Molecular mechanism of miR-382 in the pathogenesis of renal tubulointerstitial fibrosis

Objective To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF). Methods Human kidney epithelial cells (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity, as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1), which was further verified by 3′-untranslated region luciferase assay and site-directed mutagenesis. The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model. Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO, and repeated the dosage 24 h after the surgery. For clinical verification, renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected, 6 patients with moderate to severe TIF and 6 patients without TIF. The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry. Results HSPD1 was confirmed to be a new, direct target gene of miR-382 by in vitro 3′-untranslated region luciferase assay and site-directed mutagenesis. The development of epithelial transition in HK2 cells was accompanied with up-regulation of miR-382 [(6.54±0.96) vs (1.12±0.26), P＜0.05]. Blocking the expression of miR-382 could reversed the progression of epithelial transition partially. In UUO mice the abundance of miR-382 was up-regulated [(6.89±2.47) vs (1.00±0.42), P＜0.01] while HSPD1 and Trx were down-regulated compared with the sham group. Down-regulation of miR-382 was associated with significant decrease in TIF, but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1: (0.34±0.10) vs (0.14±0.05); Trx: (0.79±0.18) vs (0.36±0.16); all P＜0.05]. The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF. Conclusions miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice. HSPD1 is one of the target genes of miR-382. The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis.     

Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease Activity

Background:Vitiligo is a progressive depigmenting disorder characterized by the loss of functional melanocytes from the epidermis. The etiopathogenesis of vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to connect stress to the skin. HSPs were found to be implicated in autoimmune diseases such as rheumatoid arthritis and other skin disorders as psoriasis.Results:Our analysis revealed a significantly higher expression of HSP-70 mRNA in lesional skin biopsies from vitiligo patients compared to nonlesional skin biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated with age, sex, or disease duration. The expression of HSP-70 was correlated with the disease activity and patients with active vitiligo showed higher mean HSP-70 level compared to those with inactive disease.Conclusions:HSP-70 plays a role in the pathogenesis of vitiligo and may enhance the immune response in active disease.     

Variations in the TRPV1 gene are associated to exertional heat stroke

ObjectivesExertional Heat Stroke (EHS) is one of the top three causes of sudden death in athletes. Extrinsic and intrinsic risk factors have been identified but the genetic causes still remain unclear. Our aim was to identify genes responsible for EHS, which is a necessary step to identify patients at risk and prevent crises.DesignGenetic and functional laboratory studiesMethodsWhole Exome Sequencing (WES) was performed to search for candidate genes in a cohort of 15 soldiers who had a documented EHS episode. In silico and in vitro functional studies were performed to evaluate the effect of mutations identified in the candidate gene TRPV1.ResultsWES led to the identification of two missense variations in the TRPV1 gene. These variations were very rare or unreported in control databases and located in critical domains of the protein. In vitro functional studies revealed that both variations induce a strong modification of the channel response to one of its natural agonist, the capsaicin.ConclusionsWe evidenced mutations altering channel properties of the TRPV1 gene and demonstrated that TRPV1, which is involved in thermoregulation and nociception, is a new candidate gene for EHS. Our data provide the bases to explore genetic causes and molecular mechanisms governing the pathophysiology of EHS.     

热敏灸小镇建设助力江西热敏灸产业发展的对策研究

近年来,江西资溪、丰城等地的实践探索表明,热敏灸小镇建设对于助推江西热敏灸产业发展具有十分重要的作用。然而,当前江西热敏灸小镇建设在标准、人才、组织、产品、服务等方面还存在诸多问题。为此,有必要在借鉴省外成功经验的基础上,从找准定位、培养人才、规范管理、健全标准、强化保障等五个方面进一步加强热敏灸小镇建设,助力江西热敏灸产业发展。     

疏肝和中汤联合雷贝拉唑治疗肝胃郁热型反流性食管炎临床研究

的:探讨疏肝和中汤联合雷贝拉唑治疗肝胃郁热型反流性食管炎患者的疗效。方法:选择68 例肝胃郁热型反流性食管炎患者,随机分为治疗组和对照组,每组34例。对照组给予雷贝拉唑治疗; 治疗组给予疏肝和中汤联合雷贝拉唑治疗,8周为1个疗程,随后观察患者治疗前后的症状积分变化及食管黏膜修复作用,及其对胃蛋白酶原I(PGI)、胃蛋白酶原比值(PGR)、胃泌素17(G-17)水平影响,评价两组药物的临床疗效。结果: 治疗组临床疗效总有效率91.2%; 对照组临床疗效总有效率70.1%,经统计学分析具有统计学意义,治疗组疗效优于对照组(P<0.05)。 中药对改善嘈杂易饥、神疲乏力、抑郁或心烦易怒、口苦咽干、大便秘结等肝胃郁热症状效果优于对照组。 中药组能更好促进食管黏膜修复作用,达到良好效果。 疏肝和中汤联合雷贝拉唑可以降低胃蛋白酶原I(PGI)、胃蛋白酶原比值(PGR)、胃泌素17(G-17)水平。结论:疏肝和中汤联合雷贝拉唑对反流性食管炎肝胃郁热证具有较好的临床疗效。     

Booster vaccination with a fractional dose of an oral cholera vaccine induces comparable vaccine-specific antibody avidity as a full dose: A randomised clinical trial

Antibody avidity is an important measure of the quality of vaccine-induced immune responses. Murine and human studies suggest that antibody avidity may be augmented by limiting access to antigen. The primary objective of this study was to evaluate in primed Swedish adults if booster vaccination with fractional doses (1/5th and 1/25th) of a model oral vaccine, the cholera vaccine Dukoral®, results in higher avidity antibody responses compared to boosting with a full vaccine dose. We also evaluated if fractional booster vaccination elicited similar magnitudes of antibody response compared to a full dose, and if the previously observed increase in antibody avidity after booster vaccination 1–2 years later occurred when boosting after a shorter interval.To this end, a randomised, open-label, exploratory Phase-II trial was performed. Swedish adults (n = 44), primed with two full doses of Dukoral®, were randomised into three groups and given a booster dose at either full (n = 14), 1/5th (n = 17) or 1/25th (n = 13) dose four months later. Antibody responses to cholera toxin B-subunit (CTB) were measured in serum and mucosal antibody in lymphocyte secretions (ALS).We found that the 1/5th and 1/25th booster doses had similar abilities as the full dose to induce significantly higher avidity anti-CTB antibody responses in both ALS and serum samples, as compared to after priming vaccination. There was a non-significant trend to lower magnitudes of ALS and serum IgA responses after the 1/5th compared to the full booster dose, and responses after the 1/25th dose were significantly lower.Our findings suggest fractional booster doses of Dukoral® four months after priming result in anti-toxoid mucosal antibody responses with increased antibody avidity compared to after priming vaccinations.ISRCTN registry identifier 11806026.     

Treatment of sialorrhoea with repeated ultrasound-guided injections of botulinum toxin A into the parotid and submandibular glands

Botulinum toxin injections are useful in patients with refractory sialorrhoea although the optimum treatment protocol and its efficacy over a long period of follow up are controversial. The aim of our prospective study was to examine the efficacy and complications of a protocol of repeated ultrasound-guided botulinum toxin injections of fixed doses at a tertiary children’s hospital. A total of 79 procedures were done in 34 patients who were followed up for two years. The overall complication rate was 3%. The outcome measures considered included the Drooling Frequency Severity Scale (DFSS), visual analogue scale (VAS), and carers’ assessments of the reduction in drooling. Our study highlighted two types on non-responders (primary and secondary) of which 3/34 required definitive surgical management. In summary, this study shows that a protocol of repeated injections of fixed doses of botulinum toxin A, while not beneficial in all cases, is a potentially valuable option for the safe and effective treatment of sialorrhoea in children.     

泻肾法在治疗小儿支气管哮喘中的运用观察

目的探讨泻肾法治疗小儿支气管哮喘的临床应用。方法选择我院自2010年1月—2011年12月小儿科收治的128例支气管哮喘的患儿,通过大量的文献,结合现代疾病本身的特点,所有患儿均经过中医辨证的肾实证病例,按照患儿入院登记的时间先后顺序,将患儿分为观察组（64例）与对照组（64例）,观察组给予大泻肾汤（黄芩、茯苓、细辛、干姜、芍药及甘草）,2 d/次,连续服用7 d。对照组服用氨茶碱,在临证中根据患儿的临床症状酌情使用抗生素,连续服用7 d,观察两组的治疗效果、症状消失时间,随访观察症状有无复发情况。结果观察组与对照组的疾病临床有效率分别为89.06%（57/64）、81.25%（52/64）,在中医证候疗效方面比较92.19%（59/64）、79.69%（51/64）,观察组的显效率明显优于对照组（P〈0.05）。结论小儿支气管哮喘患者主要按照肾实证加以辨治,通过服用泻肾清热方剂治疗,取得了一定的临床治疗效果。     

Treatment of headache with botulinum toxin administration

Botulinum toxin has been increasingly applied to the treatment of a wide variety of neurological disorders. Its application to headache disorders, and specifically those classified as migraine or tension-type, followed the observation of its effectiveness in decreasing pain. Studies that have primarily used botulinum toxin type A, but with varying dose regimens and sites of administration, have since observed its beneficial effects and in those subjects, headaches have lessened in their frequency or severity. However, questions that have primarily concerned dose and sites of administration have since arisen and clear guidelines for botulinum toxin use in headache disorders have yet to be developed.