Remote cyclic compression ameliorates myocardial infarction injury in rats via AMPK-dependent pathway.

BACKGROUND: Remote ischemic conditioning (RIC) displays a cardioprotective role in acute myocardial infarction (AMI). Since interruption of blood vessel is not an essential trigger of remote cardioprotection, tissue compression may play a prominent part in the effect. The purpose of this study was to confirm the protective effect of tissue compression on AMI and the underlying mechanisms. METHODS AND RESULTS: Rat model of AMI was induced by ligation of the left anterior descending coronary artery. Remote cyclic compression (RCC) on forelimb was applied to AMI rats for 3 days after the operation. RCC postconditioning displayed cardioprotective effects against AMI injury by limiting infarct size, alleviating cardiac dysfunction, and suppressing cardiomyocyte apoptosis. In addition, RCC postconditioning induced myocardial autophagy as evidenced by increased LC3-II and Beclin-1 and reduced mTOR levels. Furthermore, RCC treatment upregulated AMPK phosphorylation in the context of AMI hearts. AMPK inhibitor Compound C administration markedly abrogated RCC-mediated cardioprotective effect, as evidenced by decreased infarct size and cardiac function. CONCLUSION: Our results indicated that RCC postconditioning could attenuate AMI injury through inhibiting apoptosis and promoting autophagy via AMPK signaling pathway. The research provided a novel perspective for studying the cardioprotection of RIC and possible therapeutic strategy for managing AMI injury.

Effect of injection of different doses of isoproterenol on the hearts of mice.

BACKGROUND: Heart failure (HF) is one of the diseases that seriously threaten human health today and its mechanisms are very complex. Our study aims to confirm the optimal dose ISO-induced chronic heart failure mice model for better study of HF-related mechanisms and treatments in the future. METHODS: C57BL/6 mice were used to establish mice model of chronic heart failure. We injected isoproterenol subcutaneously in a dose gradient of 250 mg/kg, 200 mg/kg, 150 mg/kg, 100 mg/kg and 50 mg/kg. Echocardiography and ELISA were performed to figure out the occurrence of HF. We also supplemented the echocardiographic changes in mice over 30 days. RESULTS: Except group S and group E, echocardiographic abnormalities were found in other groups, suggesting a decrease in cardiac function. Except group S, myofibrolysis were found in the hearts of mice in other groups. Brain natriuretic peptide was significantly increased in groups B and D, and C-reactive protein was significantly increased in each group. CONCLUSION: Our research finally found that the HFrEF mice model created by injection at a dose of 100 mg/kg for 7 days was the most suitable and a relatively stable chronic heart failure model could be obtained by placing it for 21 days.

Electroacupuncture interventions alleviates myocardial ischemia reperfusion injury through regulating gut microbiota in rats.

Electroacupuncture (EA) intervention has a remarkable cardioprotection against myocardial ischemia reperfusion injury (MIRI). Recently, it has been suggested that the gut microbiota plays an important role in regulating the progression and prognosis of MIRI. The purpose of this study was to illustrate the relationship between gut microbiota and cardioprotection of EA on MIRI. We conducted a MIRI model by ligating the left anterior descending coronary artery for 30 min followed by reperfusion in male Sprague Dawley rats, which then received 7 days of EA intervention. Echocardiography was employed to evaluate left ventricular function. Fecal samples were collected for microbial analysis by 16S rDNA high-throughput sequencing. Blood samples and myocardium were collected for inflammatory cytokine detection by enzyme linked immunosorbent assay (ELISA) and Western blot. Hematoxylin & eosin (HE) staining and immunofluorescence of ileum tissue were performed for intestinal damage evaluation. After 7 days of EA intervention, the left ventricular function was improved with significantly increased ejection fraction and fractional shortening. Furthermore, we found that EA intervention reversed the changed gut microbiota induced by MIRI, including Clostridiales, RF39, S24-7, Desulfovibrio, and Allobaculum, improved the impaired gut barrier, reduced the production and circulation of lipopolysaccharide (LPS), inhibited the level of interleukin 6 (IL-6) and interleukin 12 (IL-12) in periphery and decreased the expression of Toll like receptor 4 (TLR4) and IL-6 in myocardium. EA intervention could improve the impaired gut mucosal barrier and reduce the production and circulation of LPS after MIRI through regulating gut microbiota, thus inhibiting the circulation and myocardium inflammation and finally exerted the cardioprotective effect.

Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis.

INTRODUCTION: Soluble suppression of tumorigenicity-2 (sST2) has been considered as a prognostic factor of cardiovascular disease. However, the prognostic value of sST2 concentration in chronic heart failure remains to be summarized. METHODS: We searched PubMed, Embase, and Web of Science for eligible studies up to January 1, 2020. Data extracted from articles and provided by authors were used in agreement with the PRISMA statement. The endpoints were all-cause mortality (ACM), cardiovascular mortality (CVM)/heart failure-related hospitalization (HFH), and all-cause mortality (ACM)/heart failure-related readmission (HFR). RESULTS: A total of 11 studies with 5,121 participants were included in this analysis. Higher concentration of sST2 predicted the incidence of long-term ACM (hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 1.02-1.04), long-term ACM/HFR (HR: 1.42, CI: 1.27-1.59), and long-term CVM/HFH (HR: 2.25, CI: 1.82-2.79), regardless of short-term ACM/HFR (HR: 2.31, CI: 0.71-7.49). CONCLUSION: Higher sST2 concentration at baseline is associated with increasing risk of long-term ACM, ACM/HFR, and CVM/HFH and can be a tool for the prognosis of chronic heart failure.

[Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine].

Long non-coding RNAs(lncRNAs) and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells. LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion. Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a) or promote autophagy(including MALAT1,miR-152 and miR-24). The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity. In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM) such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo. The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs) as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans. In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway. In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs) is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.

Efficacy and Safety of Acupuncture for Essential Hypertension: A Meta-Analysis.

BACKGROUND The aim of this study was to assess the efficacy and safety of acupuncture therapy for patients with hypertension. MATERIAL AND METHODS We searched PubMed, Embase, the Cochrane Library, the Chinese Biomedical Literature Database, the Chinese National Knowledge Infrastructure, and the Wan-fang Data Database from inception through 29 April 2017. Randomized controlled trials investigating acupuncture therapy for hypertension were included. Review Manager 5.3 software was used for the data analysis. RESULTS A total of 30 RCTs involving 2107 patients were included. The overall methodological quality of the included studies was low. Pooled results demonstrate that acupuncture plus anti-hypertensive drugs is better than anti-hypertensive drugs alone at reducing systolic and diastolic blood pressure (SBP and DBP). The same result was observed for pooled data from experiments that compared acupuncture plus medication to sham acupuncture plus medication at reducing SBP and DBP. However, studies reveal that using acupuncture alone or anti-hypertensive drugs alone do not differ in the effect on lowering blood pressure. Similarly, acupuncture alone also did not differ from sham acupuncture alone, and electroacupuncture versus anti-hypertensive drugs was not significantly different at reducing SBP and DBP. CONCLUSIONS Our systematic review indicates there is inadequate high quality evidence that acupuncture therapy is useful in treating hypertension, as the exact effect and safety of acupuncture therapy for hypertension is still unclear. Therefore, research with larger sample sizes and higher-quality RCTs is still needed.

[Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].

Aging is a gradual process during the loss of functions in cells,organs and tissues by time. The molecular mechanisms of aging-related theories include the classical ones such as telomere,oxygen radical and nonenzymatic glycosylation,as well as the newly proposed ones such as DNA methylation,mitochondrial DNA （mtDNA）and autophagy. The latest study showed the anti-aging effect of autophagy in hematopoietic stem cells. In recent years,based on the molecular regulative mechanisms of aging,a number of the promising anti-aging drugs have been found,including nicotinamide mononucleotide（NMN）and FOXO4-DRI,a peptide of anti-aging. In addition,there are many new discoveries in the field of plant extracts,in which,the extracts from Chinese herbal medicine（CHM）,some single CHMs and the classical prescriptions of CHM,represented by curcumin and resveratrol,have the partial anti-aging effects by regulating the molecular mechanisms of aging both in vivo and in vitro. In brief,developing or exploring anti-aging drugs,especially the natural drugs,is one of the main development directions in the field of anti-aging research in the basis of the molecular regulative mechanisms of aging.

[Electroacupuncture promotes angiogenesis in MIRI rats by modulating the AMPK/KLF2 signaling pathway]. / ç”µé’ˆè°ƒæŽ§è ºè‹·é ¸æ´»åŒ–è›‹ç™½æ¿€é ¶/Kruppelæ ·å› å­2ä¿¡å·é€šè·¯ä¿ƒè¡€ç®¡æ–°ç”Ÿå‡è½»å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒè‚ŒæŸä¼¤.

OBJECTIVES: To observe the effect of electroacupuncture(EA) on adenosine 5'-monophosphate-activated protein kinase (AMPK)/Kruppel-like factor 2 (KLF2) signaling pathway in ischemic myocardial tissues of rats, so as to explore the underlying mechanism of EA in attenuating myocardial ischemia-reperfusion injury (MIRI) through mediating angiogenesis. METHODS: Male SD rats were randomly divided into sham operation group, model group and EA group, with 10 rats in each group. The MIRI model was established by ligation of the anterior descending branch of the left coronary artery. Twenty-four hours after modeling, the rats in the EA group were given EA (2 Hz/100 Hz, 2 mA) at "Neiguan" (PC6) for 20 min each time, once a day for 5 consecutive days. Echocardiography was used to detect cardiac ejection fraction (EF) to evaluate cardiac function. HE staining was used to observe the morphological changes in rat myocardial tissue. Immunohistochemistry was used to detect the density of neovascularization in rat ischemic myocardium. Western blot and ELISA were used to detect the phosphorylated(p)-AMPK, AMPK, KLF2, vascular endothelial growth factor (VEGF) protein expression levels, and VEGF receptor 2 (VEGFR2) content in rat ischemic myocardial tissue, respectively. RESULTS: After modeling, compared with the sham operation group, rats in the model group had decreased EF(P<0.01), significant myocardial fiber damage with inflammatory cell infiltration, increased neovascular density (P<0.05), increased p-AMPK, AMPK, VEGF protein expression levels and VEGFR2 content in myocardial ischemic tissues(P<0.05, P<0.01), and decreased protein expression level of KLF2 (P<0.05). After EA intervention, compared with the model group, rats in the EA group had elevated EF(P<0.01), significantly reduced myocardial fiber damage, reduced inflammatory cell infiltration, increased neovascular density(P<0.01), and elevated p-AMPK, AMPK, KLF2, and VEGF protein expression levels and VEGFR2 content in the myocardial ischemic tissue (P<0.01). CONCLUSIONS: EA may promote angiogenesis, attenuate myocardial injury, and achieve cardioprotective effects in MIRI rats by regulating the expression of AMPK/KLF2 signaling pathway in myocardial tissues.

Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury. / ç”µé’ˆå¯¹å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒå®¤ç»“æž„å’ŒåŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. METHODS: Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1ß and IL-18 were detected by Western blot. RESULTS: In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1ß and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1ß and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. CONCLUSIONS: EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

[Lidong needling therapy combined with functional exercise in treatment of upper limb lymphedema after breast cancer surgery: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise. METHODS: A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated. RESULTS: After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01). CONCLUSION: Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.

Emerging role of substance and energy metabolism associated with neuroendocrine regulation in tumor cells.

Cancer is the second most common cause of mortality in the world. One of the unresolved difficult pathological mechanism issues in malignant tumors is the imbalance of substance and energy metabolism of tumor cells. Cells maintain life through energy metabolism, and normal cells provide energy through mitochondrial oxidative phosphorylation to generate ATP, while tumor cells demonstrate different energy metabolism. Neuroendocrine control is crucial for tumor cells' consumption of nutrients and energy. As a result, better combinatorial therapeutic approaches will be made possible by knowing the neuroendocrine regulating mechanism of how the neuroendocrine system can fuel cellular metabolism. Here, the basics of metabolic remodeling in tumor cells for nutrients and metabolites are presented, showing how the neuroendocrine system regulates substance and energy metabolic pathways to satisfy tumor cell proliferation and survival requirements. In this context, targeting neuroendocrine regulatory pathways in tumor cell metabolism can beneficially enhance or temper tumor cell metabolism and serve as promising alternatives to available treatments.

Electroacupuncture preconditioning protects against myocardial ischemia-reperfusion injury by modulating dynamic inflammatory response.

Background: The protective effects of electroacupuncture (EA) preconditioning against myocardial ischemia-reperfusion injury (MIRI) have been reported. However, the underlying mechanism remains unclear. Recent research has indicated that the dynamic inflammatory response following MIRI plays an essential role in the progression of myocardial injury. This study aimed to investigate the myocardial protective effects of EA preconditioning on MIRI in rats and to explore the relevant mechanism from the perspective of dynamic inflammatory response. Methods: A MIRI model was employed, and the rats were subjected to EA on Neiguan for four days prior to modeling. The myocardial protective effect of EA preconditioning was evaluated by echocardiography, Evans blue and triphenyltetrazolium chloride staining. Real-time polymerase chain reaction, Western blot, hematoxylin & eosin staining, and immunohistochemistry were utilized to detect the content of mitochondrial DNA, NOD receptor family protein 3 (NLRP3) inflammasome activation, neutrophil recruitment and macrophage infiltration in blood samples and myocardium below the ligation. Results: We found that EA preconditioning could accelerate the recovery of left ventricle function after MIRI and reduce the myocardial infarction area, thereby protecting the myocardium against MIRI. Furthermore, EA preconditioning was observed to ameliorate mitochondrial impairment, reduce the level of plasma mitochondrial DNA, modulate NLRP3 inflammasome activation, attenuate neutrophil infiltration, and promote the polarization of M1 macrophages towards M2 macrophages in the myocardium after MIRI. Conclusion: EA preconditioning could reduce plasma mtDNA, suppress overactivation of the NLRP3 inflammasome, facilitate the transition from the acute pro-inflammatory phase to the anti-inflammatory reparative phase after MIRI, and ultimately confer cardioprotective benefits.

[Technical recommendation for pragmatic randomized controlled trial of heat-sensitive moxibustion in community (â ): randomization with consideration of patient preference].

Heat-sensitive moxibustion is the appropriate technique of the external treatment in traditional Chinese medicine and it is widely used in community because of its "easy learning, simple operation and clear curative effect". Pragmatic randomized controlled trial is a main intervention design in the real world study, which provides a high-level evidence for the effectiveness assessment of heat-sensitive moxibustion in community management. Focusing on the key links of randomization, e.g. block randomization, stratified randomization, cluster randomization, sample size allocation, allocation concealment and blinding, the paper elaborates the advantages, disadvantages and technical details of two-stage randomization with consideration of patient preference in pragmatic randomized controlled trials of heat-sensitive moxibustion in community. It facilitates improving the quality of evidence, reproducibility and methodological homogeneity among different trials.

[Effect of electroacupuncture preconditioning on expression of Gasdermin D, Caspase-1 and IL-1ß in rats with myocardial ischemia reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture(EA) preconditioning on expression of Caspase-1, Gasdermin D(GSDMD) and interleukin-1ß(IL-1ß) in myocardial tissue of myocardial ischemia reperfusion injury (MIRI) rats in order to explore its underlying mechanisms in resisting MIRI. METHODS: Forty male rats were randomly divided into 4 groups: normal control (normal), sham operation (sham), MIRI model and EA groups. The MIRI model was established by ligation of the left anterior descending branch of the left coronary artery for 30 min and perfusion. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once a day for 3 consecutive days. The echocardiography was used to analyze the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and left ventricular ejection fraction (LVEF, by using Teichholz formula) 4 h after modeling. The myocardial TTC staining was used to observe the proportion of the infarct area, and Western blot was used to detect the expression levels of GSDMD, Caspase-1, IL-1ß proteins in the myocardium. RESULTS: Compared with the normal group, the immunoactivity of GSDMD was increased in the sham group (P<0.05). Compared with the sham group, the LVEF was significantly decreased (P<0.000 1), while the myocardial infarction area, immunoactivity of GSDMD, and the expression levels of Caspase-1, GSDMD and IL-1ß proteins were considerably increased in the model group (P<0.000 1, P<0.001). In comparison with the model group, the decreased ejection fraction and the increased myocardial infarction area, and Caspase-1, GSDMD and IL-1ß expression were reversed in the EA group (P<0.001, P<0.000 1, P<0.01). CONCLUSION: EA preconditioning may ameliorate myocardial injury in MIRI rats which may be associated with its function in down-regulating the expression of myocardial Caspase-1 protein to reduce cardiomyocyte pyroptosis.

[Technical recommendations for pragmatic randomized controlled trials of heat-sensitive moxibustion in community (â ¡): organization, implementation and follow-up visits].

Based on the community research experience of heat-sensitive moxibustion, this study explained technical recommendations for pragmatic randomized controlled trials (pRCTs) of heat-sensitive moxibustion in community from 7 aspects: selection of community research sites, ethical approval and registration, patient recruitment, training of standard operating procedures, ensuring patient compliance, quality control of follow-up visits and patient safety, which aimed to reduce the difficulty of research execution and improve the quality of pRCTs implementation and follow-up visits of heat-sensitive moxibustion.

Remote Conditioning by Rhythmic Compression of Limbs Ameliorated Myocardial Infarction by Downregulation of Inflammation via A2 Adenosine Receptors.

Background: Remote ischemic conditioning (RIC) is a cardioprotective phenomenon, yet transient ischemia is not a requisite trigger for remote cardioprotection. In fact, RIC is a stimulus compound containing interruption of the blood vessel and tissue compression. In this study, we evaluate the effects of remote tissue compression on infarct size after myocardial infarction and explore its preliminary mechanisms. Methods and Results: We used a murine model of myocardial infarction to assess ischemia injury and identified remote conditioning by rhythmic compression on forelimb as a novel cardioprotective intervention. We show that the cardioprotective signal transduction of remote conditioning from the trigger limb to the heart involves the release of adenosine. Our results demonstrate that A2a and A2b receptors are indispensable parts for cardioprotection of remote conditioning, which is linked to its anti-inflammatory properties by the subsequent activation of cAMP/PKA/NF-κB axis. Conclusion: Our results establish a new connection between remote tissue compression and cardiovascular diseases, which enhances our cognition about the role of tissue compression on RIC cardioprotection.

[Effect of electroacupuncture pretreatment on transient receptor potential vanilloid 1(TRPV1)/calcitonin gene-related peptide(CGRP) signal and NF-κB p65 protein expression in rats with acute myocardial ischemia].

OBJECTIVE: To observe the effect of electroacupuncture(EA)pretreatment on transient receptor potential vanilloid 1(TRPV1)/calcitonin gene-related peptide(CGRP)signal and nuclear factor-κB p65 (NF-κB p65) protein expression in myocardial tissue of acute myocardial ischemic injury (AMI) rats, and to investigate the possible mechanism of electroacupuncture pretreatment against AMI. METHODS: A total of 60 adult male SD rats were randomly divided into blank control, sham operation, model and EA pretreatment groups, 15 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending (LAD)branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the sham operation group. In the EA pretreatment group, bilateral "Neiguan"(PC6) acupoints were selected, with intensity of 2 mA and frequency of 2 Hz/100 Hz, for 20 min, once daily for 7 days before modeling. Electrocardiogram (ECG) was recorded by physiological signal acquisition system, and the ST segment potential offset values of standard Ⅱ lead were analyzed before surgery，30 min and 24 h after operation. The TTC staining was used to observe the percentage of myocardial infarction area. The HE staining was used to observe the pathological changes of myocardial tissue and the degree of inflammatory cell infiltration. And Western blot was used to detect TRPV1/CGRP signal and NF-κB p65 protein expression levels in myocardial tissue. RESULTS: Compared with the sham operation group, the ECG-J point potential in the model group was significantly increased at 30 min and decreased at 24 h after operation (P<0.05), myocardial infarction area increased significantly (P<0.05), the myocardial fibers were obviously disordered, inflammatory cell infiltration was obvious, and the expressions of TRPV1，CGRP and NF-κB p65 proteins were all increased (P<0.05). Compared with the model group, the EA pretreatment group was decreased in the ECG-J point potential at 30 min after operation(P<0.05), significantly reduced in myocardial infarction area (P<0.05), improved in the morphology of myocardial fibers, reduced ininflammatory cell infiltration, and increased in the protein expressions of TRPV1 and CGRP in myocardium (P<0.05), significantly decreased in the protein expression of NF-κB p65 (P<0.05). CONCLUSION: EA pretreatment may enhance TRPV1/CGRP signaling, down-regulate NF-κB p65 protein expression, reduce myocardial inflammatory response status, improve AMI injury, and reduce myocardial infarction area.

[Effect of electroacupuncture at "Neiguan" (PC 6) on cardiac function and inflammatory factors of acupoint area in rats with acute myocardial ischemia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function and cardiomyocyte apoptosis in rats with acute myocardial ischemia (AMI), and to explore the correlation between myocardial protective effect of EA and inflammatory factors i.e. interleukin-1ß (IL-1ß) and interleukin-17 (IL-17) of "Neiguan" (PC 6) area. METHODS: A total of 40 male SD rats with normal ultrasonic cardiogram were randomized into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The AMI model was established by ligating the left anterior descending (LAD) branch of the coronary artery in the model group and the EA group, while the threading without ligating was adopted in the sham-operation group and the sham-operation plus EA group. In the sham-operation plus EA group and the EA group, EA at bilateral "Neiguan" (PC 6) was applied, with disperse-dense wave, 2 Hz/100 Hz in frequency and 2 mA in density, once a day, 20 min a time for 3 days. The cardiac ejection fraction (EF) and fractional shortening (FS) were measured by ultrasonic cardiogram to evaluate the cardiac function, the cardiomyocyte apoptosis was detected by TUNEL staining, the infiltration of inflammatory factors of "Neiguan" (PC 6) area was observed by H.E. staining, the expression of inflammatory factors IL-1ß and IL-17 of "Neiguan" (PC 6) area was detected by immunofluorescence staining. RESULTS: Compared with the sham-operation group, EF and FS were decreased (P<0.001), the average optical density of cardiomyocyte apoptosis was increased (P<0.001), the infiltration of inflammatory factors was obvious in skin dermis of "Neiguan" (PC 6) area in the model group; the positive expression of IL-1ß and IL-17 of "Neiguan" (PC 6) area was increased in the model group and the sham-operation plus EA group (P<0.001, P<0.01). Compared with the model group, EF and FS were increased (P<0.01), the average optical density of cardiomyocyte apoptosis was decreased (P<0.01), the infiltration of inflammatory factors was aggravating in skin dermis of "Neiguan" (PC 6) area, and the positive expression of IL-1ß and IL-17 of "Neiguan" (PC 6) area was increased in the EA group (P<0.001, P<0.01). CONCLUSION: Electroacupuncture at "Neiguan" (PC 6) can improve the cardiac function and reduce the apoptosis of cardiomyocyte in rats with acute myocardial ischemia, its mechanism may be related to the regulation of the inflammatory factors of "Neiguan" (PC 6) area.

[Effect of electroacupuncture on expression of IL-23/IL-17 axis and TLR4 in infarcted tissue in rats with myocardial infarction].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of interleukin (IL) -23/IL-17 axis and Toll-like receptor 4 (TLR4) in the infarcted tissue in rats with myocardial infarction (MI), and to explore the mechanism of EA on alleviating MI injury. METHODS: Forty male SD rats were randomly divided into a sham-operation group, a sham-operation plus EA group, a model group and an EA group, 10 rats in each group. The MI models were established by ligation of left anterior descending coronary artery in the model group and EA group, while only threading was performed in the sham-operation group and sham-operation plus EA group. The rats in the sham-operation plus EA group and EA group were treated with EA at "Neiguan" (PC 6), disperse-dense wave, 2 Hz/100 Hz, 2 mA, once a day, 20 min each time, for 3 days. After the intervention, the ejection fraction (EF) was measured by echocardiography to evaluate the cardiac function; the infarct area was measured by TTC staining; the HE staining was used to observe the morphological changes of myocardial tissue; the levels of IL-23 and IL-17 in infarcted tissue were detected by ELISA; the protein expression of TLR4 in infarcted tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the EF was decreased (P<0.01), the infarct area was increased (P<0.01), the myocardial fiber injury was obvious, accompanied by inflammatory cell infiltration, and the contents of IL-23, IL-17 and the expression of TLR4 in infarcted tissue were increased in the model group (P<0.01). Compared with the model group, the EF was increased (P<0.05), the infarct area was reduced (P<0.05), the myocardial fiber injury was significantly improved, the inflammatory cell infiltration was reduced, and the contents of IL-23, IL-17 and TLR4 expression in infarcted tissue were decreased in the EA group (P<0.05). CONCLUSION: EA may alleviate the excessive inflammatory response after MI by inhibiting the expression of IL-23/IL-17 axis in MI rats, and TLR4 may be involved during the process.

The safety and effectiveness of rehabilitation exercises on COVID-19 patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) is spreading fast starting late 2019. It mainly affects the human respiratory system. Many reports revealed that rehabilitation exercise can improve respiratory function and relieve the pressure from diseases, but there is no evidence to prove its effects on COVID-19. This protocol of systematic review and meta-analysis will clarify the safety and effectiveness of rehabilitation exercises on different COVID-19 patients. METHODS AND ANALYSIS: Related studies will be retrieved from Web of Science, Cochrane Library, PubMed, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, Wan fang Database, ClinicalTrials, WHO Trials, and Chinese Clinical Trial Registry. Pre-defined inclusion and exclusion criteria will be used by two researchers independently for extracting data from literatures. Clinical recovery time and effective rates will be assessed as the primary outcomes. Changes of patient's condition, pulmonary function, respiratory function and activity of daily living will be assessed as the secondary outcomes. Fixed effect model will be used for evaluating efficiency. Considering clinical heterogeneity, random effect model will be used for continuous outcomes. Funnel charts, subgroup analysis and sensitivity analysis will be used to explore sources of heterogeneity. Endnote X9.3 will be used to manage data screening. The statistical analysis will be completed by RevMan5.2 and Stata/SE 15.1 software. RESULT: This study will assess effects and safety for practicing rehabilitation exercises on COVID-19 patients. CONCLUSION: The conclusion of this study will provide evidence to prove the safety and effectiveness of rehabilitation exercises on COVID-19 patients.