the role of MALAT1 and miR-145 in EndMT of human circulating EPCs induced by transforming growth factor beta1 (TGF-ß1). METHODS: Human circulating EPCs were isolated and characterized by fluorescence-activated cell sorting (FACS). Expression levels of EndMT markers were assessed by qRT-PCR and western blotting. Alpha-smooth muscle actin (α-SMA) expression was measured by cell immunofluorescence staining. The regulatory relationship between MALAT1 and miR-145 and its target genes, TGFBR2 (TGFß receptortype II) and SMAD3 (mothers against decapentaplegic homolog 3) was analyzed using the luciferase reporter assay. RESULTS: We found that EndMT of EPCs induced by TGF-ß1 is accompanied by increased MALAT1 expression and decreased miR-145 expression, and MALAT1 and miR-145 directly bind and reciprocally repress each other in these cells. Dual-Luciferase Reporter assay indicated that miR-145 inhibits TGF-ß1-induced EndMT by directly targeting TGFBR2 and SMAD3. CONCLUSIONS: MALAT1 modulates TGF-ß1-induced EndMT of EPCs through regulation of TGFBR2 and SMAD3 via miR-145. Thus, the MALAT1-miR-145-TGFBR2/SMAD3 signaling pathway plays a key role in TGF-ß1-induced EndMT.

Ginsenoside Rg1 Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury via Activation of Nrf2/HO-1 Signaling and Inhibition of JNK.

BACKGROUND/AIMS: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. METHODS: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R. In the absence or presence of Nrf2siRNA, HO-1 inhibitor (ZnPP-IX), and inhibitors of the MAPK pathway (SB203580, PD98059, SP600125), H9c2 cells were subjected to H/R with Rg1 treatment. The effects and mechanisms of H/R-induced cardiomyocyte injury were measured. RESULTS: Ginsenoside Rg1 treatment suppressed H/R-induced apoptosis and caspase-3 activation. Ginsenoside Rg1 treatment decreased ROS production and mitochondrial membrane depolarization by elevating the intracellular antioxidant capacity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH). Furthermore, ginsenoside Rg1 stimulation appeared to result in nuclear translocation of NF-E2-related factor 2 (Nrf2), along with enhanced expression of the downstream target gene heme oxygenase-1 (HO-1) in a dose-dependent manner. However, ginsenoside Rg1-mediated cardioprotection was abolished by Nrf2-siRNA and HO-1 inhibitor. H/R treatment increased the levels of phosphorylated c-Jun N-terminal kinases (p-JNK), which was dramatically attenuated by ginsenoside Rg1 and SP600125 (a specific JNK inhibitor). CONCLUSION: These observations indicate that ginsenoside Rg1 activates the Nrf2/HO-1 axis and inhibits the JNK pathway in H9c2 cells to protect against oxidative stress.

Upregulation of microRNA-34a enhances myocardial ischemia-reperfusion injury via the mitochondrial apoptotic pathway.

Mitochondrial oxidative injury can result in many cardiovascular diseases including cardiac ischemia-reperfusion (I/R) injury. This study was designed to investigate whether microRNA-34a (miR-34a) influences cardiac I/R or hypoxia/reoxygenation (H/R) injury by regulating the mitochondrial apoptotic pathway from oxidative injury.In vivo, myocardial infarction size was examined by Evan blue/TTC staining. Apoptosis was assessed by TUNEL assay. Heart function was measured by echocardiography. Lactate dehydrogenase (LDH) and creatine kinase (CK) were evaluated. In vitro, H9c2 cardiomyocytes were exposed to H/R stimulation. Cell viability was assessed by the CCK-8 assay and apoptosis was detected by Annexin V/PI staining. Mitochondrial superoxide, mitochondrial membrane potential (MMP) and ATP production was evaluated by detection kits, and related proteins were detected by western blotting analysis. We observed that the level of miR-34a was significantly upregulated in I/R rats compared to the sham group. Injection of adenovirus inhibiting miR-34a into the left ventricular anterior wall improved heart function and decreased I/R injury. H9c2 cardiomyocytes exposed to H/R stimulation displayed an obvious increase in miR-34a expression. In addition, miR-34a inhibitor alleviated, whereas miR-34a mimic aggravated H/R-induced mitochondrial injury. Bcl-2 was identified as a target gene of miR-34a by dual-luciferase reporter gene detection. Knockdown of Bcl-2 abolished the cardioprotection of the miR-34a inhibitor in H9c2 cells. In summary,our study demonstrates that inhibition of miR-34a exhibits therapeutic potential in treatment of myocardial I/R injury by restraining mitochondrial apoptosis.

LncRNA Gaplinc promotes the pyroptosis of vascular endothelial cells through SP1 binding to enhance NLRP3 transcription in atherosclerosis.

Pyroptosis, characterized by activation of the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effector inflammatory factors, has been shown to play a crucial role in atherosclerosis development. Long noncoding RNAs (lncRNAs) are involved in the progression of pyroptosis. However, the role and mechanism of the novel lncRNA gastric adenocarcinoma associated, positive CD44 regulator (Gaplinc), in endothelial cell pyroptosis during atherosclerosis development remain unexplored. Bioinformatics was performed to evaluate dysregulated lncRNAs in atherosclerotic mice fed a high-fat diet. The effect of Gaplinc on atherosclerosis progression in vivo was assessed via Oil Red O staining and fluorescence in situ hybridization. Its function in oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis of endothelial cells was determined through ectopic expression. Additionally, RNA pull-down and immunoprecipitation (RIP) assays were performed to determine Gaplinc and transcription factor SP1 interactions. Then the pyroptosis pathway proteins were analyzed via immunofluorescence and western blotting. We found that lncRNA Gaplinc was highly expressed in ox-LDL-induced endothelial cells as well as in the plaque and plasma of high-fat diet-treated ApoE-/- mice. Gaplinc silencing significantly inhibited endothelial cell pyroptosis and atherosclerotic plaque formation. Mechanistically, Gaplinc could interact with SP1 to bind to the NLRP3 promoter and upregulate the target gene expression of NLRP3, facilitating endothelial cell pyroptosis and atherosclerotic plaque enlargement in high- fat diet-fed mice. In conclusion, our results revealed the underlying mechanism of the lncRNA Gaplinc /SP1/NLRP3 axis in endothelial cell pyroptosis, which may provide new potential targets for the treatment of atherosclerosis.

Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages.

1. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) by monocytes/macrophages has been proposed to play a significant role in atherosclerotic plaque progression and rupture. The aim of the present study was to explore whether artemisinin, a natural extract from Artemisia annua, could decrease EMMPRIN and MMP-9 expression in phorbol myristate acetate (PMA)-induced macrophages by regulating the protein kinase (PK) Cδ/c-Jun N-terminal kinase (JNK)/p38/extracellular signal-regulated kinase (ERK) pathway. 2. Human monocytic THP-1 cells were pretreated with 20-80 µg/mL artemisinin for 4 h or 1-10 µmol/L rottlerin for 1 h prior to stimulation with PMA (100 nmol/L) for another 48 h. Cells were collected to analyse the induction of EMMPRIN and MMP-9. Upstream pathway analysis using the PKCδ inhibitor rottlerin detected activation of the PKCδ/JNK/p38/ERK pathway. 3. Artemisinin (20-80 µg/mL) significantly inhibited the induction of EMMPRIN and MMP-9 at both the transcriptional and translational levels in a dose-dependent manner in PMA-induced macrophages. In addition, artemisinin (20-80 µg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation. The PKCδ inhibitor rottlerin (1-10 µmol/L) also significantly inhibited JNK/p38/ERK phosphorylation and decreased EMMPRIN and MMP-9 mRNA and protein expression. 4. The results of the present study suggest that artemisinin inhibits EMMPRIN and MMP-9 expression and activity by suppressing the PKCδ/ERK/p38 cascade in PMA-induced macrophages.

Fatigue Life Prediction of Machined Specimens with the Consideration of Surface Roughness.

The fatigue strength and fatigue life of high-strength steels are greatly affected by their surface roughness. This study investigates the underlying mechanisms responsible for fatigue failure of the high-strength steel 42CrMo. Bending fatigue tests of stepped shafts with different levels of surface roughness were conducted to observe the fatigue live reduction affected by surface topography. Besides, the mechanical properties of 42CrMo and its strain-life relationship were established. Moreover, the analytical formulas to describe the stress concentration factor (SCF) and fatigue notch factor (FNF) induced by surface topography were introduced. To estimate the fatigue life of machined specimens with the consideration of surface roughness, the elastic portion of the total strain-life curve of the material was revised with the proposed analytical FNF imposed by surface topography. Comparisons between the estimated fatigue lives and experimentally obtained fatigue lives show that the effect of surface roughness on fatigue lives could be estimated effectively and conveniently by the proposed procedure.

Circ-ADAM9 targeting PTEN and ATG7 promotes autophagy and apoptosis of diabetic endothelial progenitor cells by sponging mir-20a-5p.

Dysfunction of endothelial progenitor cells (EPCs) is a key factor in vascular complications of diabetes mellitus. Although the roles of microRNAs and circular RNAs in regulating cell functions have been thoroughly studied, their role in regulating autophagy and apoptosis of EPCs remains to be elucidated. This study investigated the roles of mir-20a-5p and its predicted target circ-ADAM9 in EPCs treated with high glucose (30 mM) and in a diabetic mouse hind limb ischemia model. It is found that Mir-20a-5p inhibited autophagy and apoptosis of EPCs induced by high-concentration glucose. Further, mir-20a-5p could inhibit the expression of PTEN and ATG7 in EPCs, and promote the phosphorylation of AKT and mTOR proteins under high-glucose condition. Investigation of the underlying mechanism revealed that circ-ADAM9, as a miRNA sponges of mir-20a-5p, promoted autophagy and apoptosis of EPCs induced by high-concentration glucose. Circ-ADAM9 upregulated PTEN and ATG7 in interaction with mir-20a-5p, and inhibited the phosphorylation of AKT and mTOR to aggravate autophagy and apoptosis of EPCs under high glucose. In addition, silencing of circ-ADAM9 increased microvessel formation in the hind limbs of diabetic mice. Our findings disclose a novel autophagy/apoptosis-regulatory pathway that is composed of mir-20a-5p, circ-ADAM9, PTEN, and ATG7. Circ-ADAM9 is a potential novel target for regulating the function of diabetic EPCs and angiogenesis.

Long Noncoding RNA PVT1 as a Novel Predictor of Metastasis, Clinicopathological Characteristics and Prognosis in Human Cancers: a Meta-Analysis.

The present meta-analysis aimed to systematically evaluates the metastasis, clinical stage, and prognostic value regarding the expression levels of PVT1 in various cancers. Relevant literatures were searched in PubMed、Cochrane Library、Wed of science、Embase databases、Chinese National Knowledge Infrastructure and Wanfang from inception up to 22 August 2017. After data were extracted, a meta-analysis was performed using Review Manager 5.3 and Stata 12.0 software. The meta-analysis showed that high expression of PVT1 could predict more lymph node metastasis (LNM) (Odds ratio, OR = 2.83, 95% confidence interval, CI: 1.76-4.54, P < 0.0001), distant metastasis (DM) (OR = 3.60, 95% CI: 1.08-12.03, P = 0.04), advanced clinical stage (OR = 4.37, 95% CI: 3.45-5.54, P < 0.00001) and poor overall survival (Hazard ratio, HR = 2.08, 95% CI: 1.82-2.37, P < 0.00001)in cancer. Subgroup analysis in different systems also showed the same results, including respiratory system、digestive system、urinary system and other systems, especially in respiratory system (LNM, OR = 4.57, 95% CI: 2.41-8.68, P < 0.00001; clinical stage, OR = 5.59, 95% CI: 3.59-8.71, P < 0.00001; OS, HR = 2.43, 95% CI: 1.98-2.99, P < 0.00001). These results suggest that PVT1 could serve as a novel biomarker for metastasis, clinical stage and poor prognosis in various tumors.

Effect of Shengmai Injection on cardiac function and inflammatory reaction in patients with acute coronary syndrome.

OBJECTIVE: To confirm the effect of Shengmai Injection (, SMI) in improving cardiac function in patients with acute coronary syndrome (ACS) and to explore its influence on inflammatory reaction in patients. METHODS: Ninety ACS patients were randomized into two groups, the control group treated with conventional therapy and the SMI group treated with SMI. The patients' cardiac function was noted and the content of high sensitive C-reactive protein (hs-CRP) in venous blood was measured before treatment and 1 week and 3 weeks after treatment, so as to observe and compare their changes between the two groups. RESULTS: The cardiac output, stroke volume and ejection fraction in the SMI group after 3 weeks of treatment were all higher than those in the control group (P<0.05). The serum content of hs-CRP was reduced in both groups (P<0.05), but the reduction in the SMI group was more significant than that in the control group (P<0.05). CONCLUSION: SMI could improve the cardiac function and further inhibit the inflammatory reaction in patients with ACS.

Effect of Shengmai injection on vascular endothelial and heart functions in patients with coronary heart disease complicated with diabetes mellitus.

OBJECTIVE: To study the effect of Shengmai injection (, SMI) on vascular endothelial and heart functions in coronary heart disease patients complicated with diabetes mellitus (CHD-DM). METHODS: One hundred and twenty patients with CHD-DM, their diagnosis confirmed by coronary arteriography, were equally randomized into a control group treated with conventional treatment and a treated group treated with conventional treatment plus SMI. The changes in blood levels of nitric oxide (NO), endothelin-1 (ET-1) and angiotensin II (Ang II), as well as endothelium-dependent vascular dilating function and heart function in the patients were observed before treatment and after the 3-week treatment. RESULTS: After being treated with SMI for 3 weeks, in the treated group, blood level of NO was raised significantly from 69.8 + or - 33.1 micro mol/L to 120.1 + or - 50.8 micro mol/L, and ET-1 was lowered from 70.1 + or - 32.1 ng/L to 46.2 + or - 21.3 ng/L, respectively (P<0.01); that of Ang II was lowered from 81.3 + or - 24.3 ng/L to 50.2 + or - 27.3 ng/L (P<0.01); brachial arterial post-congestion blood flow increasing rate was raised from 389.4 + or - 26.3% to 459.3 + or - 27.8% (P<0.01); and the improvement in heart function as seen through the ejection fraction (EF) was increased from 44 + or - 5% to 68 + or - 6% (P<0.01), all the changes being more significant than those in the control group (all P<0.01). CONCLUSION: SMI can improve not only the endothelial function in CHD-DM patients, but also heart contraction significantly.

[Progress of Long Non-coding RNA in Non-small Cell Lung Cancer].

Lung cancer is one of the most important malignant tumors in the world. The morbidity and mortality rank the first in all kinds of cancer. Long non-coding RNA (lncRNA) is at least 200 nt long and has no protein coding capacity. It plays an important role in the epigenetic regulation, cell cycle regulation, the regulation of cell differentiation, and many other life activities. The studies indicate that dysregulation of lncRNAs in non-small cell lung cancer (NSCLC) tissue and blood circulation is associated with the occurrence and development of cancer. The lncRNAs play an significant role in proliferation, differentiation, migration and apoptosis of the tumor cells. Explore the potential mechanism between lncRNAs and NSCLC is beneficial for the early diagnosis, target therpy and improve prognosis. Therefore, the study aims to demonstrate the latest studies on the lncRNAs related to occurence, diagnosis, therpy and prognosis of NSCLC. It can help to deeply understanding of lncRNA, and provide new ideas for the prevention of NSCLC.

Cancer survival in Cixian of China, 2003-2013: a population-based study.

Cixian is one of the high-risk areas for upper gastrointestinal cancer in China and the world. From 2005, comprehensive population-based screening for upper gastrointestinal cancers has been conducted in Cixian. The aim of this study was to investigate population-based cancer survival from 2003 to 2013 and to explore the effect of screening on upper gastrointestinal cancer survival in Cixian. Observed survival was estimated using the life table method. The expected survival from the general population was calculated using all-cause mortality data from the population of Cixian with the EdererII method. Cixian cancer registry, with a total coverage of 6.88 million person years, recorded 19,628 cancer patients diagnosed during 2003-2013. In Cixian, from 2003 to 2013, there were 19,628 newly cancer cases and 13,984 cancer deaths, with an incidence rate of 285.37/100,000 and mortality rate of 203.31/100,000. The overall five-year relative cancer survival for patients diagnosed in Cixian in 2003-2013 was 22.53%. The relative survival for all cancers combined in Cixian had an overall upward trend from 2003 to 2013. Among upper gastrointestinal cancer in Cixian, the five-year relative survival for cardia gastric cancer was highest at 30.42%, followed by oesophageal cancer at 25.37% and noncardia gastric cancer at 18.93%. In 2013, the five-year relative survival for oesophageal cancer, cardia gastric cancer, and noncardia gastric cancer patients aged 45-69 years was 39.97% (95% CI: 34.52-45.43%), 51.74% (95% CI: 42.09-60.86%), and 37.43% (95% CI: 26.93-48.17%), respectively, the absolute values increasing 14.11%, 16.71%, and 14.92% compared with that in 2003. There is an increasing trend in overall survival for upper gastrointestinal cancer with early screening and treatment of cancer in Cixian.

Risk factors for pulmonary nodules in north China: A prospective cohort study.

OBJECTIVES: Pulmonary nodules have become common incidental findings with the widespread use of computed tomography (CT) technology. Such nodules have the potential to become early lung cancer lesions, so understanding more about factors that may be associated with them is important. MATERIALS AND METHODS: The present work was based on a large prospective cohort comprising 32,438 participants in Hebei Province (China) between January 2014 and March 2016. Participants aged 40-75 years completed a questionnaire, underwent low-dose CT (LDCT), and were followed up to March 2017. Grouped by the results of LDCT, normal participants and those with pulmonary nodules were included in the data analysis. RESULTS: In total 7752 subjects were included in this study, of whom 2040 (26.32%) were pulmonary nodule patients. Older age, current smoking status (hazard ratio (HR) = 1.43, 95% confidence interval (95%CI): 1.21, 1.68), exposure to second-hand smoke (SHS) at work (HR = 1.17, 95%CI: 1.01, 1.35), dust exposure (HR = 1.49, 95%CI: 1.06, 2.11), history of lung disease (HR = 1.44, 95%CI: 1.16, 1.77), and family history of cancer (HR = 1.28, 95%CI: 1.12, 1.48) were associated with pulmonary nodules. However, consumption of vegetables (HR = 0.82, 95%CI: 0.68, 0.99), tea (HR = 0.88, 95%CI: 0.78, 0.99) and legumes reduced the risk. Approximately 10.09% and 8.58% of pulmonary nodule incidences were attributed to tobacco smoking and low fruit intake, respectively. An estimated 6.36% and 3.88% of patients with pulmonary nodules attributable to family history of cancer and history of lung disease were detected. CONCLUSION: The results of this study suggest that age, smoking, SHS, dietary factors, occupational exposures, history of disease and family history of cancer may affect the incidence of pulmonary nodules.

Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma.

Esophageal cancer (EC) is a common malignant tumor of the gastrointestinal tract with a high incidence in China. Zinc (Zn) deficiency is a key risk factor for the occurrence and development of EC and affects progression by regulating microRNA (miRNA, miR) expression. In addition, the dysregulation of miRNAs is accompanied by the dysregulation of their target genes in EC. In this paper, we review the potential molecular mechanisms between Zn deficiency and EC with the aim of providing new strategies and methods for early diagnosis, targeted therapy, and prognostic evaluation.