Effects of loneliness and isolation on cardiovascular diseases:a two sample Mendelian Randomization Study

BACKGROUND Loneliness and isolation are associated with multiple cardiovascular diseases(CVDs),but there is a lack of research on whether they were causally linked.We conducted a Mendelian Randomization(MR)study to explore causal relationships between loneliness and isolation and multiple CVDs.METHODS Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study(GWAS)of 455,364 individuals of European ancestry in the IEU GWAS database.Summary data for 15 CVDs were also obtained from the IEU GWAS database.We used three MR methods including inverse variance weighting,MR-Egger,and weighted median estimation to assess the causal effect of exposure on outcomes.Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy.RESULTS MR analysis showed that loneliness and isolation were significantly associated with essential hypertension(OR=1.07,95%CI:1.03-1.12),atherosclerotic heart disease(OR=1.04;95%CI:1.02-1.06),myocardial infarction(OR=1.02;95%CI:1-1.04)and angina(OR=1.04;95%CI=1.02-1.06).No heterogeneity and pleiotropy effects were found in this study.CONCLUSIONS Causal relationship of loneliness and isolation with CVDs were found in this study.

Status of cardiovascular disease in China

Cardiovascular disease(CVD)has become the leading cause of death and disability in the global population and imposes a significant economic burden on global health systems.Prevalent cases of total CVD nearly doubled from 271 million in 1990 to 523 million in 2019,and the number of CVD deaths steadily increased from 12.1 million in 1990,reaching 18.6 million in 2019.The global trends for disabilityadjusted life years and years of life lost also increased significantly,and years lived with disability doubled from 17.7 million to 34.4 million over that period.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Evolving of treatment options for cerebral infarction

In this editorial,we comment on a recent article which addressed the therapeutic effect of aspirin plus edaravone in patients with cerebral infarction(CI).Herein,we outline the progress in therapy of CI.Apart from thrombolysis,aspirin is the most effective treatment for CI.Edaravone,a free radical scavenger,reduces endothelial cell damage and delays neuronal cell death.Aspirin plus edaravone mitigates damage to brain tissue by different mechanisms,thereby expediting the reinstation of neurological function.However,the nephrotoxic effect of edaravone,along with gastrointestinal bleeding associated with aspirin,may restrict this combination therapy.Although clinical studies have demonstrated the efficacy of thrombolytic therapy and mechanical thrombectomy,patients receiving these treatments experience modest efficacy and many adverse events.Moreover,interest in exploring natural medicines for CI is increasing,and they appear to have a high potential to protect against CI.The evolution of therapeutic strategies is expected to improve clinical outcomes of patients with CI.

Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease

Xiaoyao San(XYS)is a classic Chinese medicine prescription.It is traditionally used to relieve syndrome of“liver stagnation and spleen deficiency”,a common syndrome type in traditional Chinese medicine,through soothing liver,tonifying spleen,and nourishing blood.Correspondingly,XYS has long application in the treatment of depression,dyspepsia and liver diseases.Given the rising of cutting-edge researches on XYS,there’s a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Evolution of treatment options for juvenile idiopathic arthritis

A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs(NSAIDs)for juvenile idiopathic arthritis(JIA).Herein,we outline the progress in drug therapy of JIA.NSAIDs have traditionally been the primary treatment for all forms of JIA.NSAIDs are symptom-relief medications,and well tolerated by patients.Additionally,the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional NSAIDs.Glucocorticoid is another kind of symptom-relief medications with potent anti-inflammatory effect.However,the frequent adverse events limit the clinical use.Both NSAIDs and glucocorticoid fail to ease or pre-vent joint damage,and the breakthrough comes along with the disease-mo-difying antirheumatic drugs(DMARDs).DMARDs can prevent disease pro-gression and reduce joint destruction.Particularly,the emergence of biologic DMARDs(bDMARDs)has truly revolutionized the therapeutics of JIA,compared with conventional synthetic DMARDs.As a newly developed class of drugs,the places of most bDMARDs in the management of JIA remain to be well estab-lished.Nevertheless,the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for JIA.

Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma

In this editorial,we comment on the article(World J Gastrointest Oncol 2024;16:1236-1247),which is a retrospective study of transarterial chemoembolization(TACE)combined with multi-targeted tyrosine kinase inhibitor(TKI)and programmed cell death protein-1(PD-1)inhibitor for the treatment of unresectable hepatocellular carcinoma(HCC).Herein,we focus specifically on the mechanisms of this triple therapy,administration sequence and selection of each medication,and implications for future clinical trials.Based on the interaction mechanisms between medications,the triple therapy of TACE+TKI+PD-1 is proposed to complement the deficiency of each monotherapy,and achieve synergistic antitumor effects.Although this triple therapy has been evaluated by several retrospective trials,it is still controversial whether the triple therapy achieves better clinical benefits,due to the flawed study design and heterogeneity in medications.In addition,the administration sequence,which may greatly affect the clinical benefit,needs to be fully considered at clinical decision-making for obtaining better prognosis.We hope that this editorial could contribute to the design and optimization of future trials.

Different clinical characteristics and outcomes of hypertrophic cardiomyopathy with and without hypertension:seeking the truth

OBJECTIVE To determine the different clinical characteristics and outcomes of hypertrophic cardiomyopathy(HCM)patients with and without hypertension(HT).METHODS A total of 696 HCM patients were included in this study and all HCM diagnoses were confirmed by the genetic test.Patients were analyzed separately in the septal reduction therapy(SRT)cohort and the non-SRT cohort.The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death.Outcome analyses were conducted to evaluate the associations between HT and outcomes in HCM.Medications before enrollment and at discharge were collected in the post-hoc analyses.RESULTS HCM patients without HT were younger,had a lower body mass index,were more likely to have a family history of HCM,and had a smaller left ventricular(LV)end-diastolic diameter than those with HT in both cohorts.A thicker LV wall,a higher level of N-terminal pro-B-type natriuretic peptide,and a higher extent of LV late gadolinium enhancement were additionally observed in patients without HT in the non-SRT cohort.The presence of HT did not alter the distribution pattern of late gadolinium enhancement,as well as the constituent ratio of eight disease-causing sarcomeric gene variants in both cohorts.Outcome analyses showed that in the non-SRT cohort,patients without HT had higher risks of cardiovascular death(HR=2.537,P=0.032)and all-cause death(HR=3.309,P=0.032).While such prognostic divergence was not observed in the SRT cohort.Further post-hoc analyses in the non-SRT cohort found that patients without HT received fewer non-dihydropyridine calcium channel blockers and angiotensinconverting enzyme inhibitors/angiotensin receptor blockers before enrollment and at discharge.CONCLUSIONS HCM patients without HT had worse clinical conditions and higher mortality than patients with HT overall,which may result from active medical therapy in HT patients.Active SRT may have a substantial de-risking effect on patients meeting the indications.

Unveiling shared genetic pathways in cardiovascular diseases:towards personalized therapies and holistic treatment approaches

Cardiovascular diseases(CVDs),encompassing diverse pathologies such as atherosclerosis,hypertension,cardiomyopathy,arrhythmia,and valvular diseases,represent a significant public health challenge,severely undermining human health[1].According to the World Health Organization,CVDs claimed approximately 17.9 million deaths in 2019,representing 32%of all global deaths[2,3].The risk of CVDs morbidity and mortality increases with age,with the majority of CVDs and deaths occurring in elderly aged 75 years and older[4,5].In developed nations,CVDs are the principal cause of mortality,while in developing countries,they are a leading cause of death as well.

Exploring non-invasive diagnostics for metabolic dysfunctionassociated fatty liver disease

The population with metabolic dysfunction-associated fatty liver disease(MAFLD)is increasingly common worldwide.Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care.Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD,but it has associated risks and limitations.This has spurred the exploration of non-invasive diagnostics for MAFLD,especially for steatohepatitis and fibrosis.These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements,serum tests,imaging or stool metagenome profiling.However,they still need rigorous and widespread clinical validation for the diagnostic performance.

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa.First,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression.In particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

Application of microfluidic chip technology in pharmaceutical analysis:A review

The development of pharmaceutical analytical methods represents one of the most significant aspects of drug development. Recent advances in microfabrication and microfluidics could provide new approaches for drug analysis, including drug screening, active testing and the study of metabolism. Microfluidic chip technologies, such as lab-on-a-chip technology, three-dimensional (3D) cell culture, organs-on-chip and droplet techniques, have all been developed rapidly. Microfluidic chips coupled with various kinds of detection techniques are suitable for the high-throughput screening, detection and mechanistic study of drugs. This review highlights the latest (2010–2018) microfluidic technology for drug analysis and discusses the potential future development in this field.

Validation of the Simplified Chinese-character Version of the International Physical Activity Questionnaire-Long Form in Urban Community-dwelling Adults:a Cross-sectional Study in Hangzhou,China

Objective To assess the test-retest reliability and criterion validity of the Simplified Chinese-character version of the International Physical Activity Questionnaire Long form （IPAC）.-L） in urban community-dwelling adults in Hanghzou, China. Methods A total of 158 eligible participants aged 25-59 years from 6 neighbourhoods in two central districts of Hangzhou completed the IPAQ-L questionnaire twice within a 7-day interval. Half of the subjects wore pedometers during the first 7 days. Test-retest reliability was examined by comparing the first （Day 1） and the second （Day 9） survey of IPAQ-L Criterion validity was assessed by comparing IPAO,-L with pedometer data. Results Modest to good test-retest reliability was found with intraclass correlation coefficients of 0.67 for total PA, 0.37 to 0.73 for specific dimensions, and 0.56 to 0.71 for different intensities of PA. Total PA measured by IPAO.-L was moderately correlated with exercise levels （partial r = 0.27, P = 0.020） and walking distance （partial r = 0.31, P = 0.007）, which were measured by a pedometer, after adjusting for gender, age, educational attainment and employment status. Conclusion Our results indicate that the IPAO.-L is a reliable and validated measure for assessing physica activity levels in this population and possibly the adult population in other mainland Chinese cities.

Risk factors of distal segment aortic enlargement after complicated type B aortic dissection

Objectives:Distal segment aortic enlargement(DSAE)is a common complication that influences the long-term prognosis of type B aortic dissection(TBAD)after thoracic endovascular aortic repair(TEVAR).In this study,a multivariate analysis was performed to find potential factors predictive of DSAE.Methods:A single-center retrospective study was performed from 1999 to 2016.Included in the study were complicated TBAD patients who underwent TEVAR with uncovered residual tears.Based on the diameter of the distal segment of the uncovered aorta,we assigned patients to an enlargement group and a non-enlargement group.Data extracted from the medical records included demographic and clinical characteristics and followup computed tomography angiography data.The primary endpoints were the all-cause mortality and the presumably aortic-related events that required reintervention during the follow-up period.Results:For the 333 patients,all-cause mortality was 38(11.41%),and 76(22.82%)patients underwent reintervention.A total of 70(21.02%)patients experienced DSAE,among them were 2 patients who died of aortic rupture and 58 patients who accepted reintervention.Multivariate analysis reviewed independent risk factors of postoperative DSAE,including current smoking,the residual length of the patent false lumen,the postoperative number of dissection tears in the thoracic aorta and type III aortic arch;as well as protective factors,including the application of a restrictive bare stent(RBS),the length of covered stent in the descending thoracic aorta,and the distance from the residual first tear to the left subclavian artery(LSA).Conclusion:DSAE after TEVAR for patients with a complicated TBAD can be influenced by their current smoking habit,the residual length of patent false lumen,the postoperative number of dissection tears in the thoracic aorta and the aortic arch type.Meanwhile,RBS usage,the length of the covered stent in the descending thoracic aorta and the distance from the residual first tear to the LSA could have positive effect on the prognosis.

Association between body mass index and the risk of bleeding in elderly patients with non-valvular atrial fibrillation taking dabigatran:a cohort study

Background Uncertainty remains regarding the association between body mass index(BMI)and the risk of bleeding in patients with non-valvular atrial fibrillation(NVAF).We aimed to investigate the association between BMI and the risk of bleeding in elderly NVAF patients taking dabigatran.Methods A total of 509 elderly NVAF patients,who were being treated at twelve centers in China from February 2015 to December 2017 and taking dabigatran,were analyzed.The exposure and outcome variables were BMI at baseline and bleeding events within the subsequent six months,respectively.Cox proportional hazards regression analysis was used to evaluate the association between BMI and the risk of bleeding.Moreover,the Cox proportional hazards regression with cubic spline functions and smooth curve fitting was conducted.Results During the six-month follow-up,50 participants experienced bleeding.Every 1 kg/m^2 increase in BMI was associated with a 12%increased risk of bleeding(P=0.021).Compared to those with BMI values in Tertile 1(<22.5 kg/m^2),the adjusted hazard ratio(HR)of bleeding for participants in Tertile 2(22.5–25.3 kg/m^2)and Tertile 3(>25.3 kg/m^2)were 2.71(95%CI:1.02–7.17)and 3.5(95%CI:1.21–8.70),respectively.The Ptrend-value was significant in all models.The adjusted smooth curve showed a linear association between BMI and bleeding.None of the stratified variables showed significant effect modification on the association between BMI and bleeding(Pinteraction>0.05).Conclusions BMI was significantly and positively associated with the risk of bleeding in elderly NVAF patients treated with dabigatran.

Efficacy of Short-term Dual Antiplatelet Therapy after Implantation of Second-generation Drug-eluting Stents:A Meta-analysis and Systematic Review

Objective The benefit of short-term dual antiplatelet therapy(DAPT) following second-generation drug-eluting stents implantation has not been systematically evaluated. To bridge the knowledge gap,we did a meta-analysis to assess the efficacy of ≤6 months versus ≥12 months DAPT among patients with second-generation drug-eluting stents. Methods We searched online databases and identified randomized controlled trials that assess the clinical impact of short-term DAPT(≤6 months) published before March 3,2016. The efficacy endpoints included the incidence of all-cause death,myocardial infarction,cerebrovascular accidents,and definite or probable stent thrombosis. Safety endpoint defined as major bleeding was also evaluated and discussed. Results We included 5 trials that randomized 9473 participants(49.8%,short-term DAPT duration vs. 50.2%,standard duration). A total of 9445(99.7%) patients reported the efficacy endpoints,and the safety endpoint was available from 4 studies(n=8457). There was no significant difference in efficacy endpoints between short-term and standard DAPT duration(≥12 months) [risk ratio(RR) 0.96; 95% confidence intervals(CI),0.80-1.15]. Short-term DAPT duration did not significantly increase the individual risk of all-cause death,myocardial infarction,cerebrovascular accidents,or definite or probable stent thrombosis. Although short-term DAPT obviously reduced risk of major bleeding compared with standard DAPT(RR 0.53; 95% CI,0.29-0.96),significant publication bias was found when accessing the safety endpoint of the 4 studies(Egger's test,P=0.009). Conclusions The efficacy of short-term DAPT was comparable with that of standard duration DAPT.DAPT less than 6 months may be appropriate for patients receiving second-generation drug-eluting stents implantation.

Effective extraction of fluoroquinolones from water using facile modified plant fibers

In this study,ecofriendly and economic carboxy-terminated plant fibers(PFs)were used as adsorbents for the effective in-syringe solid phase extraction(IS-SPE)of fluoroquinolone(FQ)residues from water.Based on the thermal esterification and etherification reaction of cellulose hydroxy with citric acid(CA)and sodium chloroacetate in aqueous solutions,carboxy groups grafted onto cotton,cattail,and corncob fibers were fabricated.Compared with carboxy-terminated corncob and cotton,CA-modified cattail with more carboxy groups showed excellent adsorption capacity for FQs.The modified cattail fibers were reproducible and reusable with relative standard deviations of 3.2%-4.2% within 10 cycles of adsorptiondesorption.A good extraction efficiency of 71.3%-80.9% was achieved after optimizing the extraction condition.Based on carboxylated cattail,IS-SPE coupled with ultra-performance liquid chromatography with a photodiode array detector was conducted to analyze FQs in environmental water samples.High sensitivity with limit of detections of 0.08-0.25 mg/L and good accuracy with recoveries of 83.8%-111.7% were obtained.Overall,the simple and environment-friendly modified waste PFs have potential applications in the effective extraction and detection of FQs in natural waters.

First Results of ACH Cardioplegic Solution Clinical Application in Newborns and Infants under One Year of Age

Study objective involved comparison of two cardioplegic solutions: HTK-solution possessing high buffer capacity and a new ACH-solution with aminoacid buffer. Results revealed high cardioprotective efficiency during surgical repair of complex congenital heart disease both in the group that had received Custodiol and in the group that had received ACH-solution. Clinical and morphological parameters demonstrate high level of myocardial protection from intraoperative ischemia for single usage of ACH-solution during cardioplegic ischemia under 60 minutes in duration.

The underground organ microbial complexes of moorland spotted orchid <i>Dactylorhiza maculata</i>(L.) Soó(Orchidaceae)

This paper is focused on the first study of microbiota of a moderate climate orchid from Northern hemisphere—Moorland Spotted Orchid Dactylorhiza maculata (L.) Soó growing in its natural habitat. There have been obtained detailed data concerning bacterial communities from rhizosphere and inner tissues of young and old tubers. It was done using the biomarker analysis method where the markers were detected by gas chromatography—mass-spectrometry. It is shown that the number of bacterial genera and the bacteria amount (105 - 108 CFU per gram of dry weight) in D. maculata microbial complexes decreases from rhizosphere to old tuber to young. At the same time all three bacterial cenoses closely resemble each other in biodiversity. Their constant members are gg. Hyphomicrobium, Methylococcus, Nitrobacter, Pseudomonas and Sphingomonas (Proteobacteria), Bacillus and Clostridium (Firmicutes), Rhodococcus and Streptomyces (Actinobacteria). There were found differences peculiar to the taxonomic structure of each microbial complex. The rhizosphere is dominated by Actinobacteria while in inner tissues Proteobacteria are prevalent. The bacteria of gg. Ochrobactrum, Xanthomonas, Butyrivibrio, Corynebacterium, Mycobacterium, Propionibacterium, Sphingobacterium and specific iron reducers were shown to belong to rhizosphere community. Genera of Agrobacterium and Bifidobacterium were found only in the endophytic microbiota of the young tuber while g. Aeromonas

A Case Report of Cardiac Amyloidosis Presenting with Chest Discomfort

Introduction: Cardiac amyloidosis is one of the several systemic manifestations of amyloidosis. It is a relatively uncommon disease. Patients with cardiac amyloidosis clinically present with rapidly progressive heart failure. Case Presentation: We present a case of 64-year-old man with multiple episodes of chest discomfort accompanied sometimes with dyspnoea for the past several months. A non-specific ST-T changes with low voltage limb leads on ECG, a diastolic dysfunction with preserved ejection fraction on echocardiography, increased troponin and BNP, increased serum λ/κ light chain ratio led us to highly suspect amyloidosis with cardiac involvement. Abdominal fat pad biopsy confirmed the amyloid type change of subcutaneous fat, with immunohistochemistry revealing Lambda positive. After confirmed diagnosis of primary systemic amyloidosis with cardiac involvement, patient completed six cycles of chemotherapy with bortezomib and dexamethasone. The patient showed significant improvements after chemotherapy and supportive therapy. Conclusion: Amyloidosis is relatively fatal disease. Patients often have a short life expectancy after symptom onset. Early diagnosis is crucial to proper management and better prognosis.