Effect of statin use on risk and mortality of gastric cancer: a meta-analysis.

The effect of statins on gastric cancer risk is still controversial. And studies on the association between statins and gastric cancer mortality are very limited. Therefore, we conducted this systemic review and meta-analysis to evaluate the association between the use of statin and gastric cancer. Searched studies were published before November 2022. Odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using STATA 12.0 software. The study showed that the statin use group showed a significantly lower risk of gastric cancer, compared to no statin use group (OR/RR, 0.74; 95% CI: 0.67-0.80, P  < 0.001). The study showed that the statin use group showed significantly lower all-cause mortality and cancer-specific mortality of gastric cancer, compared to no statin use group (all-cause mortality: HR, 0.70; 95% CI: 0.52-0.95, P  = 0.021; cancer-specific mortality: HR, 0.70; 95% CI: 0.58-0.84, P  < 0.001). Overall, results from this meta-analysis showed the protective effect of statins exposure on the risk and prognosis of gastric cancer; however, we still need more well designed, large-scale studies and randomized clinical trials to pinpoint the effect of statins on gastric cancer in future clinical practice.

Evaluation of Carbon Nanoparticle Suspension and Methylene Blue Localization for Preoperative Localization of Nonpalpable Breast Lesions: A Comparative Study.

Background: The resection of nonpalpable breast lesions (NPBLs) largely depends on the preoperative localization technology. Although several techniques have been used for the guidance of NPBL resection, more comfortable and effective methods are needed. This aim of this study was to evaluate the use and feasibility of carbon nanoparticle suspension (CNS) and methylene blue (MB)-guided resection of NPBL, to introduce alternative techniques. Methods: A total of 105 patients with 172 NPBLs detected by breast ultrasound were randomized to CNS localization (CNSL) group and MB localization (MBL) group. The injection times of the two groups were divided into 2, 4, 6, 12, 16, and 20 h before surgery. In this study, localization time, stained area, operation time, total resection volume (TRV), calculated resection ratio (CRR), and pathological diagnosis were assessed. Results: All of the 172 lesions were finally confirmed benign. Dye persisted in all cases in the CNSL group (109/109, 100%), while that persisted in only 53 cases in the MBL group (53/63, 84.1%) (P < 0.001). There was a significant correlation between dyeing time and dyeing area in the MBL group (r = -0.767, P < 0.001); however, there was no significant correlation in the CNSL group (r = -0.154, P = 0.110). The operation time was 11.05 ± 3.40 min in the CNSL group and 13.48 ± 6.22 min in the MBL group (P < 0.001). The TRV was 2.51 ± 2.42 cm3 in the CNSL group and 3.69 ± 3.24 cm3 in the MBL group (P = 0.016). For CRR, the CNSL group was lower than the MBL group (7.62 ± 0.49 vs. 21.93 ± 78.00, P = 0.018). There is no dye remained on the skin in the MBL group; however, dye persisted in 12 patients (19.4%) in the CNSL group (P = 0.001). Conclusion: Carbon nanoparticle suspension localization and MBL are technically applicable and clinically acceptable procedures for intraoperatively localizing NPBL. Moreover, given the advantages of CNSL compared to MBL, including the ability to perform this technique 5 days before operation and smaller resection volume, it seems to be a more attractive alternative to be used in intraoperative localization of NPBL.

Public mobilisation in implementation of smoke-free Beijing: a social media complaint platform.

In November 2014, Beijing People's Congress adopted the Beijing Smoking Control Ordinance and a key provision bans smoking in all indoor public places, workplaces and on public transport. To ensure effective implementation of the ordinance, the government calls on the whole society to take part. In response, Beijing Tobacco Control Association, with the support of a local technology company, developed the Beijing Tobacco Control Map, a digital system that enables comprehensive tobacco control information collection, data visualisation and mapping. A key component of the Beijing Tobacco Control Map is the Complaint Map which is generated by the data of reported violations of the smoke-free provisions by the general public through a social media platform. The Complaint Map visually displays the reported violations on a map of Beijing in real time. The general public can access the Complaint Map at any time to see which venues and locations have been reported. It is used by tobacco control volunteers, who are recruited and trained to address complaints and promote compliance. It is also used by the government's enforcement team for targeted inspections. The Complaint Map has effectively engaged the public and promoted a smoke-free Beijing. Beijing's innovative and systematic approach that involves the Complaint Map, volunteer management, coordination with the enforcement team, and media exposure can be replicated or adapted in other cities in China and abroad that are implementing smoke-free laws or tobacco control laws in general.

Multivisceral IgG4-related disease presenting as recurrent massive gastrointestinal bleeding: a case report and literature review.

BACKGROUND: IgG4-related disease (IgG4-RD) is a newly recognized autoimmune systemic disorder characterized by elevated levels of serum IgG4 and abundant infiltration of IgG4-positive plasmacytes in the affected organs. The liver, biliary system and pancreas are the most commonly affected organs. However, involvement of the digestive tract is very rare. To date, only a few cases of isolated gastric IgG4-RD have been reported. CASE PRESENTATION: We present a case of IgG4-RD of the liver, gallbladder, pancreas and duodenum, which was clinically misinterpreted and thereafter over-treated. A 52-year-old male presented with obstructive jaundice for 3 years, melena for 5 months and hematemesis for 10 days. Three years prior, the patient had undergone biopsies of pancreatic lesions, liver lesions, cholecystectomy and choledochojejunostomy. Histopathology showed chronic inflammatory changes. Endoscopy at admission revealed a duodenal ulcer with active bleeding. Despite medical management, the patient presented with repeated gastrointestinal bleeding. Upon evaluation, serum IgG4 levels were found to be elevated. Histopathology of the duodenal ulcer biopsy and repeated examination of the gallbladder and pancreatic and liver biopsies confirmed IgG4 positive plasma cell infiltration. A definitive diagnosis of IgG4-RD was made and steroid administration was initiated. At last follow up, 11 months to-the-day after initiating steroid treatment, the patient was asymptomatic. CONCLUSIONS: Notably, IgG4-RD of multiple digestive organs is still very rare. As a systemic disease, it is characterized by the infiltration of IgG4-bearing plasma cells and raised IgG4 levels. Histopathology findings remain the diagnostic gold standard for this disorder.

Cardiac Hypertrophy is Positively Regulated by MicroRNA­24 in Rats

Background: MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Methods: Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and 3H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. Results: The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = -2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. Conclusion: MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression.

AMPK-KLF2 signaling pathway mediates the proangiogenic effect of erythropoietin in endothelial colony-forming cells.

Endothelial colony-forming cells (ECFCs) were proved to take part in postnatal vasculogenesis and injury repair. The angiogenic properties of ECFCs could be influenced by various cytokines, chemokines, and growth factors. Erythropoietin (EPO) is a promising cytokine participating in angiogenesis. However, the mechanisms for EPO's proangiogenic effect still remain largely elusive. Here, we investigated the role of the AMP-activated protein kinase (AMPK)-Krüppel-like factor 2 (KLF2) signaling pathway in the proangiogenic effect of EPO in ECFCs. Human ECFCs were isolated from cord blood and cultured. EPO significantly enhanced the migration and tube formation capacities of ECFCs and markedly increased the expression of endothelial markers and vascular endothelial growth factor (VEGF). Further, EPO caused the phosphorylation of AMPK and endothelial nitric oxide synthase, a process in which KLF2 was also upregulated on both mRNA and protein levels. The upregulation of KLF2 was blocked by inhibiting AMPK with Compound C or Ad-AMPK-DN, a recombinant adenovirus that encoded a dominant-negative mutant of AMPK. Furthermore, knockdown of KLF2 showed no effect on AMPK but abolished the EPO-enhanced migration and tube formation capacities of ECFCs. Of note, knockdown of KLF2 also diminished the EPO-induced expression of endothelial markers and VEGF; overexpression of KLF2 promoted the expression of endothelial markers and VEGF and enhanced the migration and tube formation capacities of ECFCs. These data suggest that upregulation of KLF2 by AMPK plays an essential role in EPO-induced angiogenesis.

Different roles of ß-arrestin and the PKA pathway in mitochondrial ROS production induced by acute ß-adrenergic receptor stimulation in neonatal mouse cardiomyocytes.

Reactive oxygen species (ROS) play a crucial role in various physiological and pathological processes mediated by ß-adrenergic receptors (ß-ARs) in cardiomyocytes. However, the sources and signaling pathways involved in ROS production induced by acute ß-AR activation have not yet been fully defined. In primary neonatal mouse cardiomyocytes (NMCMs), the ß-AR agonist isoproterenol (ISO) induced a rapid increase in mitochondrial ROS and total ROS production. Both the expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2/4 (NOX 2/4) remained unchanged after 2 h of ISO treatment, suggesting that acute ISO stimulation mainly induces mitochondrial ROS production in NMCMs. Knockdown of ß-arrestin1, but not ß-arrestin2, inhibited ISO-induced mitochondrial ROS production within 1-2 h after ISO treatment. Moreover, forskolin, an adenylyl cyclase (AC) activator, rapidly increased mitochondrial ROS as early as 15 min after ISO treatment. Inhibition of the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway abolished the mitochondrial ROS production within 15-60 min after ISO treatment. In conclusion, mitochondria are the major source of ROS production upon acute ISO stimulation. ß-arrestin1, but not ß-arrestin2, is involved in ISO-induced mitochondrial ROS production. Upon acute ß-AR stimulation in NMCMs, the classical cAMP/PKA pathway is responsible for faster mitochondrial ROS production, whereas ß-arrestin1 signaling is responsible for slower mitochondrial ROS production.

Quantitative proteomics reveals key proteins regulated by eicosapentaenoic acid in endothelial activation.

Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid (PUFA), has been shown to decrease the risk of atherosclerosis by attenuating endothelial activation. In this study, we used mass spectrometry-based label-free quantitative proteomics to study the protective mechanisms of EPA and to identify key proteins that regulated by EPA in endothelial activation. Arachidonic acid (AA) was used as a control. HUVECs were pretreated with each of the two PUFAs, and then stimulated with TNFα as a model of endothelial activation. A total of 3391 proteins were identified, and 1958 proteins were quantified. Pearson's correlation coefficients revealed the excellent biological reproducibility of the proteomic results. Gene Ontology and KEGG enrichment analysis of differentially expressed proteins was performed, thus leading to the identification of the glutathione metabolism, oxidation reduction, and DNA replication as the most significantly enriched pathways. Seven key proteins were identified: elongation factor Tu (mitochondrial, TUFM), integrin alpha 6 (ITGA6), catalase (CAT), annexin A6 (ANXA6), heat shock 70 kDa protein 1A (HSPA1A), glutamate-cysteine ligase regulatory subunit (GCLM), and heme oxygenase 1 (HMOX1). Further connections among these proteins were also revealed by protein-protein interaction analysis. The mRNA levels of CAT, GCLM, and HMOX1 were verified with real-time PCR. The protein level of CAT was verified using Western blotting. This study is an in-depth proteomics analysis of EPA-treated cells and may provide possible insights into the molecular mechanisms of EPA's cytoprotective and atheroprotective effects.

Exacerbated cardiac fibrosis induced by ß-adrenergic activation in old mice due to decreased AMPK activity.

Senescent hearts exhibit defective responses to ß-adrenergic receptor (ß-AR) over-activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in protecting against ageing-associated cardiac remodelling in mice upon ß-AR over-activation. 10-week-old (young) and 18-month-old (old) mice were subcutaneously injected with the ß-AR agonist isoproterenol (ISO; 5 mg/kg). More extensive cardiac fibrosis was found in old mice upon ISO exposure than in young mice. Meanwhile, ISO treatment decreased AMPK activity and increased ß-arrestin 1, but not ß-arrestin 2, expression, and the effects of ISO on AMPK and ß-arrestin 1 were greater in old mice than in young mice. Similarly, young AMPKα2-knockout (KO) mice showed more extensive cardiac fibrosis upon ISO exposure than that was observed in age-matched wild-type (WT) littermates. The extent of cardiac fibrosis in WT old mice was similar to that in young KO mice. Additionally, AMPK activities were decreased and ß-arrestin 1 expression increased in KO mice. In contrast, the AMPK activator metformin decreased ß-arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure. In conclusion, more severe cardiac fibrosis is induced by ISO in old mice than in young mice. A decrease in AMPK activity, which further increases ß-arrestin 1 expression, is the central mechanism underlying the ageing-related cardiac fibrosis induced by ISO. The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon ß-AR over-activation.

Metformin is a novel suppressor for transforming growth factor (TGF)-ß1.

Metformin is a widely used first-line antidiabetic drug that has been shown to protect against a variety of specific diseases in addition to diabetes, including cardiovascular disorders, polycystic ovary syndrome, and cancer. However, the precise mechanisms underlying the diverse therapeutic effects of metformin remain elusive. Here, we report that transforming growth factor-ß1 (TGF-ß1), which is involved in the pathogenesis of numerous diseases, is a novel target of metformin. Using a surface plasmon resonance-based assay, we identified the direct binding of metformin to TGF-ß1 and found that metformin inhibits [(125)I]-TGF-ß1 binding to its receptor. Furthermore, based on molecular docking and molecular dynamics simulations, metformin was predicted to interact with TGF-ß1 at its receptor-binding domain. Single-molecule force spectroscopy revealed that metformin reduces the binding probability but not the binding force of TGF-ß1 to its type II receptor. Consequently, metformin suppresses type II TGF-ß1 receptor dimerization upon exposure to TGF-ß1, which is essential for downstream signal transduction. Thus, our results indicate that metformin is a novel TGF-ß suppressor with therapeutic potential for numerous diseases in which TGF-ß1 hyperfunction is indicated.