Effect of probiotics on children with autism spectrum disorders: a meta-analysis.

BACKGROUND: Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children. METHODS: The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index). RESULTS: In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children. CONCLUSION: Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.

[Research Progress of High-intensity Interval Training in Cardiac Rehabilitation of Patients with Acute Coronary Syndrome].

Acute coronary syndrome (ACS),with increasing mortality year by year,has become a major public health problem in China.Exercise rehabilitation as an important part of the out-of-hospital rehabilitation for the patients with heart diseases can further reduce the mortality of patients on the basis of drug treatment.The available studies have proved that high-intensity interval training (HIIT) is more effective and efficient than moderate-intensity continuous training (MICT) such as walking and jogging on chronic cardiovascular diseases such as heart failure,stable coronary heart disease,and hypertension and has high security.According to the latest research,HIIT can reduce the platelet response,mitigate myocardial ischemia-reperfusion injury,and increase the exercise compliance of ACS patients more significantly than MICT.Moreover,it does not increase the risk of thrombotic adverse events or malignant arrhythmia.Therefore,HIIT is expected to become an important part of exercise prescription in out-of-hospital cardiac rehabilitation strategy for the patients with ACS.

Ginsenoside Rh2 attenuates myocardial ischaemia­reperfusion injury by regulating the Nrf2/HO­1/NLRP3 signalling pathway.

Ginsenoside Rh2 (GRh2) is a monomer isolated from red ginseng that has extensive pharmacological effects. However, whether GRh2 has a protective effect on ischaemia/reperfusion (I/R) in the myocardium has yet to be elucidated. The present study aimed to identify the anti-inflammatory and antioxidant effects of GRh2 on I/R in the myocardium and its underlying mechanism. A rat model of myocardial I/R injury was constructed by ligating the left anterior descending coronary artery, which was subsequently treated with GRh2. A total of 40 male Sprague-Dawley rats were divided into the following four groups: The sham group, the I/R group, the I/R+GRh2 (10 mg/kg) group and the I/R+GRh2 (20 mg/kg) group. Neonatal rat cardiomyocytes were also used to evaluate the protective effect of GRh2 on hypoxia/reoxygenation (H/R)-induced myocardial injury in vitro. The GRh2 pre-treatment reduced the I/R- or H/R-induced release of myocardial enzymes and the production of IL-1ß, IL-18 and TNF-α. GRh2 reduced the area of myocardial infarction and the histological changes in the myocardium and improved cardiac functions. In addition, GRh2 reduced the expression levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein, caspase-1, malondialdehyde and reactive oxygen species and increased the expression levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase and superoxide dismutase. In conclusion, the present study confirmed that GRh2 could reduce oxidative stress and inflammation in cardiomyocytes after reperfusion, and its mechanism of action may be related to its regulation of the Nrf2/HO-1/NLRP3 signalling pathway.

Efficacy and safety of genotype-guided antiplatelet therapy versus standard treatment in 4,604 patients with CAD after PCI: a meta-analysis of randomized controlled trials.

Objective: To compare the efficacy and safety of genotype-guided antiplatelet strategy and standard treatment in patient with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Methods: Relevant studies published in Medline, Embase, CoChrane Library were searched for randomized controlled trials (RCTs) until August 2020. Studies were screened by selection criteria, quality assessed using the Cochrane Collaboration's tool. Data were extracted from the included studies and statistically analyzed by RevMan 5.3 software. Results: Four RCTs involving 4,604 patients were included in this meta-analysis. Compared with the standard treatment group, the pooled results showed that genotype-guided group associated with lower risk of major adverse cardiovascular events (MACE, OR=0.52, 95%CI:0.35-0.78, P =0.001), any bleeding (OR=0.77, 95%CI: 0.62-0.95, P =0.02) and myocardial infarction (MI, OR=0.48, 95%CI:0.33-0.68, P <0.0001). There was no significant difference in death of any cause (OR=0.53, 95%CI: 0.18-1.54, P =0.25), cardiovascular death (OR=0.74, 95%CI:0.48-1.14, P =0.17), target vessel revascularization (OR=0.66, 95%CI:0.39-1.12, P =0.12) and major bleeding events (OR=0.86, 95%CI: 0.58-1.28, P =0.47). Conclusion: Genotype guided antiplatelet therapy could reduce the risk of MACE, MI and any bleeding events in patients with CAD undergone PCI, compared with standard treatment. Therefore, the findings support that implementation of genotype testing to tailor antiplatelet therapy after PCI.

Analysis of influencing factors related to elevated serum troponin I level for COVID-19 patients in Yichang, China.

BACKGROUND: Cardiac injury is a common condition among hospitalized coronavirus disease 2019 (COVID-19) patients, and is associated with a higher risk of mortality. However, the mechanism of myocardial injury in COVID-19 remains unclear. In this retrospective study, we compared the clinical characteristics of COVID-19 patients with different troponin I (TnI) levels during hospitalization to provide a clinical reference for the identification of those at high-risk. METHODS: In total, 218 patients diagnosed with COVID-19 in Yichang Central People's Hospital and Yichang Third People's Hospital between January 23 and February 19, 2020 were initially included. Of these patients, 89 underwent TnI testing during hospitalization and were finally included in the study. The medical history, clinical signs and symptoms at the time of admission, and laboratory test results were recorded. The patients were assigned to the normal TnI group (TnI <0.01 µg/L; n=67) or the elevated TnI group (TnI >0.01 µg/L; n=22). RESULTS: The incidence of elevated TnI in our patient cohort was 24.7%. There were significant differences between the two groups in the following factors: history of coronary heart disease (CHD), age, lymphocyte count, prothrombin time (PT), activated partial thromboplastin time (APTT), and levels of interleukin (IL)-6, C-reactive protein (CRP), myoglobin (MYO), lactate dehydrogenase (LDH), and albumin (all P<0.05). Binary logistic analysis showed that a history of CHD, age, lymphocyte count, IL-6, APTT, and MYO were influencing factors of elevated serum TnI. CONCLUSIONS: A history of CHD, advanced age, decreased lymphocyte count, increased IL-6, increased MYO, and prolonged APTT were independent influencing factors of elevated TnI in COVID-19 patients. COVID-19 patients with these characteristics are prone to myocardial injury.

Duration of dual antiplatelet therapy after percutaneous coronary intervention with implantation of second-generation drug-eluting stent: A meta-analysis of randomized controlled trials.

Objective: The optimal duration of dual antiplatelet therapy (DAPT) in patients after PCI with implantation of a drugeluting stent is still controversial. We conducted a meta-analysis to compare the efficacy and safety of short term DAPT (≤ 3 months) followed by P2Y12 inhibitor monotherapy and standard DAPT (12 months) after PCI. Method: Relevant studies published in Medline, Embase, CoChrane Library were searched for randomized controlled trials (RCTs) until November 2019. Studies were screened by selection criteria then quality assessed through the Cochrane Collaboration's tool. Data were extracted from the included studies and statistically analyzed by RevMan 5.3 software. Results: Five RCTs (n=18,357) were included. Compared with standard DAPT, the short term DAPT was associated with a significant decrease in the major bleeding [odds ratio (OR)=0.43, 95% Confidence Interval (CI):0.32-0.58, P <0.00001] and any bleeding [OR=0.56, 95%CI:0.47-0.66, P<0.00001]. There were no significant differences in all-cause death [OR=0.91, 95%CI:0.71-1.16, P =0.45], major adverse cardiac and cerebrovascular event [OR=1.01, 95%CI:0.87-1.17, P =0.91] and stent thrombosis [OR=0.97, 95%CI:0.61-1.54, P =0.91] between with the short term DAPT group and the standard DAPT group. Conclusions: Short term DAPT followed by P2Y12 monotherapy could reduce the risk of bleeding without increasing the incidence of ischemic events after PCI with implantation of second-generation DES compared with standard DAPT. Therefore, short term DAPT may be a promising strategy to balance ischemic events and bleeding complications in patients after PCI.

Inhibition of microRNA-327 ameliorates ischemia/reperfusion injury-induced cardiomyocytes apoptosis through targeting apoptosis repressor with caspase recruitment domain.

Apoptosis is the major cause of cardiomyocyte death in myocardial ischemia/reperfusion injury (MI/RI). Increasing evidence suggests that microRNAs (miRNAs) can contribute to the regulation of cardiomyocytes apoptosis by posttranscriptional modulation of gene expression networks. However, the effects of miR-327 in regulating MI/RI-induced cardiomyocytes apoptosis have not been extensively investigated. This study was performed to test whether miR-327 participate in cardiomyocytes apoptosis both in vitro and in vivo, and reveal the potential molecular mechanism of miR-327 regulated MI/RI through targeting apoptosis repressor with caspase recruitment domain (ARC). Sprague-Dawley (SD) rats were subjected to MI/RI by left anterior descending coronary artery occlusion for 30 min and reperfusion for 3 hr. H9c2 cells were exposed to hypoxia for 4 hr and reoxygenation for 12 hr to mimic I/R injury. miRNA-327 recombinant adenovirus vectors were transfected into H9c2 cells for 48 hr and rats for 72 hr before H/R and MI/RI treatment, respectively. The apoptosis rate, downstream molecules of apoptotic pathway, and the target reaction between miRNA-327 and ARC were evaluated. Our results showed that miR-327 was upregulated and ARC was downregulated in the myocardial tissues of MI/RI rats and in H9c2 cells with H/R treatment. Inhibition of miR-327 decreased the expression levels of proapoptotic proteins Fas, FasL, caspase-8, Bax, cleaved caspase-9, cleaved caspase-3, and the release of cytochrome-C, as well as increasing the expression levels of antiapoptotic protein Bcl-2 via negative regulation of ARC both in vivo or vitro. In contrast, overexpression miR-327 showed the reverse effect. Moreover, the results of luciferase reporter assay indicated miR-327 targets ARC directly at the posttranscriptional level. Taken together, inhibition of miR-327 could attenuate cardiomyocyte apoptosis and alleviate I/R-induced myocardial injury via targeting ARC, which offers a new therapeutic strategy for MI/RI.

Down-Regulation of miR-327 Alleviates Ischemia/Reperfusion-Induced Myocardial Damage by Targeting RP105.

BACKGROUND/AIMS: Micro RNAs (miRNAs) play a very important role in myocardial ischemia/ reperfusion injury (MIRI), including in inflammation, apoptosis, and angiogenesis. Previous studies have demonstrated up-regulation of miR-327 in renal ischemia/reperfusion injury and MIRI. Via TargetScan, we found RP105 is a possible target gene of miR-327; our previous studies have also confirmed that RP105 acted as a cardioprotective protein in MIRI by reducing inflammation. However, the regulatory effect of miR-327 on RP105 has not previously been proposed. In our study, we aimed to identify the regulatory effect of miR-327 on RP105 protein in MIRI rats. METHODS: Sixty male Sprague-Dawley rats were randomly divided into five groups, which were pre-treated with saline (sham and ischemia/reperfusion group), adenovirus-expressing miR-327-RNAi (Ad-miR-327-i group), control (Ad-NC group), or pri-miR-327 (Ad-miR-327 group) treatments. Three days later, the rat MIRI model was established by ischemia for 30 min, followed by reperfusion for 3 h. Myocardium and plasma were harvested and assessed. RESULTS: miR-327 was increased by nearly 3-fold both in myocardium and plasma, which down-regulated RP105 in a 3'-untranslated region-dependent manner, and down-regulation of miR-327 via adenovirus transfection indirectly suppressed the TLR4/ TLR2-MyD88-NF-κB signaling axis activation via up-regulation of RP105, which subsequently resulted in reduced myocardial infarct size, attenuated cardiomyocyte destruction, and alleviated inflammation. In contrast, up-regulation of miR-327 induced the opposite effect. CONCLUSION: Down-regulation of miR-327 exerts a cardioprotective effect against MIRI by reducing inflammation, which may constitute a promising molecular therapeutic target for treating MIRI.

Vitamin D and new-onset atrial fibrillation: A meta-analysis of randomized controlled trials.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which affects 1.5% to 2% of the general population. More than six million Europeans suffer from AF. To research vitamin D levels in the prevention of new-onset atrial fibrillation (AF), we conducted a systematic review of randomized controlled trials (RCTs). We focused on the vitamin D levels in the prevention of new-onset AF. The outcomes assessed were vitamin D levels, left ventricular ejection fraction (LVEF), and left atrium diameter. Six RCTs ultimately met the inclusion criteria in the meta-analysis. The outcomes of Vitamin D levels (MD = -4.27, 95% CI = -5.20 to-3.34, P = 0.30) in the new-onset AF showed no significant difference. The left atrium diameter (MD = 1.96, 95% CI = 1.48 to 2.60, P < 0.01) between new-onset AF and LVEF (MD = -0.92, 95% CI = -1.59 to -0.26, P < 0.01) showed significant difference. Our study shows that circulating vitamin D levels may not play a major role in the development of new-onset AF.

RNAi-Mediated Down-Regulation of CD47 Protects against Ischemia/Reperfusion-Induced Myocardial Damage via Activation of eNOS in a Rat Model.

BACKGROUND/AIMS: Oxidative stress is strongly implicated in the pathogenesis of myocardial damage caused by ischemia reperfusion (I/R). Previous studies have confirmed that cardiac CD47 drives left ventricular heart failure. However, the role for CD47 in myocardial I/R injury (MIRI) has not previously been proposed. This study was designed to investigate whether down-regulation of CD47 using RNA interference (RNAi) technology can relieve inhibition of nitric oxide signaling and attenuate myocardial damage in a rat model of I/R. METHODS: Male Sprague-Dawley rats (n = 40) were randomly allocated to four groups and pre-treated either with saline (Sham and I/R groups), or adenovirus expressing either control (Ad-EGFP-N) or CD47-targeting (Ad-EGFP-CD47) RNAi. After four days, the rat MIRI model was established by occluding the left anterior descending coronary artery for 30 min, followed by reperfusion for 3 h. Heart tissue was harvested and assessed by immunohistochemistry, western blot, and quantitative RT-PCR. Outcome measures included infarct size, myocardial enzyme (creatine kinase, creatine kinase-MB, and lactate dehydrogenase) levels in serum, markers of oxidative stress, and morphological changes to the myocardium. RESULTS: Delivery of Ad-EGFP-CD47 RNAi into the myocardium remarkably decreased CD47 expression levels. Down-regulation of CD47 was significantly associated with reduced infarct size and serum levels of myocardial enzymes, increased activity of endothelial nitric oxide synthase, increased levels of nitric oxide, and decreased levels of oxidative stress. CONCLUSION: These data indicate that down-regulation of CD47 exerts a protective effect against MIRI, which may be attributable to attenuation of oxidative stress via activation of the eNOS/NO signaling pathway.

Activating transcription factor 3--an endogenous inhibitor of myocardial ischemia-reperfusion injury (Review).

Coronary heart diseases, particularly acute coronary syndrome, have increased in morbidity and mortality in recent decades. Percutaneous coronary intervention, coronary artery bypass grafting and thrombolytic agents are effective strategies to rescue the infarcted myocardium. In addition to acute myocardial infarction, the resulting myocardial ischemia­reperfusion injury (MIRI) leads to serious secondary injury of the heart. Studies have demonstrated that activating transcription factor (ATF)/cyclic adenosine monophosphate response element binding family member ATF3 had a negative regulatory role in IRI, particularly in the kidney, cerebrum and liver. The present review expounded the expression characteristics of ATF3 and its protective effects against MIRI, providing a theoretical basis for the overexpression of ATF3 in the myocardium as a promising gene-therapeutic strategy for MIRI.

A Meta-Analysis of Randomized Clinical Trials Comparing Shorter (Less or Equal Than 6 Months) and Longer (More or Equal Than 12 Months) Dual Anti-Platelet Therapy Following Drug-Eluting Coronary Stents.

CONTEXT: The optimal duration of dual anti-platelet therapy (DAPT) after the implantation of drug-eluting coronary stents (DES) is still the subject of ongoing debate. This meta-analysis was performed to investigate the optimal duration between ≤ 6 months and ≥ 12 months for DAPT after implantation of DES. EVIDENCE ACQUISITION: This study was conducted at the department of cardiology, the first college of clinical medical sciences, institute of cardiovascular diseases of Three Gorges university during December 2014. Pub-med, Cochrane, Scopus and clinicaltrials.gov databases were searched for papers published until December 2014. Searches of the above databases included terms "dual anti-platelet therapy" and "myocardial infarction (MI)" and "drug-eluting stents (DES)". All the searched literatures were limited to Randomized Controlled Trials (RCTs). Quality assessments were evaluated with the Jadad quality scale. Data were extracted by two independent observers (FZ and YC). For all analyses, the 95% confidence interval (CI) was calculated and heterogeneity of the studies was analyzed using I2 statistics. RESULTS: Five RCTs with 9979 participants satisfying the inclusion criteria were finally analyzed. Overall, there were 4993 patients with shorter duration of DAPT and 4986 patients with a longer treatment. Clopidogrel was the used P2Y12 receptor inhibitor in all five RCTs. On one hand compared to shorter duration (≤ 12 months) DAPT, longer duration (≥ 12 months) did not reduce risk of mortality, cardiac death, cerebrovascular accidents, myocardial infarction and stent thrombosis (pooled OR 1.03, 95% Confidence Interval (CI) 0.80 - 1.32, P = 0.85, I(2) = 0%; pooled OR 0.91, 95% CI 0.64 - 1.29, P = 0.60, I(2) = 0%; pooled OR 0.84, 95% CI 0.50 - 1.42, P = 0.51, I(2) = 0%; pooled OR 1.17, 95% CI 0.87 - 1.58, P = 0.29, I(2) = 0%; pooled OR 1.36, 95% CI 0.81 - 2.29, P = 0.24, I(2) = 0%). On the other hand, longer duration (≥ 12 months) could also increase the risk of thrombolysis in myocardial infarction (TIMI) major bleeding (pooled OR 0.50, 95% CI 0.29 - 0.85, P = 0.01, I(2) = 0%). CONCLUSIONS: Regarding the efficacy outcomes of the patients after DES implantation, no differences were found between shorter (≤ 6 months) and longer (≥ 12 months) duration of DAPT. What is worse is that longer duration (≥ 12 months) was associated with increased risk of bleeding complications.

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4-Mediated Signaling Pathways.

BACKGROUND: Myocardial apoptosis is heavily implicated in the myocardial damage caused by ischemia-reperfusion (I/R). Toll-like receptor 4 (TLR4) is a potent inducer of these apoptotic cascades. In contrast, the radioprotective 105 kDa protein (RP105) is a specific negative regulator of TLR4 signaling pathways. However, the precise mechanisms by which RP105 inhibits myocardium apoptosis via TLR4-associated pathways during I/R is not fully understood. METHODS: We utilized a rat model of myocardial ischemic reperfusion injury (MIRI). Animals were pre-treated with Ad-EGFP adenovirus, Ad-EGFP-RP105 adenovirus, saline, or nothing (sham). After three days, rats underwent a 30min left anterior descending coronary artery occlusion and a 4h reperfusion. Mycardial tissue was assessed by immunohistochemistry, TUNEL-staining, Western blot, quantitative RT-PCR, and a morphometric assay. RESULTS: RP105 overexpression resulted in a reduction in infarct size, fewer TUNEL-positive cardiomyocytes, and a reduction in mitochondrial-associated apoptosis cascade activity. Further, RP105 overexpression repressed I/R-induced myocardial injury by attenuating myocardial apoptosis. This was mediated by inhibiting TLR4 activation and the phosphorylation of P38MAPK and the downstream transcription factor AP-1. CONCLUSION: RP105 overexpression leads to the de-activation of TLR4, P38MAPK, and AP-1 signaling pathways, and subsequently represses apoptotic cascades and ensuing damage of myocardial ischemic reperfusion. These findings may become the basis of a novel therapeutic approach for reducing of cardiac damage caused by MIRI.