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The microbiome-gut-brain (MGB) axis, which regulates neurological and cognitive functions, plays an essential role in schizophrenia (SCZ) progression. Dietary inulin could be a novel strategy for the treatment of SCZ due to its modulating effects on the gut microbiota. In this study, the effects of inulin on mice with SCZ were studied. As indicated by the behavioural tests, expression of neurotransmitters, inflammatory indicators, and brain morphology, inulin administration ameliorated aberrant behaviours (locomotor hypoactivity, anxiety disorders and depressive behaviours, and impaired learning and spatial recognition memory) and effectively reduced neuroinflammation and neuronal damage. In addition, inulin improved intestinal integrity and permeability, as indicated by the elevated expression of tight junction proteins (p < 0.05). The results of 16S rRNA sequencing and analysis showed that inulin increased the abundance of Lactobacillus and Bifidobacterium, which were negatively correlated with 5-hydroxytryptamine and inflammatory cytokines and positively correlated with brain-derived neurotrophic factor (BDNF). Inulin caused a reduction in Akkermansia that was positively correlated with inflammatory cytokines and negatively correlated with BDNF. These results suggested that dietary inulin modulated the gut microbiota and exerted anti-inflammatory effects in mice though the MGB axis, which further ameliorated SCZ. Therefore, the results of this study provide a potential explanation for inulin intervention in the treatment of SCZ.

Background In this study, we sought to analyze the clinical outcomes of pharmacomechanical therapy for massive and submassive acute pulmonary embolism (APE). Methods We conducted a retrospective investigation of 97 patients who received pharmacomechanical therapy at out center between January 2013 and June 2018 for acute massive and submassive PE because thrombolysis was contraindicated. Results Of the 97 patients, 46 (47%) were men, and the mean age of the patients was 56 ± 14 years (median, 58 years; range, 21–84 years). Fifty patients had massive PE, whereas the remaining had submassive PE. Analysis of the site of embolus revealed that 67 (69%) had bilateral emboli in the pulmonary arteries (PAs); 5 (5%) only in the left PA, and 25 (26%) only in the right PA. Seventy-nine (81%) of the 97 patients underwent intraoperative placement of the inferior vena caval filters, whereas 3 (3%) required use of a noninvasive ventilator. Two (2%) patients died within 30 days of the interventional therapy because of severe right ventricular failure. The amount of blood loss was nonsignificant. Conclusions Our results indicate that an optimal pharmacomechanical therapy protocol could yield favorable outcomes for rapid clot debulking in cases of massive and submassive APE where thrombolysis is contraindicated. Pending further randomized trials, pharmacomechanical therapy shows promise as an alternative treatment method in cases of acute massive or submassive PE, with minimal risk of major bleeding.

Background: Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) or pulmonary embolism (PE). Not all DVT patients carry the same risk of developing acute pulmonary embolism (APE).Methods: Patients who were diagnosed as symptomatic VTE between June 2013 and June 2018 (n=1582) at the First Affiliated Hospital of Xi’an Jiaotong University were enrolled in this study, of whom 783 had the DVT and APE confirmed by angiography or computed tomography pulmonary angiography (CTPA). Using the LASSO and logistics regression, we derived predictive model with 16 candidate variables to predict the risk of APE and completed internal validation.Results: Overall, 52.9% patients had DVT+APE (773 vs 1460), 47.1% patients only had DVT (687 vs 1460). The APE risk prediction model included one pre-existing disease or condition (respiratory failure), one risk factors(infection), three symptoms (dyspnea, hemoptysis, syncope), five signs (skin cold clammy, tachycardia, diminished respiration, pulmonary rales, accentuation/splitting of P2, tricuspid murmur), and six ECG indicators (SⅠQⅢTⅢ, right axis deviation, left axis deviation, S1S2S3, T wave inversion, Q/q wave), of which all were positively associated with APE. The ROC curves of the model showed AUC of 0.79 (95% CI, 0.77-0.82) and 0.80 (95% CI, 0.76-0.84) in the training set and testing set. The model showed good predictive accuracy (calibration slope, 0.83 and Brier score, 0.18).Conclusion: Based on a retrospective single-center population study, we developed a novel prediction model to identify patients with different risks for APE in DVT patients, which may be useful for quickly estimating the probability of APE before obtaining definitive test results and speeding up emergency management processes.

We analysed lncRNA expression profiles in atrial samples from patients with rheumatic mitral valve disease (RMVD) to identify the potential differences in atrial fibrillation (AF)-associated lncRNAs between RMVD patients with AF and sinus rhythm (SR).Masson's trichrome staining and scanning electron microscopy were performed to evaluate the tissue morphology. Western blotting was performed to detect the expression of fibrosis-related proteins. Difference analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene co-expression networks were also adopted to perform IncRNA expression profile analysis in atrial samples.Masson's trichrome staining indicated higher contents of fat deposition and fibrous tissue in atrial samples from patients with AF than from patients with SR. Western blotting showed that fibrosis-related proteins, including smad2, TGFβ1, MMP9, and TIMP1, were upregulated in atrial samples from patients with AF compared to those from patients with SR. lncRNA expression profiles showed different lncRNA expression levels between RMVD patients with AF and SR. Moreover, GO, KEGG and gene co-expression networks showed consistent results and indicated that differentially expressed genes might contribute to the pathogenesis of AF.Our results revealed the potential roles of IncRNAs in the development of AF in patients with RMVD, and lncRNAs may be responsible for morphological and physiological differences in atria between RMVD patients with AF and SR.

The reduced expression and function of voltage-dependent potassium (KV) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of KV channels is of therapeutic significance for pulmonary hypertension. Beraprost sodium (BPS) has been shown to be effective in patients with pulmonary hypertension. However, the effect of BPS on O2-sensitive KV channels in pulmonary artery smooth muscle cells (PASMCs) remains unclear. In the present study, the effect of BPS on rats with HPH was observed, and the influence of BPS on the expression and function of O2-sensitive KV channels in PASMCs was investigated. The results revealed that BPS reduced mean pulmonary artery pressure, suppressed right ventricular hypertrophy, and attenuated the remodeling of pulmonary arteries in rats exposed to discontinuous hypoxia for 4 weeks (8 h/day). This was accompanied with the significantly upregulated expression of KV channel α-subunits (KV1.2, KV1.5 and KV2.1) and O2-sensitive voltage-gated K+ (KV) channel current (IK(V)) in small pulmonary arteries in HPH model rats, as well as in hypoxia-induced PASMCs. Furthermore, in vitrostudies have revealed that the upregulation of BPS on O2-sensitive KV channels was significantly inhibited after treatment with prostaglandin E2 receptor subtype EP4 antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O2-sensitive KV channels, which was probably via the EP4 receptor-related pathway.

Background: In rural regions of West China, there was almost no intervention on dyslipidemias and abnormal glucose metabolism of individuals with hypertension because of no literature reporting the lipid profile or blood glucose of these patients. This study was designed to investigate the lipid profile and blood glucose level of the hypertensive population in these regions. Methods: A cross-sectional community survey was carried out in Xunyi county of Shaanxi province in West China. The study enrolled 1425 hypertensive patients. The lipid profile and blood glucose levels were assessed. Diet and physical activity were also investigated by questionnaire. Results: 54% of the population had dyslipidemias. The hypercholesterolemia (hyper-TC) and hypertriglyceridemia (hyper-TG) were the main dyslipidemias (hyper-TC:25%; hyper-TG: 33% ). The prevalence of abnormal glucose metabolism was 37%. 16% of the population had hyperglycemia. Despite of low-fat intake, the diet was unbalanced by excess salt consumption and seriously insufficient intake of vegetables, fruits and protein. Conclusion: Dyslipidemias and abnormal glucose metabolism were common in the hypertensive patients in rural areas of West China. They were needed to be invented to reduce the risks of atherosclerotic cardiovascular diseases of hypertensive patients in these regions. Unbalanced diet here may be needed to be modified.

Cerebral small vessel disease (SVD) refers to a heterogeneous group of pathological processes that result from damage to the small penetrating vessels in the brain. Spatial navigation, one of the most fundamental behaviors, has lately attracted considerable clinical interest. This study aimed to determine whether spatial navigation performance is impaired in elderly SVD patients. In total, 18 elderly patients with severe SVD, 40 elderly patients with non-severe SVD, and 41 age-matched healthy volunteers were classified according to the Fazekas scale. Spatial navigation was evaluated by Amunet (a computer-based analogy of Morris water maze software), and a mini-mental scale evaluation (MMSE), animal category verbal fluency test (VFT), clock drawing test (CDT), and trail making test (TMT) -B were also applied. Compared to healthy controls, severe SVD, rather than non-severe SVD patients, exhibited significantly worse performance on “allocentric + egocentric” (41.74 ± 29.10 vs. 31.50 ± 16.47 vs. 29.21 ± 19.03; p = 0.031). Furthermore, the different abilities of spatial navigation among groups reached a statistical level on allocentric subtests (46.93 ± 31.27 vs. 43.69 ± 23.95 vs. 28.56 ± 16.38; p = 0.003), but not on egocentric subtest (56.16 ± 39.85 vs. 56.00 ± 28.81 vs. 43.06 ± 25.07; p = 0.105). The linear regression analysis revealed that allocentric navigation deficit was significantly correlated with TMT-B (p = 0.000, standardized β = 0.342) and VFT (p = 0.016, standardized β = −0.873) performance in elderly SVD patients. These results elucidated that spatial navigation ability could be a manifestation of cognitive deficits in elderly patients with SVD.

Although clinical treatment has significant progress, acute pulmonary embolism is still a common disease with high morbidity and mortality. Janus Kinase 3, a member of JAK family, has been demonstrated to promote smooth muscle cell proliferation through STAT3. In this work, we explored the effect of JANEX-1 (a specific Janus Kinase 3 inhibitor) on platelet-derived growth factor (PDGF)-induced proliferation-related molecules in pulmonary artery smooth muscle cells (PVSMCs) in vitro and assessed the therapeutic potential of Janus Kinase 3 for vascular remodeling in acute pulmonary embolism mice. The results revealed that Janus Kinase 3 was overexpressed and active in PDGF-induced PVSMCs and acute pulmonary embolism mice, compared to a low expression in normal conditions. JANEX-1, blocking Janus Kinase 3 expression or activity, reduced Janus Kinase 3/STAT3 signaling pathway, VEGF expression, FAK activation, and PDGF-induced proliferation of PVSMCs, while overexpression of VEGF or FAK induced PVSMCs proliferation and resisted the negative effects of JANEX-1. Moreover, JANEX-1 improved right ventricular systolic pressure, survival and lung damage in acute pulmonary embolism-mice, and inhibited the thrombus-induced intimal hyperplasia and the expression of α-SMA, VEGF, and FAK activation under neointimal smooth muscle cells of acute pulmonary embolism mice. In conclusion, the data suggest that JANEX-1 exerts protective effects by inhibiting PVSMCs proliferation and vascular remodeling post-acute pulmonary embolism, in part through Janus Kinase 3/STAT3 signaling pathway-mediated VEGF expression and FAK activation. The data are helpful to elucidate the pharmacological mechanism and potential therapeutic effect of JANEX-1 in APE.Impact statementAccumulating evidence suggests that vascular remodeling due to immoderate proliferation and migration of SMCs is a common process occurring in APE. In this work, we tried to find a breakthrough in the pathological mechanism to alleviate the prognosis of APE by improving SMCs proliferation and explored the effect of JANEX-1 on PDGF-induced proliferation-related molecules in PVSMCs and assessed the therapeutic potential of JAK3 for vascular remodeling in APE mice. We demonstrated that JANEX-1, blocking JAK3 expression or activity, reduced JAK3/STAT3 signaling pathway, VEGF expression and FAK activation, and PDGF-induced proliferation of PVSMCs. Moreover, JANEX-1 inhibited the thrombus-induced intimal hyperplasia and the expression of VEGF and FAK activation in neointimal SMCs of APE mice. The data are helpful to elucidate the pharmacological mechanism and potential therapeutic effect of JANEX-1 in APE.

Background May-Thurner syndrome (MTS) or Cockett’s syndrome is a rare clinical syndrome, which refers to the compression of the left common iliac vein (LCIV) by right common iliac artery and vertebral body. Complications of MTS include deep vein thrombus formation and even life-threatening pulmonary embolism. Case presentation Here, we report the case of a 60-year-old female patient with a complaint of swelling in the left lower limb and pain for 5 days. Computed tomography angiography indicated MTS, and thrombus formation of left external iliac vein and femoral vein. The patient was diagnosed with deep venous thrombosis (DVT) and MTS. The patient underwent ascending venography from the lower extremity to inferior vena cava (IVC) and then to the pulmonary artery with IVC filter implantation, left iliac vein balloon plasty, and stent placement. The patient visited the hospital for the removal of IVC filter, 28 days after the operation. After the interventional therapy, the patient had no in-stent restenosis and had remission during the 2-year follow-up. Conclusions This case presents a successful management of MTS in presence of DVT. Although clinicians are rarely aware, the presence of unilateral lower limb swelling and thrombosis may be the manifestations of MTS.

Acute pulmonary embolism (APE) is a common cause of acute cardiovascular failure and has a high morbidity and mortality rate. Inhibiting the excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is a potential treatment strategy following an APE. Various microRNAs (miRNAs/miRs) have been shown to regulate cell proliferation, apoptosis and other physiological processes. However, the specific mechanisms underlying the action of multiple miRNAs are still not understood in APE. In the present study, the role of miR‑106b‑5p on APE was demonstrated in platelet‑derived growth factor (PDGF)‑induced PASMCs in vitro and in an APE‑mouse model in vivo. The results showed that miR‑106b‑5p expression was downregulated in PDGF‑induced PASMCs and APE mice, and NOR1 levels were upregulated. Proliferating cell nuclear antigen (PCNA) expression levels in cells and proliferation of PASMCs proliferation and migration were reduced following treatment with miR‑106b‑5p agomiR, and increased following treatment with miR‑106b‑5p antagomiR. miR‑106b‑5p targeted the 3' untranslated region of NOR‑1 mRNA and reduced NOR1 expression. NOR1 overexpression reversed the effects of miR‑106‑5p on PDGF‑induced PASMCs. The functional roles of miR‑106b‑5p in PDGF‑induced PASMCs and an APE mouse‑model, and the underlying molecular mechanisms were evaluated. AgomiR‑106b‑5p improved APE‑induced mortality and pulmonary vascular proliferation in mice. These data suggest that miR‑106‑5p is a novel regulator of proliferation of PASMCs and of pulmonary vascular remodeling through PDGF‑induced PASMCs in an APE mouse model via targeting NOR1. These results expand the understanding of the pathogenesis underlying APE and highlight potential novel therapeutic targets.

Deep vein thrombosis (DVT) is a common peripheral vascular disease, which may result in pulmonary embolism and is accompanied by endothelial injury. However, the pathogenesis of DVT remains unclear. Coagulation factor XII (FXII), as an important coagulation factor, has been reported to be closely associated with thrombosis. However, the association between FXII protein and DVT formation is not yet fully understood. The present study examined the effects of FXII protein on DVT formation and aimed to reveal the underlying mechanism. In the present study, histological characterization of the femoral vein tissue was examined by hematoxylin and eosin staining. The damage to the femoral vein tissue was examined by TUNEL assay. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were examined using ELISA. Tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑8 and phosphoinositide 3‑kinase (PI3K)/AKT signaling were determined by ELISA, immunohistochemical staining and western blot analysis. The results demonstrated that thrombosis, FXII protein, cell apoptosis and the SOD concentrations were decreased, while the MDA concentrations were increased in mice with DVT compared with the control or sham groups. TNF‑α, IL‑6, IL‑8 and PI3K/AKT signaling was also upregulated in the mice with DVT. Furthermore, the knockdown of FXII significantly upregulated the SOD concentrations and downregulated thrombosis and cell apoptosis, as well as the MDA concentrations in mice with DVT. The knockdown of FXII also significantly downregulated the protein expression of TNF‑α, IL‑6 and IL‑8, and the activation of PI3K/AKT signaling. Additionally, LY294002 pre‑treatment markedly downregulated thrombosis and cell apoptosis and the MDA content, whereas it upregulated the SOD concentrations in mice with DVT. LY294002 pre‑treatment also significantly downregulated the TNF‑α, IL‑6 and IL‑8 protein levels. Taken together, the present study demonstrates that FXII protein promotes DVT via the activation of PI3K/AKT signaling by inducing an inflammatory response. Targeting FXII protein may thus prove to be a potential approach for the treatment of DVT.

Background: To investigate the expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in renal ischemia-reperfusion injury and explore its role in acute kidney injury. Methods: 18 mice were randomly divided into a sham operation group (Sham) and an ischemia-reperfusion group (IR) in which animals were sacrificed at 6 h or 12 h after surgery. The kidneys were harvested to measure the expression of MALAT1 mRNA. HK2 cells were treated with cobalt chloride (CoCl2) to mimic hypoxia or transfected with siRNA to knockdown MALAT1 before CoCl2 treatment. After that, MALAT1 was analyzed by RT-PCR (reverse transcription-polymerase chain reaction). HIF-1ɑ (hypoxia-inducible factor-1 alpha) and NF-κB (nuclear factor-kappa B) was measured by Western blot. The concentrations of IL-6 (interleukin-6) and TNF-ɑ (tumor necrosis factor-alpha) in the media were detected by ELISA (enzyme-linked immunosorbent assay). Results: The expression of MALAT1 in the IR (6 h/12 h) group was significantly higher than that in the sham group. In HK2 cells, MALAT1 was significantly increased at 1 h, 3 h, and 6 h after CoCl2 treatment but had reduced to the basal level at 12 h and 24 h. Knockdown of MALAT1 by siRNA significantly up-regulated the expression of HIF-1ɑ and NF-κB proteins in CoCl2-treated HK2 cells. In addition, the concentrations of IL-6 and TNF-ɑ were increased by MALAT1 siRNA transfection in CoCl2-treated HK2 cells. Conclusion: The expression of MALAT1 is increased in renal ischemia-reperfusion injury. It is likely that MALAT1 inhibits the hypoxia-induced inflammatory response through the NF-κB pathway.

Background Role of plasma vitamin D and genetic variants of its receptor (VDR) in susceptibility to different diseases has been documented. Various studies in different populations have been highlighted strong associations with diabetes and cardiovascular diseases. Vitamin D deficiency has been linked with the development of type 2 diabetes (T2D) and the onset of coronary artery diseases (CAD). However, the role of vitamin D in predisposition to CAD in patients with T2D is ill-defined. Materials and methods We enrolled 674 Chinese T2D patients, and based on clinical phenotype, patients were further categorized into patients with (n = 138) or without coronary artery disease (n = 536). Five hundred twenty-one healthy subjects from similar geographical areas, free from diabetic or coronary disorders, were enrolled as controls. Serum levels of 25-OH vitamin D were quantified by ELISA. Common VDR (FokI, TaqI, BsmI, and ApaI) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Patients with T2D displayed lower levels of 25-OH vitamin D compared with healthy controls. Furthermore, T2D patients with CAD clinical phenotype had the lowest levels of vitamin D. Prevalence of FokI and TaqI mutants was significantly higher in diabetic patients when compared to controls. Interestingly, Tt genotype was more frequent in the artery disease group in comparison with T2D patients without heart involvement. Combined analysis of VDR polymorphisms and serum levels of vitamin D revealed a significant role in predisposition to T2D with or without CAD. Conclusions Lower vitamin D levels and variants of VDR polymorphisms (FokI and TaqI) are associated with susceptibility to T2D and clinical manifestation.

Hui Cheng,1,* Hui Dong,1,* Jianlin Feng,2 Hongyan Tian,1 Haixia Zhang,3 Lina Xu4 1Department of Pathology, The People’s Hospital of Shouguang, Weifang 262700, China; 2Department of Radiology, The People’s Hospital of Shouguang, Weifang 262700, China; 3Department of Radiotherapy, The People’s Hospital of Shouguang, Weifang 262700, China; 4Department of Respiratory Medicine, The People’s Hospital of Weifang, Weifang 262700, China *These authors contributed equally to this work Purpose: This article aimed to investigate the effect of miR-497 on thyroid papillary carcinoma. Materials and methods: miR-497 expression was analyzed using The Cancer Genome Atlas. A total of 56 papillary thyroid carcinoma patients’ tumor tissues and normal tissues were collected. Nthy-ori 3-1 and K1 cells were cultured. K1 cells were also transfected. Quantitative real-time polymerase chain reaction and Western blot were used to detect miR-497 and yes-associated protein 1 (YAP1) expression. Luciferase reporter assay was performed. MTT and Transwell assay were conducted to measure cells’ proliferation, migration and invasion. Immunofluorescence detection was used to detect YAP1-positive cells. Results: miR-497 was downregulated, while YAP1 was upregulated in thyroid papillary carcinoma tissues and K1 cells (P

Pyroptosis is a type of programmed cell death, which has been associated with multiple inflammatory diseases including diabetic atherosclerosis (DA). This study aims to explore the role of sinapic acid (SA) in the pyroptosis of macrophages in DA. Our results from the in vivo experiments showed that low-dose (≤50 mg/kg) chronic SA administration suppressed serum endothelin 1 (ET-1) and interleukin-1β (IL-1β) contents, pyroptotic death of bone marrow-derived macrophages, and the expression of pyroptotic proteins ASC, NRLP3, and caspase-1. Besides, lncRNA-metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was robustly upregulated in the macrophages of rats with DA and could be lowered by low-dose SA administration. Gene overexpression and knockdown experiments showed that MALAT1 had a modestly positive effect on the pyroptosis of normal macrophages. Moreover, in macrophages incubated with high-glucose and Ox-LDL, 1-μM SA treatment displayed a suppressive effect on the cell pyroptosis similar to that of MALAT1 knockdown. Transfection of the pcDNA-MALAT1 expression vector counteracted the decrease in MALAT1 expression and macrophage pyroptosis caused by SA. In conclusion, low-dose SA can abate the pyroptosis of macrophages by downregulation of lncRNA-MALAT1 in rats with DA.

The anti-apoptotic BCL2 family of proteins elicits a broad cell survival program mainly by promoting cell migration, invasion, and metastasis. High expression level of BCL2 family proteins is a characteristic feature of cancer cells, especially in cisplatin-resistant cancer cells. Recent studies have shown that BCL2 family proteins play a housekeeping role in modulating mitochondrial dynamics. However, it is not clear whether BCL2 family proteins are relevant to mitochondrial fission and fusion in cisplatin-resistant ovarian cancer cells. Here, we report that the BCL2/BCLXL inhibitor ABT737 induced apoptosis more potently in cisplatin-resistant SKOV3/DDP ovarian cancer cells than in cisplatin-sensitive SKOV3 ovarian cancer cells. ABT737 significantly increased levels of DRP1 in mitochondria and increased rates of mitochondrial fission, and then induced cytochrome C release from mitochondria and mitophagy in SKOV3/DDP cells. Mdivi-1, a selective inhibitor of DRP1, weakened ABT737-induced mitochondrial fission, intrinsic apoptotic pathways, and mitophagy in SKOV3/DDP cells. Taken together, these results demonstrate a novel function of ABT737 in inducing DRP1-dependent apoptotic mitochondrial fission and highlight that targeting anti-apoptotic BCL2 family proteins may be an emerging therapeutic strategy for patients with cisplatin-resistant ovarian cancer.

The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p‑p53‑Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer.

Objective: To explore the impact of different educational models on disease recognition and compliance in patients with type 2 diabetes. Methods: For 100 patients with type 2 diabetes who were filed at the Changyanbao Community Health Service Center and the Electronic City Community Health Service Center from January 2017 to January 2018, the patients with diabetes were divided into 50 patients in the patient education group (group I) and 50 patients in the comprehensive education group (group II) according to the order of establishment. Observe the effects of different educational models on disease recognition and compliance in patients with type 2 diabetes. Results: After the relevant education, the effects of disease recognition and compliance were significantly higher in both groups (P

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Background: The purpose of this study is to elucidate mechanism(s) by which the orally active PGI2 analog, Beraprost (BPS), ameliorates pulmonary hypertension (PH). Prostaglandins are an important treatment for PH. Mechanisms of their action are not fully elucidated in relation to receptor subtype and effects on O2 sensitive Kv channels. Methods: Distal (3rd order and beyond) pulmonary arteries from chronically hypoxic rats and from humans with established PH were studied. Measurements included pulmonary haemodynamics and histology, vascular reactivity, prostanoid receptor expression and activity of the O2 sensitive Kv channels. Results: Prostacyclin receptor (IP), prostaglandin receptor E3 (EP3) and prostaglandin receptor E4 (EP4) are the main pulmonary artery receptor subtypes in both rat and human pulmonary arteries. Circulating levels of PGI2 and PGE2 were reduced in PH. PH was also associated with reduced receptor expression of IP but not of EP4. The effects on IP expression were overcome with BPS. Dilatory responses in PH to BPS were reduced in the presence of EP4 blockade. Expression and activity of oxygen sensitive Kv channels were reduced in pulmonary artery smooth muscle cell from rats with PH and humans with PAH and were also overcome by administration of BPS. Effects of BPS on oxygen sensitive Kv channels were reduced in the presence of EP4 blockade implicating the EP4 receptor, as well as the IP receptor, in mediating BPS effects. Conclusion: Reduced expression of pulmonary IP receptors and reduced activity of O2 sensitive Kv channels are found in PH in both humans and rats. The orally active prostacyclin analogue, BPS, is able to reverse these changes, partly through binding to the EP4 receptor.

The building of a beautiful Zhejiang and the creation of a good life need to be guaranteed by a beautiful economy including beautiful ecological industries and beautiful green consumption. As a province which met with the growing pains at the earliest, Zhejiang has the deepest understanding of the important significance of the transformation of the developmental mode and economic transformation and upgrading, so under the guidance of the developmental outlook through which clean, clear waters and lush mountains are the “gold and silver mountains”, Zhejiang has vigorously promoted the transformation from a black economy to a green economy, from a linear economy to a circular economy, from a high-carbon economy to a low-carbon economy, and it has made gratifying achievements in this regard, preliminarily demonstrating the charm of a conservation-oriented and environmentally friendly economy and providing the model for national economic transformation and upgrading.

MicroRNA (miRNA) is associated with the development and pathology of atrial fibrillation (AF). In this study, we performed miRNA profiling of left and right atrium samples from individuals with AF-associated rheumatic mitral valve disease (RMVD) to identify miRNAs that are differentially expressed between RMVD patients with AF and RMVD with sinus rhythm (SR) as controls, as well as between left and right atrium samples from RMVD with AF patients. We performed hematoxylin and eosin staining as well as scanning and transmission electron microscopy to examine in detail any morphological and physiological changes in cardiomyocytes from RMVD patients with AF or SR. Raman spectroscopy was performed to identify molecular and structural information of left and right atrium samples from RMVD with AF and SR. We also performed miRNA array profiling to separately profile miRNA expression patterns of right and left atrium samples from three independent RMVD patients with AF and in a mixed pool of 10 RMVD patients with SR. Morphological and physiological analysis showed distinct shapes and structures of cardiomyocytes from the left and right atria of RMVD patients with AF or SR. The intensity of Raman spectroscopy of atrial tissues from RMVD patients with AF and with SR was different. miRNA profiling showed differential miRNA expression between RMVD patients with AF or SR, and between the left and right atria of RMVD patients with AF. Importantly, miRNAs showed consistent expression changes among all three patients, suggesting that these miRNAs have potential as markers for AF pathology. Our results revealed potential biomarker miRNAs for atrial fibrillation pathology in patients with RMVD. Meanwhile, our data suggested that miR-10b and miR-138-2, which were both significantly increased in the left atrium, are responsible for morphological and physiological phenotype differences between the left and right atria.

To investigate whether resistin is associated with early atherosclerosis in male smokers. The present study consecutively enrolled 50 male smokers. Their serum resistin contents were detected with enzyme linked immunosorbent assay (ELISA), and subclinical atherosclerosis indices, including carotid inner middle thickness (IMT) and arterial elasticity indices (C1 and C2), were measured. The association between serum resistin levels and IMT, C1 and C2 were respectively evaluated with the Pearson's correlation coefficient method. The results showed that the serum resistin level had a positive association with IMT (r = 0.307, p = .030), but were both inversely associated with C1 (r = -0.440, p = .001) and C2 (r = -0.381, p = .006). These associations remained significant even after adjustment for cardiovascular confounders. In conclusion, serum resistin concentration was independently associated with early atherosclerosis in male smokers.

Objective It has been confirmed that adipokines are associated with atherosclerosis. Cigarette smoking was found to possibly influence adipokine secretion. However, the precise role of smoking in adipokine secretion and the underlying mechanisms are largely unknown. The aim of this study was to determine whether nicotine, the principal active ingredient of cigarettes, can influence adipokine secretion and its potential mechanism. Methods The present study consecutively enrolled 96 men, including 50 smokers with early atherosclerosis and 46 nonsmokers. Serum adipokines, including leptin, resistin, and visfatin, were determined with enzyme-linked immunosorbent assay in all participants. Furthermore, the effect of nicotine on secretion of these adipokines was examined in differentiated 3T3-L1 preadipocytes under the conditions of ATP-dependent potassium (KATP) channel blocked or unblocked. Results Compared with the control group, serum levels of leptin, resistin, and visfatin in smokers were significantly higher. In 3T3-L1 adipocytes, nicotine treatment significantly increased the levels of these adipokines ( P = 0.014, 0.001, and 0.029, respectively). When the KATP channel was blocked, secretion of resistin and visfatin was reduced ( P P = 0.522). Conclusions Nicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel.

Pulmonary arterial hypertension (PAH) is a syndrome caused by restricted blood flow in the pulmonary circulation, which results in a poor patient prognosis. The serotonin (5-HT), TRPC1 (Transient receptor potencial channel 1), TRPC6 (Transient receptor potencial channel 6), calcineurin A, and NFATc3 (an isoform of nuclear factor of activated T-cells family) are involved in cell proliferation and hypertrophy and the crosstalk between these molecules may play an essential role in the pathogenesis of pulmonary arterial hypertension. We hypothesized that 5-HT promotes PAH by affecting TRPC channels. We investigated the effects of sarpogrelate, a 5-HT2A receptor antagonist, on pulmonary arterial pressure, cardiac remodeling, pulmonary artery remodeling, and TRPC1, TRPC6, calcineurin A, and NFATc3 expression in pulmonary arteries from rats with PAH. The results showed that sarpogrelate reduced pulmonary arterial pressure, cardiac remodeling, pulmonary artery remodeling, and expression of TRPC1, TRPC6, calcineurin A, and NFATc3 in pulmonary arteries. In conclusion, Sarpogrelate reduced the severity of PAH in rat model and decreased the expression of TRPC1, TRPC6, calcineurin A, and NFATc3 in pulmonary arteries.

Natural marine products are useful candidates for the treatment of oxidative and inflammatory diseases, including myocardial ischemia. 3-bromo-4,5 - dihydroxybenzaldehyde (BDB), a natural bromophenol isolated from marine red algae, has been shown to display anti-microbial, anti-oxidative, anti-cancer, anti-inflammatory, and free radical scavenging activities. In this study, the potential protective effects of BDB against myocardial ischemia and reperfusion (IR) injury was investigated in an in vitro model mimicked by oxygen and glucose deprivation (OGD) in cardiomyocytes and in an in vivo model induced by coronary artery ligation in rats. The results showed that BDB attenuated the OGD-induced cytotoxicity in a dose-dependent manner, with no toxic effect when treated alone. BDB significantly decreased apoptosis and the cleavage of caspase-3 after OGD. We found that OGD-induced oxidative stress, as evidenced by increases of reactive oxygen species (ROS) and lipid peroxidation, as well as mitochondrial dysfunction, as measured by mitochondrial reporter gene, cytochrome c release and ATP synthesis, were markedly attenuated by BDB treatment. In addition, BDB increased the enzymatic activities of mitochondrial antioxidant enzymes, including IDH2, GSH-Px and SOD2. Western blot analysis showed that BDB increased Akt phosphorylation and upregulated the expression of Sirt3 and PGC1α after OGD. Furthermore, BDB-induced protection in cardiomyocytes was partially reversed by the Akt inhibitor and downregulation of PGC1α. BDB also attenuated myocardial contractile dysfunction and activated the Akt-PGC1α-Sirt3 pathway in vivo. All these data suggest that BDB protects against myocardial IR injury through activating the Akt-PGC1α-Sirt3 pathway.

The current study aimed to investigate the effects of sildenafil and N-acetylcysteine (NAC) on the haemodynamics in a rabbit model of acute pulmonary thromboembolism (APT). We developed an APT model using healthy male China big-ear rabbits (2.7 ± 0.4 kg). The rabbits were divided into five groups subjected to various interventions. We recorded the haemodynamic parameters and assessed the oxidative stress and lipid peroxidation response in the groups. Additionally, we detected apoptosis-associated molecules, FoxO1, Bad and Bcl-2, in the lung tissue. Gelatine zymography was used to detect matrix metalloproteinase (MMP) activity in bronchoalveolar lavage (BLA). Pulmonary artery endothelial cells were isolated, and their apoptosis rates and MMP activity were assayed. N-acetylcysteine potentiated the haemodynamic-improving effect of sildenafil and significantly inhibited the oxidative stress response. N-acetylcysteine combined with sildenafil decreased MMP-2 and MMP-9 activity and NO consumption and inhibited apoptosis of pulmonary arterial endothelial cells. Moreover, NAC combined with sildenafil inhibited the expression of MCP-1 and p-p38 MAPK. Thus, NAC potentiates the haemodynamic-improving effect of sildenafil in a rabbit model of acute pulmonary thromboembolism via the MCP-1 and p38 MAPK signalling pathway. This study may provide a promising treatment method for APT.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Pulmonary arterial remodeling is characterized by excessive proliferation, migration, and pro-differentiation and fibrotic activation of adventitial fibroblasts in pulmonary arterial hypertension (PAH) process. Several lines of evidence indicate that serotonin (5-HT) plays a central role in the pathogenesis of pulmonary arterial remodeling. In the present study, we investigated whether 5-HT is directly involved in the functional regulation of pulmonary artery adventitial fibroblasts (PAFs). Incubation of cultured rat PAFs with 5-HT caused a dose-dependent stimulation of cell proliferation, migration activity, and a time-dependent increase of α-SMA expression, a marker of fibroblast differentiation into myofibroblasts, and adventitia fibrosis, evaluating connective tissue growth factor (CTGF) and extracellular matrix (ECM) mRNAs and proteins. These effects were attenuated by the 5-HT2A receptor antagonist, ketanserin and mimicked by the 5-HT2A receptor agonist DOI. 5-HT-induced fibroblasts phenotypic alterations and ECM accumulation were dependent on stimulation of transforming growth factor (TGF)-β1 as demonstrated using a neutralizing antibody. 5-HT also caused Smad3 phosphorylation and ketanserin diminished 5-HT-induced Smad3 activation. These results demonstrated that 5-HT can directly activate PAFs through 5-HT2A receptor and promote fibroblasts phenotypic alterations and adventitia fibrosis depending on the signaling of the TGF-β1/Smad3 pathway.

The article appeared in GenesGenetic Systems Vol. 94, No. 1 (p. 23-34) was listed under the incorrect category. We apologize for this error. The correction is as follows: Incorrect: Mini review Identification of atrial fibrillation-associated microRNAs in left and right atria of rheumatic mitral valve disease patients Yang Yan, Rui Shi, Xiaojiang Yu, Chaofeng Sun, Weijin Zang and Hongyan Tian Correct: Full paper Identification of atrial fibrillation-associated microRNAs in left and right atria of rheumatic mitral valve disease patients Yang Yan, Rui Shi, Xiaojiang Yu, Chaofeng Sun, Weijin Zang and Hongyan Tian.

Decreased pulmonary artery smooth muscle cell (PASMC) apoptosis play a key role in pulmonary artery remodeling during pulmonary artery hypertension (PAH), but the mechanisms involved are unclear. Serotonin (5-HT) inhibits apoptosis in many pathologic processes by activating the 5-HT2A receptor. Therefore, we hypothesized that 5-HT may be the promoter of decreased apoptosis in PAH through the 5-HT2A receptor. We found that inhibition of the 5-HT2A receptor prevented the increase in pulmonary artery pressure and pulmonary artery remodeling in rats stimulated by monocrotaline. This effect was accompanied by increased apoptosis in the pulmonary artery. Cultured PASMCs stimulated with 5-HT showed a decrease in apoptosis with increased phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), pyruvate dehydrogenase kinase (PDK), and mitochondrial transmembrane potential. These effects were markedly prevented by a 5-HT2A receptor inhibitor, an ERK1/2 activation inhibitor peptide I, or a PDK inhibitor. In conclusion, 5-HT inhibited PASMC apoptosis by activating the 5-HT2A receptor through the pERK1/2 and PDK pathways.5-HT decreasing apoptosis through 5-HT2A receptor is involved, at least in part, in pulmonary artery remolding.

Angiotensin II (AngII) is the most important component of angiotensin, which has been regarded as a major contributor to the incidence of hypertension and vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6 (CTRP6) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP6 in the progression of AngII induced hypertension and vascular endothelial function remains unclear. Here, we showed that serum CTRP6 content was significantly downregulated in SHRs, accompanied by a marked increase in arterial systolic pressure and serum AngII, CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII expression and AngII-mediated hypertension and vascular endothelial inflammation. In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression. Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2 signaling pathway and the expression of peroxisome proliferator-activated receptor γ (PPARγ), a recently proven negative regulator of AngII, in the brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in endothelial cells, and caused a significant increase in PPARγ activation and suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The effect of that could be rescued by the ERK inhibitor PD98059. In contrast, silencing CTRP6 suppressed PPARγ activation and exacerbated AngII-mediated vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves PPARγ activation and alleviates AngII-induced hypertension and vascular endothelial dysfunction.

This study investigated whether sarpogrelate hydrochloride (SPG), a 5-HT2A receptor antagonist, alleviates chronic hypoxic pulmonary hypertension (CH-PH) in rats by stimulating apoptosis and inhibiting proliferation in pulmonary artery smooth muscle cells (PASMCs).Forty male Sprague-Dawley rats were pretreated with SPG (50 mg/kg/day by oral gavage) or saline vehicle and then subjected to chronic hypoxia (CH) (hypobaric chamber set to 380 mmHg, 10% oxygen) or normoxia for 14 days. Mean pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH) were measured. Hypertensive pulmonary vascular remodeling was assayed by light microscopy. Terminal deoxynucletidyl transferase dUTP nick end ligase (TUNEL) assays, western blotting, and real-time polymerase chain reaction were used to assess apoptosis, proliferation and underlying signaling pathways in PASMCs from lung tissue and isolated pulmonary artery rings.CH increased mean PAP and RVH. CH increased the percentage of muscularized arteries in the peripheral pulmonary vasculature and medial wall thickness in small muscular arteries. CH increased pulmonary protein and mRNA levels of the B-cell lymphoma protein 2 (Bcl-2), pyruvate dehydrogenase kinase (PDK), phosphorylation of extracellular signal-regulated kinases 1 and 2 (pERK1/2), cyclin D1, proliferating cell nuclear antigen (PCNA) and decreased protein and mRNA levels of Bcl-2-associated X protein (BAX), cleaved caspase-3. Pretreatment with SPG, which has been shown previously to inhibit ERK1/2 phosphorylation and PDK, countered all of these effects. Isolated pulmonary artery rings incubated with 5-HT increased pERK1/2, PDK, and Bcl-2 expression, and decreased Bax expression.Administration of SPG ameliorated the development of CH-PH by stimulating apoptosis in and inhibiting proliferation of PASMCs.

Background MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors. However, the expression and the role of miR-138 in human osteosarcoma are still poorly understood. We investigated the function and the underlying mechanism of miR-138 in osteosarcoma. Methods The expression of miR-138 in human osteosarcoma tissues and cell lines was detected by real-time PCR analysis. The gain-of-function and loss-of-function experiments were performed on osteosarcoma cell lines to investigate the effects of miR-138 on osteosarcoma progression, and to determine whether differentiated embryonic chondrocyte gene 2 (DEC2) mediates these effects. Cell proliferation, apoptosis and invasion were assessed by MTT, flow cytometry and transwell-matrigel assays. Dual-luciferase reporter assay was used to identify whether DEC2 is a direct target of miR-138. Results MiR-138 was significantly downregulated in human osteosarcoma tissues and cell lines. Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues. The in vitro gain-of-function and loss-of-function experiments demonstrated that miR-138 inhibited cell proliferation and invasion, and promoted cell apoptosis of human osteosarcoma cells. DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression. Conclusions These findings suggested that miR-138 acts as a tumor suppressor in osteosarcoma.miR-138 inhibited cell proliferation and invasion, as well as promoted cell apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of DEC2. MiR-138/DEC2 may be a novel therapeutic target in osteosarcoma.

Insulin resistance plays an important role in the development of hypertension, which is seriously detrimental to human health. Recently, Sirtuin-1 (SIRT1) has been found to participate in regulation of insulin resistance. Therefore, further studies focused on the SIRT1 regulators might provide a potential approach for combating insulin resistance and hypertension. Interestingly, in this study, we found that SIRT1 was the target gene of the miR-543 by the Dual-Luciferase Reporter Assay. Moreover, the miR-543 expression notably increased in the insulin-resistant HepG2 cells induced by TNF-α. Further analysis showed that the overexpression of the miR-543 lowered the SIRT1 mRNA and protein levels, resulting in the insulin resistance in the HepG2 cells; the inhibition of miR-543, however, enhanced the mRNA and protein expression of the SIRT1, and alleviated the insulin resistance. Furthermore, the SIRT1 overexpression abrogated the effect of miR-543 on insulin resistance. In addition, the overexpression of the miR-543 by the lentivirus-mediated gene transfer markedly impaired the insulin signaling assessed by the Western blot analysis of the glycogen synthesis and the phosphorylation of Akt and GSK3β. In summary, our study suggested that the downregulation of the miR-543 could alleviate the insulin resistance via the modulation of the SIRT1 expression, which might be a potential new strategy for treating insulin resistance and a promising therapeutic method for hypertension.

Objective: To evaluate the clinical course of patients treated for multiple perforations, complex femoral artery pseudoaneurysms. Methods: Seven patients with multiple perforations, complex pseudoaneurysms after femoral artery access for interventional procedures were treated. Ultrasound-guided thrombin injection (UGTI) was first used for treatment. Patients failing repeated UGTIs were treated with fibrin sealant injections. Results: Five of the seven patients treated with UGTIs had rapid thrombus formation within the pseudoaneurysm. Two patients refractory to UGTI had successful treatment using fibrin sealant injection. There were no complications and the overall cure rate was 100%. Conclusions: Treatment of complex femoral artery pseudoaneurysms is safe and effective. UGTI and fibrin sealant are useful in the treatment of complex pseudoaneurysms.

To assess the comparative safety and efficacy of a new parenteral lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid20%) for postoperative patients, a meta-analysis of randomized controlled trials (RCTs) was conducted. Six RCTs with a total of 306 patients were included in the analysis. The overall quality of evidence for each outcome was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) software. Compared with a soybean-based (Lipoven20%) and a soybean- and olive oil-based (ClinOleic20%) lipid emulsion, SMOFlipid20% was associated with lower levels of hepatic enzymes, suggesting less toxicity. Changes in low-density lipoprotein triglyceride and C-reactive protein levels were also lower with SMOFlipid20% compared with Lipoven20%. Differences between SMOFlipid20% and a lipid emulsion containing medium- and long-chain triglycerides (MCT/LCT20%) were not statistically significant. For all trials, there were no significant differences in adverse events and length of hospital stay. The quality of evidence from the RCTs evaluating SMOF20% versus Lipoven20% was moderate, while most of the evidence from RCTs of SMOF20% versus ClinOleic20% and MCT/LCT20% lipid emulsions was low.

Paradoxical peripheral arterial embolism is an important clinical entity and potentially morbidity-threatening. However, the risk factors of paradoxical peripheral arterial embolism are unclear. We investigated what clinical presentations are likely risk factors for paradoxical peripheral arterial

Abnormally functioning K(+) channels during aging might contribute to increased arterial tone of vascular smooth muscle cells. However, changes in large conductance calcium-activated potassium (BKca) channel current density and channel protein composition during aging are not fully understood and are currently investigated here. Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were grouped by age into very young (4-6 weeks), young (16-18 weeks), and adult (40-42 weeks) rats. BKca current was measured using a whole cell patch clamp in vascular smooth muscle cells from rat mesenteric arteries. BKca channel and subunits were measured using confocal imaging and real-time reverse transcriptase polymerase chain reaction techniques. Systolic and diastolic blood pressure increased significantly with age in both SHR and WKY rats. The expression of BKca α subunits increased in plasma membrane and cytoplasm in both SHR and WKY rats during aging, but had a larger increase in the cytoplasm in SHR than in WKY rats. BKca current density increased with aging in SHR but not in WKY rats. The relative abundance of BKca α and β1 mRNA transcripts changed minimally or not at all with aging in both SHR and WKY rats. In conclusion, plasma membrane BKca protein increased with aging in both SHR and WKY rats. Increases in cytoplasmic BKca protein and in BKca current were greater in SHR than WKY rats.

Background The objective of the present study was to determine the effect of various concentrations of oleic acid (OA) on K ATP channel expression and the potential relationship to exogenous nitrogen monoxide and protein kinase C levels. Methods Human umbilical artery smooth muscle cells (HUASMCs), between the 7th and 10th passages, were divided into control group, OA group (final OA concentration of 0, 50, 100 or 200 μmol/L), nitric oxide (NO) intervention group, protein kinase C inhibitor group or GF-109203X (GFX) intervention group. Western immunoblotting was used to detect the protein expression of the K ATP channel subunit Kir6.1. Also, quantitative real-time polymerase chain reaction analysis to determine Kir6.1 messenger RNA levels and whole-cell patch clamping to measure K ATP currents were performed. Results The results suggested that OA inhibited Kir6.1 protein and messenger RNA expression in HUASMCs. Under a high concentration of potassium (140 mmol/L), 100 μmol/L OA significantly reduced ATP-sensitive potassium current density, whereas a low extracellular concentration of potassium (5.4 mmol/L) did not influence K ATP density. Pretreatment with either exogenous NO or GFX weakened the OA-induced inhibition of K ATP in HUASMCs. Conclusions The study demonstrated that OA inhibited Kir6.1, a K ATP channel subunit, in HUASMCs, and indirectly inhibited the K ATP current. In addition, the results indicated that NO and/or GFX partially reversed OA inhibition in HUASMCs.

Objective: To explore the effects of preoperative administration of conventional doses of atorvastatin plus trimetazidine on the myocardial injury of patients during the perioperative period of percutaneous coronary intervention (PCI). Methodology: 475 cases of acute coronary syndrome patients before PCI were randomly divided into the control group (238 cases) and experimental group (237 cases).The control group was treated with conventional doses of atorvastatin calcium (20 mg each time, once a night), and the experimental group was treated with conventional doses of atorvastatin calcium plus trimetazidine hydrochloride (20 mg each time, tid) for 3 d. After PCI, preoperative and postoperative 24 h concentrations of serum creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP) as well as activity of myeloperoxidase (MPO) were investigated. Left ventricular ejection fractions of the patients were then examined 4 weeks later. Results: Postoperative 24 h cTnI concentration and elevated MPO activity of the experimental group were significantly lower than those of the control group (P 0 05). Conclusion: The administration of conventional doses of atorvastatin plus trimetazidine three days before PCI is able to protect the perioperative patients from myocardial injury.

Electrophysiological properties of implanted mesenchymal stem cells (MSCs) in infarcted hearts remain unclear, and their proarrhythmic effect is still controversial. The intent of this study was to investigate electrophysiological properties and proarrhythmic effects of MSCs in infarcted hearts. Rats were randomly divided into a myocardial infarction (MI) group, a MI-DMEM group (received DMEM medium injection) and MI-MSCs group (received MSCs injection). Survival analysis showed that the majority of engrafted MSCs died at day 9 after transplantation. Engrafted MSCs expressed cardiac markers (MYH, cTnI, Cx43), cardiac ion channel genes (Kv1.4, Kv4.2 and Kir2.1) and potassium currents (I (to), I (K1) and I (KDR)), but did not express Nav1.5, Cav1.2, Na(+) current and Ca(2+) current during their survival. When induced by Ca(2+), implanted MSCs exhibited no contraction ability after being isolated from the heart. Following 8-week electrocardiography monitoring, the cumulative occurrence of ventricular arrhythmias (VAs) was not different among the three groups. However, the prolonged QRS duration in infarcted rats without VAs was significantly decreased in the MI-MSCs group compared with the other two groups. The inducibility of VAs in the MI-MSCs group was much lower than that in the MI and MI-DMEM groups (41.20 vs. 86.67 % and 92.86 %; P 0.0125). The ventricular effective refractory period in MI-MSCs group was prolonged in comparison with that in the MI and MI-DMEM groups (56.0 ± 8.8 vs. 47.7 ± 8.8 ms and 45.7 ± 6.2 ms; P 0.01). These results demonstrate that MSCs do not acquire the electrophysiological properties of mature cardiomyocytes during the survival period in the infarcted hearts. However, they can alleviate the electrical vulnerability and do not promote ventricular arrhythmias.

K ATP channel in vascular smooth muscle cell (VSMC) is closely linked to the etiology of hypertension. The aim of this study was to investigate effect of the high-fat diet-induced obesity on K ATP channel and blood pressure. Obesity was induced by a 24-week high-fat diet feeding in rats. Function and expression of K ATP channel in mesenteric arteries were examined using myography system, patch clamp and Western blotting. We show that high-fat diet increased blood pressure, decreased K ATP channel-mediated relaxation responses and currents, and down-regulated K ATP expression in VSMC. In conclusion, diet-induced obesity impairs K ATP channels in VSMC, which may underscore obesity-triggered increase in blood pressure.

To evaluate the safety and effectiveness of catheter-directed thrombolysis therapy with low-dose urokinase for acute lower extremity ischemia limb. Retrospective analysis of clinical data of 50 cases, including 27 males and 23 females, aged 27-81 years old, the onset time of 10 hours to 14 days