Gefapixant, a Novel P2X3 Antagonist, Protects against Post Myocardial Infarction Cardiac Dysfunction and Remodeling Via Suppressing NLRP3 Inflammasome.

OBJECTIVE: The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is specifically expressed on nerves, especially on pre-ganglionic sensory fibers. This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction. METHODS: The Sprague-Dawley rats were divided randomly into three groups: sham group-myocardial infarction group, and myocardial infarction with gefapixant treatment group. Myocardial infarction was induced by left anterior descending branch ligation. The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin (HE) staining and myocardial injury biomarkers. Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III. The sympathetic innervation was detected by norepinephrine concentration (pg/mL), in-vivo electrophysiology, and typical sympathetic biomarkers. Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology, quantitative realtime PCR (qPCR) and Western blotting. RESULTS: It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio. Furthermore, gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS, and decreased LVIDd and LVIDs. The expression levels of collagen I and collagen III, and TNF-α were all decreased by P2X3 inhibition. Mechanistically, the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 (NLRP3) inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1ß (IL-1ß) and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation. CONCLUSION: It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance, cardiac dysfunction, and remodeling possibly via inactivating NLRP3 inflammasome.

Role of the system of orexin/receptors in neurological diseases / 生理学报

The neuropeptide orexin is widely distributed in the nervous system. Previous studies showed that orexin is involved in the feeding behavior regulation by binding to its receptor 1 (OX1R) and receptor 2 (OX2R) to activate the downstream signaling pathway. Recent studies have demonstrated that the system of orexin and its receptors are also involved in important physiological processes such as sleep-wake, learning and memory, and pathological processes of various neurological diseases. In this review, we summarized the research progress on the function of the orexin and its receptor system in physiological and pathological processes, and revealed the correlation between orexin and nervous system diseases, in order to provide the theoretical guidance for the diagnosis and treatment of the related diseases in the future.

Clonidine adhesive patch for the treatment of tic disorders: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of clonidine adhesive patch for tic disorders (TDs). METHODS: Medline, Embase, Cochrane central register of controlled trials and Chinese databases of CBM, CNKI were searched from inception to 08.2016 for randomized controlled studies (RCTs), open-label control studies of clonidine adhesive patch versus other medications or/and placebo for TDs. The cochrane Handbook for Systematic Reviews of Interventions was used to guide our study. RESULTS: Six studies involving 1145 participants were included in this study. Among these studies, two study (N = 513 patients) used placebo as a control and four studies (N = 632 patients) used positive drug controls. The results of meta-analysis suggested that clonidine adhesive patch may be as effective as haloperidol or tiapride for TDs. Adverse events (AEs) were reported in all studies, and the most common AEs of clonidine adhesive patch were rash (8.9%), lightheadedness (8.0%), dry mouth (4.0%). The AEs of clonidine adhesive patch were slight. CONCLUSION: These data provide moderate quality evidence that clonidine adhesive patch might be an effective and safe treatment option for TDs, and results from further trials are urgently needed to extend the evidence base.

The efficacy and safety of aripiprazole for tic disorders in children and adolescents: A systematic review and meta-analysis.

The aims are to evaluate the efficacy and safety of aripiprazole for tic disorders (TDs) in children and adolescents. We searched PubMed, Embase, PsychINFO, Cochrane database as well as Chinese databases of CNKI, VIP, CBM and Wanfang from the database inception to October 2016, and 17 full-text studies (N=1305) were included in our article. The meta-analysis of 10 studies (N=817) showed that there was no significant difference in the reduction of total YGTSS score between aripiprazole and other drugs, and meta-analysis of 7 studies (n=324) which used tic symptom control ≧30% as outcome measure showed that there was no significant difference between aripiprazole and other treatments. The most common AEs of aripiprazole were the drowsiness, nausea/vomiting and increased appetite, and meta analysis which used the TESS scale as the outcome measurement showed that there was a significant difference between aripiprazole and haloperidol. In conclusion, these data provide moderate quality evidence that aripiprazole could be an effective and safe treatment option for TDs, and results from further trials are urgently needed to extend this evidence base.

Effects of comprehensive care on living conditions of hemophiliac patients / 中华护理杂志

Objective To analyze the impact of comprehensive care on living conditions of hemophiliac patients in China.Methods Based on the managerial experience of the World Federation of Hemophilia(WFH) and China's national condition,we carried out comprehensive care on patients with hemophilia (PWH) in our center.Questionnaire surveys on living condition were conducted before and after intervention (in 2004 and 2016,respectively) to Beijing's permanent hemophiliacs.The results of questionnaires conducted in 2004 were settled as baseline data,and a comparative analysis was done between the baseline data and the results of surveys conducted in 2016 in the PWH who had received comprehensive care for at least 2 years.Results Totally 109 cases received baseline survey whereas 136 cases received questionnaires after intervention.Thirty-nine(28.7％) and 70(51.5％) patients conducted prophy-laxis or home treatment after receiving comprehensive care,respectively.There was significant difference (P＜0.01)in terms of treatment timeliness.Similar results were found (P＜0.01)in terms of times of bleeding per year,and there was significant improvement (P＜0.01) on joint disorder after comprehensive care.Conclusion After receiving comprehensive care,PWH are more willing to accept and conduct prophylaxis and home treatment.The bleeding can be controlled more effectively,and the treatment can be given more timely.Meanwhile,PWH can receive more improvements in joint and walking function.

Effects of comprehensive care on living conditions of hemophiliac patients / 中华护理杂志

Objective To analyze the impact of comprehensive care on living conditions of hemophiliac patients in China.Methods Based on the managerial experience of the World Federation of Hemophilia(WFH) and China's national condition,we carried out comprehensive care on patients with hemophilia (PWH) in our center.Questionnaire surveys on living condition were conducted before and after intervention (in 2004 and 2016,respectively) to Beijing's permanent hemophiliacs.The results of questionnaires conducted in 2004 were settled as baseline data,and a comparative analysis was done between the baseline data and the results of surveys conducted in 2016 in the PWH who had received comprehensive care for at least 2 years.Results Totally 109 cases received baseline survey whereas 136 cases received questionnaires after intervention.Thirty-nine(28.7％) and 70(51.5％) patients conducted prophy-laxis or home treatment after receiving comprehensive care,respectively.There was significant difference (P＜0.01)in terms of treatment timeliness.Similar results were found (P＜0.01)in terms of times of bleeding per year,and there was significant improvement (P＜0.01) on joint disorder after comprehensive care.Conclusion After receiving comprehensive care,PWH are more willing to accept and conduct prophylaxis and home treatment.The bleeding can be controlled more effectively,and the treatment can be given more timely.Meanwhile,PWH can receive more improvements in joint and walking function.

Association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population.</p><p><b>METHODS</b>XbaI and EcoRI polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia).</p><p><b>RESULTS</b>The difference in the genotypic distributions could be neglected across the groups. The prevalence of X+ allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X+ allele between cases (5.7%) and controls (P = 0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P = 0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E+ was most frequent and no haplotype could significantly contribute to essential hypertension.</p><p><b>CONCLUSION</b>The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.</p>

Linkage analysis of chromosome 14 and essential hypertension in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypertension is a complex biological trait that influenced by multiple factors. The encouraging results for hypertension research showed that the linkage analysis can be used to replicate other studies and discover new genetic risk factors. Previous studies linked human chromosome 14 to essential hypertension or blood pressure traits. With a Chinese population, we tried to replicate these findings.</p><p><b>METHODS</b>A linkage scan was performed on chromosome 14 with 14-microsatellite markers with a density of about 10 centi Morgen (cM) in 147 Chinese hypertensive nuclear families. Multipoint non-parametric linkage analysis and exclusion mapping were performed with the GENEHUNTER software, whereas quantitative analysis was performed with the variance component method integrated in the SOLAR package.</p><p><b>RESULTS</b>In the qualitative analysis, the highest non-parametric linkage score is 1.0 (P = 0.14) at D14S261 in the single point analysis, and no loci achieved non-parametric linkage score more than 1.0 in the multipoint analysis. Maximum-likelihood mapping showed no significant results, either. Subsequently the traditional exclusion criteria of the log-of-the-odds score-2 were adopted, and the chromosome 14 with lambda s > or = 2.4 was excluded. In the quantitative analysis of blood pressure with the SOLAR software, two-point analysis and multipoint analysis suggested no evidence for linkage occurred on chromosome 14 for systolic and diastolic blood pressure.</p><p><b>CONCLUSION</b>There was no substantial evidence to support the linkage of chromosome 14 and essential hypertension or blood pressure trait in Chinese hypertensive subjects in this study.</p>