Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

Measurement of enzyme activity of insoluble substrates based on ordered porous layer interferometry and the application in evaluation of thrombolytic drugs.

The development of innovative methods for real-time surveillance of enzymatic activity determination processes is essential, particularly for insoluble substrate enzymatic assessments. In this work, a novel method for enzymatic activity determination was devised by assembling a 190 nm silica colloidal crystal (SCC) film onto a glass slide, coupled with Ordered Porous Layer Interferometry (OPLI) technology. By fixing the substrate of the enzyme on the surface of the silica sphere, a solid-liquid interface can be formed for monitoring enzymatic activity. The enzymatic activity is gauged by the change in the SCC film's thickness caused by the digestion of the loaded substrate. The procedure of chymotrypsin-mediated casein digestion was documented in real time, facilitating the examination of chymotrypsin's activity and kinetics. The newly-developed enzymatic activity determination method demonstrated exceptional sensitivity towards chymotrypsin activity, with a linear range spanning 0.0505-2.02 units per mg. Additionally, the method was extended to the assessment of fibrinolysis enzyme activity and kinetic analysis, yielding promising results. Therefore, this technique can serve as a real-time, user-friendly, cost-effective novel approach for enzymatic activity determination, providing fresh perspectives for enzymatic activity determination studies.

Risk factors and clinical prediction models for prolonged mechanical ventilation after heart valve surgery.

OBJECTIVES: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. METHODS: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. RESULTS: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042-1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007-3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002-1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275-0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005-1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. CONCLUSION: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.

Impact of nonalcoholic fatty liver disease status change on antiviral efficacy of nucleos(t)ide analogues in HBeAg-positive chronic hepatitis B.

Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.

CBL aggravates Ang II-induced cardiac hypertrophy via the VHL/HIF-1α pathway.

CBL (Casitas B cell lymphoma), an important ubiquitin protein ligase, is involved in protein folding, protein maturation, and proteasome-dependent protein catabolism in different cells. However, its role in cardiac hypertrophy is still unclear. In this study, we found that expression of CBL is increased in an Ang II-induced mouse cardiac hypertrophy animal model and in Ang II-treated H9C2 cells. Interference with CBL expression attenuates the degree of myocardial hypertrophy as well as the expression of hypertrophy-related genes in H9C2 cells. Further research found that CBL aggravates myocardial hypertrophy by activating HIF-1α, which is an aggravating factor for hypertrophy. The effect of CBL on promoting myocardial hypertrophy was reversed by interference with HIF-1α. Mechanistically, we found that CBL directly interacted with and degraded VHL by increasing its ubiquitination level, which is a widely accepted regulatory factor of HIF-1α. Finally, our results showed that CBL was partially dependent on degradation of VHL and that activation of HIF-1α promoted myocardial hypertrophy. Collectively, these findings suggest that strategies based on activation of the CBL/HIF-1α axis might be promising for the treatment of hypertrophic cardiomyopathy.

Blockage of PD-L1 by FERMT3-mediated Wnt/ß-catenin signalling regulates chemoresistance and immune evasion of colorectal cancer cells.

Colorectal cancer (CRC) constitutes a major public health problem because of the high rate of morbidity and mortality. Chemotherapy and immunotherapy are the major and promising strategies for cancer patients including CRC; nevertheless, chemoresistance and immune escape limit the final efficacy of the above approaches. FERMT3 has proven to exert a critical role in the immune system and has contradictive effects on cancer progression. In this study, bioinformatics database analysis and clinical specimen detection both corroborated the downregulation of FERMT3 in CRC tissues and cells. Of interest, overexpression of FERMT3 suppressed CRC cell invasion and sensitized cells to 5-fluorouracil (5-FU) by reducing cell viability and increasing cell apoptosis and caspase 3 activity. Noticeably, FERMT3 upregulation enhanced natural killer (NK) cells activation by increasing secretions of interferon γ (IFN-γ) and tumour necrosis factor α (TNF-α) when NK cells were co-cultured with CRC cells. Importantly, upregulation of FERMT3 promoted NK cell-mediated killing of CRC cells. Mechanically, FERMT3 inhibited the aberrant activation of Wnt/ß-catenin signalling and the subsequent programmed death-ligand 1 (PD-L1) expression in CRC cells. Moreover, knockdown of PD-L1 suppressed CRC cell invasion, 5-FU resistance and NK cells-mediated tumour killing. Additionally, reactivating the Wnt/ß-catenin signalling with a specific WNT agonist CAS 853220-52-7 overturned the efficacy of FERMT3 overexpression against CRC cell invasion, 5-FU chemoresistance and cell susceptibility to NK cell-mediated cytotoxicity. Therefore, the current findings substantiate that FERMT3 elevation may attenuate CRC cell chemoresistance and NK cell-mediated immune response to tumour cells by inhibiting Wnt/ß-catenin-PD-L1 signalling. Therefore, FERMT3 elevation may be a promising therapeutic approach to overcome chemoresistance and immune evasion in CRC.

Risk factors for illness severity in patients with COVID-19 pneumonia: a prospective cohort study.

Background: Although COVID-19 pneumonia is spreading internationally, knowledge regarding the factors associated with the illness severity of patients remains limited. We aimed to identify the factors associated with the disease severity of patients with COVID-19 pneumonia induced by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We prospectively enrolled a single-center case series of adult patients with COVID-19 admitted to the Infectious Disease Hospital of Jining, Jining City, Shandong Province, China, from January 24 to March 1, 2020. Demographics, clinical characteristics, and laboratory findings were compared to investigate the risk factors related with the disease severity of COVID-19 pneumonia patients. Results: We included a total of 78 patients with COVID-19 pneumonia, of whom 6 had the severe type. As compared to a moderately ill cohort, our analysis showed that shortness of breath, fatigue, longer days from illness onset to diagnosis confirmed, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, lymphocyte counts < 1.0 × 109/L, platelet < 100 × 109/L, C-reactive protein (CRP) > 10 mg/L, neutrophil to platelet ratio (NPR) > 2.3, neutrophil to lymphocyte ratio (NLR) > 3.9, aspartate aminotransferase (AST) > 40 U/L, albumin < 40 g/L, lactate dehydrogenase (LDH) > 245 U/L, and glucose > 6.1 mmol/L were predictors of disease severity in COVID-19 pneumonia. In the sex-, age-, and comorbid illness-matched case-control study, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L remained associated with the early detection and identification of severe patients. Conclusion: We demonstrated that neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L might predict the severity of illness in patients with COVID-19 pneumonia.

Protective mechanism of SIRT1 on Hcy-induced atrial fibrosis mediated by TRPC3.

High plasma levels of homocysteine (Hcy) are regarded as a risk factor for atrial fibrillation (AF), which is closely associated with the pathological consequence of atrial fibrosis and can lead to heart failure with a high mortality rate; here, we show that atrial fibrosis is mediated by the relationship between canonical transient receptor potential 3 (TRPC3) channels and sirtuin type 1 (SIRT1) under the stimulation of Hcy. The left atrial appendage was obtained from patients with either sinus rhythm (SR) or AF and used to evaluate the relationship between the concentration of Hcy and a potential mechanism of cardiac fibrosis mediated by TRPC3 and SIRT1. We next performed transverse aortic constriction (TAC) in mouse to investigate the relationship. The mechanisms underlying atrial fibrosis involving TRPC3 and SIRT1 proteins were explored by co-IP, BLI and lentivirus transfection experiments. qPCR and WB were performed to analyse gene and protein expression, respectively. The higher level of atrial fibrosis was observed in the HH mouse group with a high Hcy diet. Such results suggest that AF patients may be more susceptible to atrial fibrosis and possess a high probability of progressing to hyperhomocysteinemia. Moreover, our findings are consistent with the hypothesis that TRPC3 channel up-regulation leads to abnormal accumulation of collagen, with the down-regulation of SIRT1 as an aetiological factor of high Hcy, which in turn predisposes to atrial fibrosis and strongly enhances the possibility of AF.

Citrate pretreatment attenuates hypoxia/reoxygenation-induced cardiomyocyte injury via regulating microRNA-142-3p/Rac1 aix.

Purpose: Citrate has a positive effect on improving the pathophysiological changes of cardiomyocytes such as cardiac failure and auricular fibrillation. However, the underlying mechanism remains still unclear.Methods: Rat cardiomyocytes were used to establish hypoxia/reoxygenation (H/R) cell model. Citrate was conduct to pretreat with cardiomyocytes, and microRNA-142-3p (miR-142-3p) knockdown and overexpression were used to determine the underlying mechanism of their functions in cardiomyocytes. Cell viability and apoptosis were respectively detected by CCK-8 and flow cytometry. Protein and mRNA levels were determined by Western blot and qRT-PCR. Luciferase reporter assay and Targetscan were performed to study the regulation of miR-142-3p and Rac1.Results: The level of miR-142-3p was down-regulated in H/R model, but up-regulated in cardiomyocytes following citrate treatment. Citrates attenuated H/R injury induced miR-142-3p level and cell viability, and also inhibited H/R injury induced apoptosis, LDH, MDA and autophagy. Cell viability was improved, and autophagy was suppressed by miR-142-3p mimic, while inhibitor had opposite results. Compared with H/R + miR-142-3p inhibitor group, cell viability was higher, and apoptosis and autophagy were lower in Cit + H/R + miR-142-3p inhibitor group. Furthermore, Rac1 was target gene of miR-142-3p, and decreased by citrate, in comparison with H/R + miR-142-3p inhibitor group.Conclusion: Taken together, our findings indicated that citrate ameliorates H/R injury-induced cardiomyocytes autophagy by regulating miR-142-3p/Rac1 aix.

A Hybrid Procedure Combining Mini-Thoracotomy with Interventional Endocardial Lead Implantation for Cardiac Resynchronization Therapy in Patients with Chronic Congestive Heart Failure: A Report of Four Cases.

BACKGROUND: We describe the application and effectiveness of transthoracic electrode implantation for epicardial left ventricular pacing in cardiac resynchronization therapy (CRT) for patients with chronic congestive heart failure. METHODS: We assessed four patients with chronic congestive heart failure for whom implantation of endocardial electrodes was contraindicated. The epicardial electrodes were implanted via a mini-thoracotomy in the fourth or fifth left intercostal space. We analyzed the surgical implantation technique and the short-term effectiveness of the procedure. RESULTS: The epicardial electrodes successfully were implanted in all four patients. The patients' hemodynamic status, cardiac function, and symptoms significantly improved. Patients I, II, III, and IV were discharged from the hospital on the 8, 11, 4, and 7 days, respectively, after the operation. Follow up lasted for 12 months. None of the patients presented with electrode fractures or surgical wound infections, and the pacing threshold and electrode impedance were normal. In one case, phrenic nerve stimulation occurred due to the low placement position of the electrode. When the electrode was moved slightly inward and upward, the sacral nerve stimulation sign disappeared, and no other complications were noted. One patient developed capsule infection, and the presence of an ectopic pacemaker was noted; therefore, a pacemaker replacement procedure was required. CONCLUSION: In CRT, the implantation of a left ventricular epicardial electrode through a left-sided small incision is safe, feasible, and effective. This hybrid surgery combining interventional and cardiac techniques can maximize the curative effect of CRT.

Surgical Treatment of Coronary Pseudoaneurysm: A Case Report and Literature Review.

A coronary pseudoaneurysm is a rare complication of chest trauma. In this report, we describe the case of a 65-year-old man with a mediastinal lesion. On admission, he complained of chest tightness and dry cough, and a pseudoaneurysm was confirmed in the left anterior descending branch of the coronary artery on chest computerized tomography, angiography, and coronary angiography. The patient had experienced chest trauma 5 years previously. With the help of extracorporeal bypass surgery, the pseudoaneurysm was resected under direct observation. The patient recovered well after surgery. Traumatic coronary artery pseudoaneurysms usually are asymptomatic and often misdiagnosed. Preoperative coronary angiography is a crucial diagnostic used for deciding appropriate surgical management.

[Pirfenidone Inhibits Cytokines/chemokines Release from Alveolar Macrophages].

Objective To investigate the effect of pirfenidone on cytokine/chemokine production by alveolar macrophages(AMs)in patients with idiopathic nonspecific interstitial pneumonia(iNSIP)or idiopathic pulmonary fibrosis(IPF).Methods We prospectively enrolled 10 iNSIP patients,11 IPF patients,and 8 non-interstitial lung disease(non-ILD)patients(control group)from our center from January 2015 to December 2018.AMs from bronchoalveolar lavage fluid(BALF)were cultured with or without lipopolysaccharide(LPS)stimulation.The production of Th1 cytokines [soluble tumor necrosis factor receptor(sTNFR)-1,sTNFR-2,and interleukin(IL)-1ß],Th2 cytokines [IL-10 and granulocyte-macrophage colony-stimulating factor(GM-CSF)],angiogenic chemokines [IL-18 and macrophage inflammatory protein(MIP)-1ß],and angiostatic chemokines [interferon-gama inducible monokines(MIG)and interferon-gama inducible protein(IP-10)] in the culture supernatants were measured by a bead-based assay,Luminex.The effect of pirfenidone on the cytokine/chemokine production was tested at various concentrations(0,0.03,0.10,0.30 mg/ml).Results The spontaneous and LPS-stimulated release of TNF-α,sTNFR-1,sTNFR-2,IL-1ß,IL-10,MIP-1ß,MIG,and IP-10 by AMs were significantly increased in iNSIP and IPF groups compared with control group(all P<0.05),but no difference in IL-18 was seen among three groups(all P>0.05).MIG and IP-10 were significantly higher in iNSIP group than in IPF group(both P<0.05).Pirfenidone suppressed the spontaneous and LPS-stimulated AMs release of all studied cytokine/chemokine in iNSIP and IPF in a dose-dependent manner at concentrations of 0.10 and 0.30 mg/ml,and no difference was observed between iNSIP and IPF groups(both P>0.05).Conclusion Pirfenidone can markedly suppress cytokine/chemokine expression in iNSIP and IPF patients,but the difference is not significant between these two groups of patients.

FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways.

High fibroblast growth factor 23 (FGF23) concentrations are a strong predictor of atrial fibrillation (AF), but researchers have not clearly determined the mechanism by which FGF23 causes atrial fibrosis in patients with AF. This study aims to elucidate the mechanism by which FGF23 induces atrial fibrosis in patients with AF. Immunohistochemistry was used to study the expression of FGF23, FGFR4, and fibrotic factors in patients with a normal sinus rhythm (SR) and patients with AF. Cardiac fibroblasts (CFs) were cocultured with different concentrations of the recombinant FGF23 protein. Compared with the SR group, the levels of FGF23, FGFR4, α-smooth muscle actin (α-SMA), and collagen-1 were significantly increased in the AF group. Exposure to high concentrations of the recombinant FGF23 protein increased the accumulation of reactive oxygen species (ROS) and activated α-SMA, collagen-1, signal transducer and activator of transcription 3 (STAT3) and SMAD3 signaling in cultured CFs. The levels of fibrotic proteins in CFs stimulated with high concentrations of the recombinant FGF23 protein were reversed by N-acetylcysteine (NAC, a ROS inhibitor), ship information system 3 (a SMAD3 inhibitor), and Stattic (a STAT3 inhibitor). Furthermore, compared to untreated CFs, CFs treated with the recombinant FGF23 protein were characterized by an increased interaction between STAT3 and SMAD3. Based on these results, FGF23 induces atrial fibrosis in patients with AF by increasing ROS production and subsequently activating STAT3 and SMAD3 signaling.

Ferrocenyl-Triphenyltin Complexes as Lysosome-Targeted Imaging and Anticancer Agents.

In this paper, two ferrocenyl-triphenyltin complexes were synthesized and characterized. Complex 2 is constructed as new multifunctional therapeutic platform for lysosome-targeted imaging and displayed much higher cytotoxicity than its analogue 1 by the introduction of a methyl group instead of a hydrogen atom in acylhydrazone. The cyclic voltammograms and reaction with GSH (glutathione) further confirmed that complex 1 has a reversible redox peak and can react with GSH, which indicate that complex 1 might lose its anticancer effect by undergoing reaction with GSH once it enters the cancer cell. Complex 2 could effectively catalyze the oxidation of NADH (the reduced form of nicotinamide adenine dinucleotide) to NAD+ and induce the production of reactive oxygen species (ROS), lead to caspase-dependent apoptosis through damaged mitochondria, simultaneously, accounting for the mitochondrial vacuolization and karyorrhexis. The caspase-3 activation and cytoplasmic vacuolation karyorrhexis induced by complex 2 revealed that the A549 cell lines might undergo cell death primarily mediated by apoptosis and oncosis; however, 1 cannot reproduce this effect. Taken together, these results indicated that complex 2 has more potential for evolution as a new bioimaging and anticancer agent.

MicroRNA-591 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Lowering Drug Resistance through Inhibition of Far-Upstream Element-Binding Protein 2-Mediated Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Axis.

MicroRNAs, a group of noncoding regulatory RNAs, are involved in oncogenesis, cell survival, and chemosensitivity. First, microarray-based analysis predicted that far-upstream element-binding protein 2 (FBP2) was upregulated in hepatocellular carcinoma (HCC), which may be regulated by miR-591. In this study, we hypothesize an inhibitory role of miR-591 in HCC via regulating FBP2. Next, reverse transcription quantitative polymerase chain reaction found that FBP2 expressed highly and miR-591 expresses poorly in HCC tissues. Then, the negative correlation between miR-591 and mRNA expression of FBP2 was identified by Pearson's correlation coefficient, and putative miR-591-binding sites on the 3'-untranslated region of FBP2 was validated using a dual-luciferase reporter gene assay. After the expression of miR-591 and FBP2 was altered in the drug-resistant CD133+/CD44+ cells, a series of in vitro and in vivo experiments demonstrated that either miR-591 overexpression or FBP2 silencing inhibited the abilities of sphere formation and colony formation, drug resistance, as well as tumorigenicity. It was further observed that miR-591 could suppress FBP2 expression by blocking the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin axis. Above results highlighted an inhibitory effect of miR-591 on the development of HCC by reducing the drug resistance of HCC stem cells. It revealed miR-591 as a new target in the treatment of HCC.

Serine Protease from Nereis virens Inhibits H1299 Lung Cancer Cell Proliferation via the PI3K/AKT/mTOR Pathway.

This study explores the in vitro anti-proliferative mechanism between Nereis Active Protease (NAP) and human lung cancer H1299 cells. Colony formation and migration of cells were significantly lowered, following NAP treatment. Flow cytometry results suggested that NAP-induced growth inhibition of H1299 cells is linked to apoptosis, and that NAP can arrest the cells at the G0/G1 phase. The ERK/MAPK and PI3K/AKT/mTOR pathways were selected for their RNA transcripts, and their roles in the anti-proliferative mechanism of NAP were studied using Western blots. Our results suggested that NAP led to the downregulation of p-ERK (Thr 202/Tyr 204), p-AKT (Ser 473), p-PI3K (p85), and p-mTOR (Ser 2448), suggesting that NAP-induced H1299 cell apoptosis occurs via the PI3K/AKT/mTOR pathway. Furthermore, specific inhibitors LY294002 and PD98059 were used to inhibit these two pathways. The effect of NAP on the downregulation of p-ERK and p-AKT was enhanced by the LY294002 (a PI3K inhibitor), while the inhibitor PD98059 had no obvious effect. Overall, the results suggested that NAP exhibits antiproliferative activity by inducing apoptosis, through the inhibition of the PI3K/AKT/mTOR pathway.

Pacemaker Dysfunction due to a Large Thrombus on Ventricular Lead.

BACKGROUND: Pacemaker lead-related thrombosis is a rare but severe complication in patients with pacing lead implantation in the right ventricle. We present a case with recurrent syncope after single-chamber implantable cardioverter defibrillator (ICD) implantation. Pacing lead-related thrombosis was observed during open-heart surgery. This induced intermittent pacemaker dysfunction and recurrent syncope. CASE PRESENTATION: A 67-year-old male patient presented with frequent episodes of syncope and a history of dilated cardiomyopathy and paroxysmal ventricular tachycardia. Normal coronary angiography was found, and therefore a single-chamber ICD was implanted into the right ventricle to prevent cardiac events in 2013. However, he was referred to our hospital because of recurrent syncope 3 to 4 years after ICD implantation. A comprehensive investigation was performed to find out the etiology for the recurrent syncope. Pacing lead thrombosis was finally observed during open-heart surgery, which can introduce intermittent pacemaker dysfunction. After the thrombus was removed and the lead was separated from the posterior leaflet of the tricuspid valve, the ICD functioned normally after reprogramming. Oral anticoagulant was prescribed after discharging. During the 1-year follow-up period, this patient was free of syncope. CONCLUSIONS: This case illustrated that pacemaker lead-associated thrombosis should be considered when the cardiac implantable electronic device fails to prevent patients from having cardiac events. Oral anticoagulant might be important for preventing thrombosis among patients with ICD implantation into the right ventricle.

Associations of candidate gene polymorphisms with poor responsiveness to aspirin: a meta-analysis.

Recently, the roles of gene polymorphisms in poor responsiveness to aspirin were extensively investigated, with conflicting results. Therefore, we performed this meta-analysis to better assess the relationship between candidate genetic variants and poor responsiveness to aspirin. Eligible articles were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to detect possible associations of gene polymorphisms with poor responsiveness to aspirin. Among 53 eligible articles, a total of 22 candidate gene polymorphisms were analyzed. A significant association with poor responsiveness to aspirin was observed for GP1BA rs2243093, PTGS1 rs1330344, PTGS2 rs689466 and TBXA2R rs1131882 polymorphisms in overall analyses. Further subgroup analyses demonstrated that ITGA2 rs1126643, PTGS1 rs1330344, PTGS2 rs20417, PTGS2 rs689466 and TBXA2R rs1131882 polymorphisms were significantly associated with poor responsiveness to aspirin in Asians, whereas only GP1BA rs2243093 polymorphism was significantly correlated with this phenomenon in Caucasians. In conclusion, our findings indicate that GP1BA rs2243093, ITGA2 rs1126643, PTGS1 rs1330344, PTGS2 rs20417, PTGS2 rs689466 and TBXA2R rs1131882 polymorphisms may serve as genetic biomarkers of poor responsiveness to aspirin in certain ethnic groups. This article is protected by copyright. All rights reserved.

Impact of Genetic Variation in Aldehyde Dehydrogenase 2 and Alcohol Consumption on Coronary Artery Lesions in Chinese Patients with Stable Coronary Artery Disease.

The aim of this study is to investigate the impact of aldehyde dehydrogenase 2 (ALDH2) genotype and alcohol consumption on coronary artery lesions in Chinese patients with stable coronary artery disease (CAD). A total of 753 Chinese patients (73.6% male) diagnosed with stable CAD by coronary angiography were included in the sample. The frequency of the mutated type ALDH2*2 (including ALDH2*1/*2 and ALDH2*2/*2) was 44.1% in CAD patients. The mutated ALDH2 carriers were more susceptible to multivessel lesions. Low to moderate alcohol consumption is related to higher plasma HDL-C level and fewer coronary artery lesions in CAD patients with ALDH2 wild genotype, while these effects were not observed in CAD patients with ALDH2 mutated genotype. Furthermore, we divided the mutated group into heterozygous and homozygous subgroups, and no obvious relationships were observed among drinking and HDL-C and coronary lesions. To explore the metabolic effects of ALDH2 modified by alcohol, we examined the impact of ALDH2 genotype and alcohol intake on HDL-C levels in ALDH2 wild type and knockout mice. The results showed HDL-C levels were significantly higher post low to moderate alcohol consumption in wild type rather than in knockout mice. CAD patients with mutated ALDH2 genotype are inclined to suffer with coronary artery lesions than wild type subjects. Low to moderate ethanol intake contributes to fewer multivessel lesions in CAD patients with ALDH2 wild type, which might be related to higher HDL-C level.

Quantitative comparison of MR diffusion-weighted imaging for liver focal lesions between 3.0T and 1.5T: Regions of interest of the minimum-spot ADC, the largest possible solid part, and the maximum diameter in lesions.

PURPOSE: To quantitatively compare the apparent diffusion coefficient (ADC) values of 3.0T and 1.5T magnetic resonance (MR) diffusion-weighted imaging (DWI) protocols using regions of interest (ROIs) for the minimum ADC, largest solid part, and maximum diameter of lesions, for the detection of liver focal lesions. MATERIALS AND METHODS: In total, 26 patients with 28 liver focal lesions prospectively underwent both 1.5T and 3.0T DWI of the liver. The protocols included respiratory-triggered (RT), breath-holding (BH), and free-breathing (FB) acquisitions. The ADC values were measured at both field strengths using three methods: ROIs with the minimum ADC, the largest solid part, and the maximum diameter of lesions. Bland-Altman tests and paired t-tests were used to compare ADC values in the liver focal lesions obtained at 1.5T and 3.0T. RESULTS: The 3.0T and 1.5T protocols differed significantly with regard to the ADC values of the RT, BH, and FB acquisitions, for ROIs of both the largest solid part (P = 0.005, P = 0.014, and P = 0.022, respectively) and maximum diameter of lesions (P < 0.001, P = 0.001, and P = 0.001, respectively). CONCLUSION: When using DWI for quantitative analysis of liver focal lesions, field strength could exert a negative effect depending on the ROI. The ADC values from ROIs of both the largest solid part and maximum diameter of lesions may differ between 1.5T and 3.0T protocols.J. Magn. Reson. Imaging 2016;44:1320-1329.