Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy:A case report

BACKGROUND Bradycardia-induced cardiomyopathy(BIC),which is a disease resulting from bradycardia,is characterized by cardiac chamber enlargement and diminished cardiac function.The correction of bradycardia can allow for significant improvements in both cardiac function and structure;however,this disease has been infrequently documented.In this case,we conducted a longitudinal followup of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.CASE SUMMARY A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7.Since she had no obvious symptoms,she did not receive any treatment to improve her bradycardia during the 42-year follow-up,except for the implantation of a temporary pacemaker during labor induction surgery.As time progressed,the patient's heart gradually expanded due to her low ventricular rate,and she was diagnosed with BIC.In 2014,the patient developed atrial fibrillation,her ventricular rate gradually increased,and her heart shape gradually returned to normal.This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years,introduces another possible outcome of BIC,and emphasizes the importance of early intervention in treating BIC.CONCLUSION BIC can induce atrial fibrillation,causing an increased ventricular rate and leading to positive cardiac remodeling.

Feasibility and efficacy of endoscopic purse-string suture-assisted closure for mucosal defects induced by endoscopic manipulations

BACKGROUND Large or transmural defects induced by gastrointestinal endoscopic manipulations are difficult to close,although complete closure is recommended for better recovery.Endoscopic purse-string assisted suturing(EPSS)has been used in clinical practice and has proven to be an effective and safe technique for the closure of large mucosal defects.However,details regarding the efficacy of endoscopic pre-purse-string suture(P-EPSS)are unknown,especially that it offers several advantages over conventional EPSS(C-EPSS).AIM To elucidate the outcomes of EPSS-assisted closure in different clinical situations,and evaluate the efficacy of P-EPSS.METHODS This retrospective observational study included a total of 180 patients who underwent closure assisted by P-EPSS(n=63)or C-EPSS(n=117)between July 2014 and June 2020.The P-EPSS and C-EPSS groups were compared and the intergroup differences in aspects such as the lesion size,location,and morphology,incidence of complete closure,intraoperative perforation,and delayed adverse events were evaluated.Data on the features and clinical course of cases with adverse events were collected for further analysis.RESULTS Patients with lesion size larger than 3 cm,lesions located at the fundus of stomach,or submucosal tumors originating from the deep mucosa were more likely to undergo P-EPSS-assisted closure.The P-EPSS group showed a significantly higher proportion of intraoperative perforation(56%vs 17%)and a much shorter procedure time(9.06±6.14 min vs 14.84±7.25 min).Among adverse events,the incidence of delayed perforation(5%vs 4%;P=0.82)and delayed bleeding(3%vs 4%;P=0.96)did not differ significantly between the groups.Multivariate analysis revealed that lesions with incomplete closure[odds ratio(OR)=21.33;95%confidence interval(CI):5.45-83.45;P<0.01]or size greater than 3 cm(OR=3.14;95%CI:1.08-9.18;P=0.039)showed a statistical tendency to result in an increase in delayed adverse events.CONCLUSION The present study revealed that EPSS could achieve secure complete closure of mucosal defect.PEPSS could shorten the procedure and yield complete closure of mucosal defects.Rather than closure-type selection,incomplete closure or lesion size larger than 3 cm were associated with worse outcomes.

Zinc-α2-glycoprotein 1 attenuates non-alcoholic fatty liver disease by negatively regulating tumour necrosis factor-α

BACKGROUND Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation;enhance steatogenesis, including promoting lipogenesis [sterol regulatory elementbinding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α];accelerate proliferation;and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.

Efficacy and safety of gemcitabine-based chemotherapies in biliary tract cancer:A meta-analysis

AIM:To investigate the efficacy and safety of gemcitabine(Gem)-based combination chemotherapies for the treatment of advanced biliary tract cancer.METHODS:Clinical trials were identified by searching scientific literature databases(Pub Med,EMBASE and the Cochrane Library)for studies published between1975 and 2013.Two reviewers independently evaluated the relevant studies and manually searched references from these reports to locate additional eligible studies.The disease response and control rates,progressionfree and overall survivals,and the grade 3-4 toxicities were evaluated by a meta-analysis.Odds-ratios(ORs)of the disease response and control rates and grade3-4 toxicities,and the mean difference(MD)of both progression-free and overall survivals were calculated and used for statistical analysis.RESULTS:Seven randomized trials with a total of 858patients were selected and included in the final analysis.The studies were divided into subgroups based on the chemotherapy regimens,including Gem-based and non-Gem-based chemotherapies.The overall analyses revealed that the patients treated with Gem-based combination chemotherapy had significantly higher disease response rates[OR=1.69,95%confidence interval(CI):1.17-2.43;P=0.01],a longer progressionfree survival(MD=1.95,95%CI:0.90-3.00;P=0.00)and a longer overall survival(MD=1.85,95%CI:0.26-3.44;P=0.02).A higher incidence of grade 3-4hematological toxicities,including leukopenia(OR=2.98,95%CI:1.44-6.20;P=0.00),anemia(OR=2.96,95%CI:1.79-4.92;P=0.00)and neutropenia(OR=2.80,95%CI:1.39-5.64;P=0.00)was found in the Gem-based combination chemotherapy group compared with the Gem monotherapy and non-Gem-based chemotherapy groups.CONCLUSION:Gem-based combination chemotherapy is a potential first-line treatment for advanced biliary tract cancer as a result of improved survival,though with additional toxicity.

MicroRNA-194 inactivates hepatic stellate cells and alleviates liver fibrosis by inhibiting AKT2

BACKGROUND Activation of hepatic stellate cells(HSCs)is a pivotal event in the onset and progression of liver fibrosis.Loss of microRNA-194(miR-194)has been reported in activated HSCs,but the actual role of miR-194 in liver fibrosis remains uncertain.AIM To explore the role and potential mechanism of miR-194-mediated regulation of liver fibrosis in vitro and in vivo.METHODS The expression of miR-194 was examined in human fibrotic liver tissues,activated HSCs,and a carbon tetrachloride(CCl4)mouse model by qPCR.The effects of AKT2 regulation by miR-194 on the activation and proliferation of HSCs were assessed in vitro.For in vivo experiments,we reintroduced miR-194 in mice using a miR-194 agomir to investigate the functions of miR-194 in liver fibrosis.RESULTS MiR-194 expression was notably lacking in activated HSCs from both humans and mice.Overexpression of miR-194(OV-miR-194)inhibitedα-smooth muscle actin(α-SMA)and type I collagen(Col I)expression and suppressed cell proliferation in HSCs by causing cell cycle arrest in G0/G1 phase.AKT2 was predicted to be a target of miR-194.Notably,the effects of miR-194 knockdown in HSCs were almost blocked by AKT2 deletion,indicating that miR-194 plays a role in HSCs via regulation of AKT2.Finally,miR-194 agomir treatment dramatically ameliorated liver fibrosis in CCl4-treated mice.CONCLUSION We revealed that miR-194 plays a protective role by inhibiting the activation and proliferation of HSCs via AKT2 suppression.Our results further propose miR-194 as a potential therapeutic target for liver fibrosis.

Lipotoxic hepatocyte-derived exosomal miR-1297 promotes hepatic stellate cell activation through the PTEN signaling pathway in metabolic-associated fatty liver disease

BACKGROUND Exosomes play an important role in metabolic-associated fatty liver disease(MAFLD),but the mechanism by which exosomes participate in MAFLD still remain unclear.AIM To figure out the function of lipotoxic exosomal miR-1297 in MAFLD.METHODS MicroRNA sequencing was used to detect differentially expressed miRNAs(DEmiR)in lipotoxic exosomes derived from primary hepatocytes.Bioinformatic tools were applied to analyze the target genes and pathways regulated by the DE-miRs.Quantitative real-time PCR(qPCR)was conducted for the verification of DEmiRs.qPCR,western blot,immunofluorescence staining and ethynyl-20-deoxyuridine assay were used to evaluate the function of lipotoxic exosomal miR-1297 on hepatic stellate cells(LX2 cells).A luciferase reporter experiment was performed to confirm the relationship of miR-1297 and its target gene PTEN.RESULTS MicroRNA sequencing revealed that there were 61 exosomal DE-miRs(P<0.05)with a fold-change>2 from palmitic acid treated primary hepatocytes compared with the vehicle control group.miR-1297 was the most highly upregulated according to the microRNA sequencing.Bioinformatic tools showed a variety of target genes and pathways regulated by these DE-miRs were related to liver fibrosis.miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes by qPCR.Fibrosis promoting genes(α-SMA,PCNA)were altered in LX2 cells after miR-1297 overexpression or miR-1297-rich lipotoxic exosome incubation via qPCR and western blot analysis.Immunofluorescence staining and ethynyl-20-deoxyuridine staining demonstrated that the activation and proliferation of LX2 cells were also promoted after the above treatment.PTEN was found to be the target gene of miR-1297 and knocking down PTEN contributed to the activation and proliferation of LX2 cells via modulating the PI3K/AKT signaling pathway.CONCLUSION miR-1297 was overexpressed in exosomes derived from lipotoxic hepatocytes.The lipotoxic hepatocyte-derived exosomal miR-1297 could promote the activation and proliferation of hepatic stellate cells through the PTEN/PI3K/AKT signaling pathway,accelerating the progression of MAFLD.

An initial study on liner-like Z-pinch loads with a novel configuration on Qiangguang-I facility

A series of liner-like Z-pinch loads with a novel configuration have been investigated experimentally for the first time on Qiangguang-I facility in China.The metallic layer is sputtered on the inner surface of the cylindrical SiO 2 substrate tube.In the preliminary experiment,the electric current flowed through the metallic load during the prepulse.However,the currents also flowed through the outer surface of the SiO 2 substrate during the main pulse.After the dielectric length had been increased in the formal experiment,most of the current flowed through the metallic load until radial radiation peak was measured by radiation monitor.As the line mass of the metallic load increases,the peak time of radial radiation also increases.Axial ultravi-olet frames indicate that the radiations are nearly azi-muthally uniform at first,but the uniformity becomes worse after radial radiation peak.The clearly separated boundary between the metal plasmas and the substrate has not been observed in the experiment.Experimental results are discussed and compared with simulation using the one-dimension radiation hydrodynamics code MULTI-IFE.

临夏州多民族青少年近视患病率调查及相关因素分析

目的:研究临夏州青少年近视患病率情况及影响近视发生的因素。方法:采用整群抽样方法抽取6～18岁青少年8 683例作为研究对象,检测其视力、屈光度等,同时采用调查问卷收集其性别、年龄、民族、用眼习惯等资料。结果:本次调查研究纳入的研究对象近视患病率为42.80%,不同民族研究对象近视患病率分别为藏族(59.05%)、汉族(46.71%)、东乡族(46.36%)、土族(45.24%)、撒拉族(41.30%)、保安族(40.61%)、回族(31.97%),差异有统计学意义(χ~2=44.08,P=0.007)。多因素Logistic回归分析表明课间休息时在室外活动是近视的保护因素,而年龄、周末及节假日使用电子产品、在家学习使用房间同一照明是近视的危险因素。结论:临夏州青少年近视患病率随年龄增大而升高,不同民族青少年近视患病率存在差异。教育部门与家庭应共同努力,增加青少年户外活动时间,改善青少年用眼环境,减缓青少年近视的发生发展。

Genetic diversity and structure of Rhododendron meddianum,a plant species with extremely small populations

Rhododendron meddianum is a critically endangered species with important ornamental value and is also a plant species with extremely small populations.In this study,we used double digest restriction-siteassociated DNA sequencing(ddRAD)technology to assess the genetic diversity,genetic structure and demographic history of the three extant populations of R.meddianum.Analysis of SNPs indicated that R.meddianum populations have a high genetic diversity(p?0.0772±0.0024,HE?0.0742±0.002).Both FST values(0.1582e0.2388)and AMOVA showed a moderate genetic differentiation among the R.meddianum populations.Meanwhile,STRUCTURE,PCoA and NJ trees indicated that the R.meddianum samples were clustered into three distinct genetic groups.Using the stairway plot,we found that R.meddianum underwent a population bottleneck about 70,000 years ago.Furthermore,demographic models of R.meddianum and its relative,Rhododendron cyanocarpum,revealed that these species diverged about 3.05(2.21e5.03)million years ago.This divergence may have been caused by environmental changes that occurred after the late Pliocene,e.g.,the Asian winter monsoon intensified,leading to a drier climate.Based on these findings,we recommend that R.meddianum be conserved through in situ,ex situ approaches and that its seeds be collected for germplasm.

Analysis on the situation and countermeasures of water resources supply and demand in the cities of small and medium-sized river basins along southeast coast of China-taking Xiamen City as an example

The small and medium-sized river basins along southeast coast of China hold comparatively abundant water resources.However,the rapid resources urbanization in recent years has produced a series of water problems such as deterioration of river water quality,water shortage and exacerbated floods,which have constrained urban economic development.By applying the principle of triple supply-demand equilibrium,this paper focuses on the estimation of levels of water supply and demand in 2030 at different guarantee probabilities,with a case study of Xiamen city.The results show that water shortage and inefficient utilization are main problems in the city,as the future water supply looks daunting,and a water shortage may hit nearly 2×10^(8)m^(3)in an extraordinarily dry year.Based on current water supply-demand gap and its trend,this paper proposes countermeasures and suggestions for developing and utilizing groundwater resources and improving the utilization rate of water resources,which can supply as a reference for other southeast middle-to-small-sized basin cities in terms of sustainable water resources and water environment protection.