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Abstract:The purpose of this study was to determine the cardioprotective effects of the repetitive pretreatment of acupuncture in rats with myocardial ischemia and reperfusion (MIR). Experimental MIR was produced by ligating and reperfusing the left anterior descending coronary artery in the rats. The elevated ST segments of electrocardiogram (ECG), cardiac arrhythmias, and ratio of infarct size/risk zone were compared among the normal control (NC), ischemia and reperfusion (IR), electro-acupuncture (EA), electro-acupuncture plus propranolol (EAP), and EA at nonacupoint (EAN) groups. Before the experiment, EA was applied at bilateral Neiguan acupoints (PC6) in the forelimbs in EA and EAP groups for 30 min once a day for 3 consecutive days. In the EAN group, the same EA treatment was administered at bilateral nonacupoints in the hind limbs. In the EAP group, propranolol, a nonspecific antagonist of β-adrenoceptors, was administered intraperitoneally 15 min before each EA pretreatment. The results showed that the elevated ST segment of ECG, cardiac arrhythmia score, and ratio of infarct size/risk zone were significantly attenuated in the EA group when compared with those in the IR group (P < 0.05), indicating a cardioprotection of EA pretreatment. When propranolol was given before each EA pretreatment in the EAP group, the cardioprotective effect of EA pretreatment was abolished, showing an involvement of β-adrenoceptors in mediating the effect of EA pretreatment. There was no significant cardioprotective effect observed in the EAN group. The results suggest that pretreatment may be a better way to apply acupuncture in the prevention and treatment of coronary heart disease.

Our previous study showed that electro-acupuncture (EA) pretreatment protects the heart from injury of ischemia. The present study explored further whether adenylate cyclase (AC), protein kinase A (PKA), and L-type Ca 2+ channel, the β 1 -AR signaling components modulating intracellular Ca 2+ ([Ca 2+ ] i ), are involved in the mediation of the antiarrhythmic effect of EA pretreatment in the rats from which the hearts were subsequently isolated and subjected to simulative global ischemia and reperfusion (SGIR). SGIR was performed by perfusing the isolated heart at a low flow followed by normal perfusion. Adult rats were randomized into four groups, namely, normal control (NC), SGIR, EA, and NC plus EA (NCEA) groups. The rats in the EA and NCEA groups were given EA pretreatment at bilateral Neiguan points (PC6) for 30 min once a day in 3 consecutive days before the hearts were isolated and perfused. The arrhythmia score and the response of [Ca 2+ ] i to the activators of AC, PKA, and L-type Ca 2+ channel in single ventricular myocyte isolated from the hearts subjected to SGIR were compared among the groups. The results showed that the arrhythmia score was significantly higher in the SGIR group as compared with the NC and NCEA groups. The SGIR-enhanced arrhythmia score was significantly attenuated in the EA group. More interesting, EA pretreatment also attenuated the SGIRenhanced response of [Ca 2+ ] i to the activators of AC, PKA, and the L-type Ca 2+ channel in the myocytes isolated from the hearts subjected to SGIR. In conclusion, EA pretreatment can produce an antiarrhythmic effect in the rat of SGIR. AC, PKA and the L-type Ca 2+ channel are involved in the mediation of the antiarrhythmic effect of EA pretreatment.

IntroductionPsoriasis is a life-long, immune-mediated disease that greatly reduces the quality of life of patients. Plaque psoriasis is the most common form of psoriasis. Treatment options for plaque psoriasis with good tolerance and sufficient response remain profoundly limited. Based on mechanistic findings that suggest the key pathogenic role of interleukin (IL)-17 in plaque psoriasis, we hypothesise that GR1501, a new monoclonal antibody (IL-17A targeted), will be an efficacious treatment for plaque psoriasis. This phase I/II trial aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of GR1501.Methods and analysisA multicentre, randomised, double-blind, phase I/II dose escalation and expansion trial will be conducted at four hospitals in China. In total, 226 patients with plaque psoriasis will be enrolled in the study, with 46 cases in the dose-escalation stage and 180 cases randomised to GR1501 or the placebo in a 3:1 ratio in the expansion cohort. The primary outcomes are safety and tolerability; the secondary outcomes include pharmacokinetics, immunogenicity and efficacy.Ethics and disseminationThe study is in accordance with the Declaration of Helsinki, and the ethics approvals of the protocol have been obtained from the ethics committees of all participating centres, including Peking University People’s Hospital, Chinese PLA General Hospital, The First Affiliated Hospital, College of Medicine, Zhejiang University and the Second Xiangya Hospital of Central South University. The findings of the study will be presented in published journals or at scientific conferences or meetings.Trial registration numberChiCTR1800017956.

We aimed to evaluate the effects of mecobalamin on the cerebral ischemia-reperfusion injury of spontaneously hypertensive stroke prone rats. 72 male rats were randomly divided into control group, model group, nimodipine group, high-dose mecobalamin group, middle-dose mecobalamin group and low-dose mecobalamin group (n=12). All groups were administrated intragastrically every morning once a day for 7 continuous days. The model of 2 h of focal cerebral ischemia and 24 h of reperfusion was established by blocking middle cerebral artery. Neurological deficits were graded with reference to the Longa method. Cerebral edema was determined using the wet-dry weighing method. The volume of cerebral infarction was measured by triphenyltetrazolium chloride staining and the levels of tumour necrosis factor alpha, interleukin-1 beta and interleukin-8 were measured by radioimmunoassay. High and middle-dose mecobalamin significantly reduced the volume of cerebral infarction, alleviated cerebral edema and improved nerve function compared with those of the model group (p<0.05). Compared with the model group, high and middle-dose mecobalamin significantly reduced the levels of tumour necrosis factor alpha, interleukin-1 beta and interleukin-8 in cerebral tissue (p<0.05). Mecobalamin protected spontaneously hypertensive stroke prone rats from cerebral ischemia-reperfusion injury, which may be related to the decreased levels of tumour necrosis factor alpha, interleukin-1 beta and interleukin-8 in cerebral tissue.