从“阳化气,阴成形”角度阐释肠促胰素在糖脂代谢中的作用

糖脂代谢是人体生命活动中重要的物质代谢过程,其合成代谢与分解代谢的相互协调确保正常的生理功能。阴阳学说中“阳化气”“阴成形”的理论是对机体生命规律及物质与能量关系的生动描述。抑胃肽(GIP)和胰高血糖素样肽1(GLP-1)作为2种主要的肠促胰素,由肠道内分泌细胞产生,作用于胰腺、脑、肝脏等组织,合成与分解饮食中的糖类与脂质,为机体提供能量并存储能量。其中,GIP刺激白色脂肪,促进脂质储存,具有类似于“阴成形”的作用,GLP-1刺激棕色脂肪,增加产热,具有类似于“阳化气”的作用,二者之间还有对立制约、互根互用、消长平衡的阴阳关系。GIP与GLP-1的关系与机体糖脂代谢的生理、病理学密切相关。糖脂代谢紊乱早期均以瘀滞状态为主,糖尿病以阳盛阴病为主,而肥胖症以阴盛阳病为主。调整阴阳可改善糖脂代谢紊乱状态,现代医学研究表明,共同激动GIP与GLP-1,会产生更好地控制血糖、体质量的效果。本文借助中医阴阳理论,以肠促胰素为切入点,浅析GIP与GLP-1在糖脂代谢中的作用关系,以丰富中医药对糖尿病、肥胖症等代谢疾病的研究思路。     

Targeted Mutations in the Fusion Peptide Region of La Crosse Virus Attenuate Neuroinvasion and Confer Protection against Encephalitis

La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.     

Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation

BackgroundCalcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre.MethodsThis was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up.ResultsOne hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p < 0.0001) and severe (15 to 5, 67% reduction, p < 0.0001) headache days. 39.8% of patients achieved at least a 30% reduction in total headache days; 61.8% of patients achieved at least a 50% reduction in severe headache days. Meeting either of these thresholds was considered a positive response, 68% of patients achieved this. Presence of daily headache pattern was negatively associated with response, (56% response vs. 90% without daily headache, p = 0.0003). There was no association between age, gender, presence of medication overuse or number of previously tried prophylactic treatments and response to erenumab. 43% of patients reported at least one adverse effect, most commonly constipation (26%); treatment was discontinued in 3 patients due to adverse effects.ConclusionsErenumab was an effective treatment for chronic migraine in this treatment resistant population over 3 months of follow up. Presence of daily headache predicted poorer response but there was still a significant positive response rate in this group.     

乌司他丁干预对急性脑梗死患者血清D－二聚体、脑钠肽水平及认知功能的影响

目的：探讨乌司他丁干预对急性脑梗死患者血清D－二聚体、脑钠肽（brain natriuretic peptide,BNP）水平及认知功能的影响。方法：选取2012年1月—2013年1月急性脑梗死患者98例作为观察组,另选取30例健康自愿者作为对照组。观察组患者在基础治疗的基础上给予乌司他丁10万U静脉滴注,每8h给药1次,连续治疗7d。检测对照组人群和观察组患者治疗前和治疗1、3、5、7d时血清D－二聚体、BNP水平,并采用蒙特利尔认知评估量表对2组人群进行认知功能评价。结果：治疗前,观察组患者血清D－二聚体、BNP水平均明显高于对照组（P＜0．01）。观察组患者治疗3、5、7 d时血清D－二聚体、BNP水平均明显低于治疗前（P＜0．05）,并于治疗1 d时达到最高值[分别为（3．27±0．46）mg／L、（161．78±45．98）ng／ml],治疗7 d时达到最低值[分别为（1．67±0．76）mg／L、（109．67±31．78）ng／ml];观察组患者认知功能障碍发生率为28％（28．57％,28／98）。结论：乌司他丁干预可有效降低急性脑梗死患者血清D－二聚体、BNP水平,并可预防认知功能障碍的发生,是急性脑梗死的有效辅助治疗方法,值得临床推广。     

固相法合成心肌兴奋肽及其类似物

用Boc-和Tos-基团分别保护氨基和侧链胍基,以1%交联度聚苯乙烯二苯甲氨基树脂为载体,用DCC固相法合成肽,HF断裂肽树脂键和去除侧链保护基团,粗产物经高效液相层析纯化,合成了心肌兴奋肽Phe-Met-Arg-Phe-NH_2及其类似物Phe-Pro-Arg-Phe-NH_2,并观察了此二种肽对大鼠血压和心率的影响。     

不同剂量氟伐他汀对慢性心力衰竭大鼠心肌组织血管紧张素Ⅱ和脑利钠肽水平影响的实验研究

目的 探讨不同剂量氟伐他汀对阿霉素诱导的慢性心力衰竭大鼠心肌组织血管紧张素Ⅱ(AngⅡ)和脑利钠肽(BNP)水平的影响. 方法将60只SD大鼠随机分为正常对照组、心力衰竭对照组、小剂量氟伐他汀组和大剂量氟伐他汀组,除正常对照组予0.9%氯化钠注射液腹腔注射外,余3组均采用阿霉素腹腔注射的方法建立慢性心力衰竭大鼠模型.模...     

腹安汤治疗腹泻型肠易激综合征40例疗效观察及机制探讨

目的:探讨腹安汤治疗腹泻型肠易激综合征的临床疗效及对血浆血管活性肠肽(VIP)、P物质(SP)的影响。方法:将80例患者随机分为治疗组和对照组,每组40例,治疗组用腹安汤,对照组用匹维溴胺,对比两组的临床疗效和治疗前后血浆VIP、SP水平。另选20例体检健康者作正常对照。结果:治疗组总有效率92.5%,对照组总有效率77.5%,两组总有效率比较,差异有统计学意义(P<0.05);血浆VIP、SP水平在治疗组用药前后比较,有显著性差异(P<0.05),在治疗组用药后与对照组比较,有显著性差异(P<0.05)。结论:腹安汤治疗腹泻型肠易激综合征疗效明显,值得临床推广应用。其作用机制之一可能是通过调节血浆中VIP、SP的分泌而达到治疗效果。     

脑钠肽和胱抑素C在糖尿病肾病早期诊断中的临床价值

目的：探讨脑钠肽（B-type natriuretic peptide,BNP）和胱抑素C（Cystatin C,CysC）在糖尿病肾病早期诊断中的临床意义。方法：采用放射免疫分析技术对72名糖尿病肾病（diabetic ne-phropathy,DN）患者血BNP和CysC以及尿微量白蛋白排泄率（urine albumin excretion rate,UAER）分别进行测定。结果：大量蛋白尿组（UAER≥300mg/d）、微量蛋白尿组（30mg/d≤UAER〈300mg/d）和极微量蛋白尿组（UAER〈30mg/d）3组DN患者BNP和CysC浓度比较,差异具有统计学意义（P〈0.05-0.01）,且BNP和CysC与尿微量白蛋白排泄率呈显著正相关（r=0.519,P〈0.01和r=0.773,P〈0.01）。结论：BNP和CysC联合测定对糖尿病肾病的早期诊断具有良好的临床价值。     

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease

Background The mitochondrial displacement loop （D-loop） accumulates mutations and single nucleotide polymorphisms （SNPs） at a higher frequency than other regions of mitochondrial DNA （mtDNA）.We previously identified disease riskassociated SNPs in the D-loop of chronic kidney disease （CKD） patients; in this study,we investigated the association of age-at-onset and D-loop SNPs in CKD patients.Methods The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008.The age-at-onset curve of the CKD patients was calculated using the KaplanMeier method at each SNP site,and compared using the log-rank test.Results The mean age of 119 CKD patients was （55.6±14.2） years,and 56.3% were males.The mean estimated glomerular filtration rate （eGFR） was （81.2±12.4） ml·min^-1·1.73 m^-2,with 79.8% （n=95） of patients having an eGFR 〈60 ml·min^-1·1.73 m^-2.All participants had an eGFR 〉30 ml·min^-1·1.73 m^-2.The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients.The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test.The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site （P=0.010）.Conclusions Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients.Accordingly,the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.     

急性肺栓塞患者BNP、CTnI、D-dimer水平改变及其临床意义

【目的】探讨检测急性肺栓塞患者的血浆脑钠肽（BNP）、肌钙蛋白I（cTnI）及D‐二聚体（D‐dimer）水平变化的临床意义。【方法】选择本院2009年1月至2013年12月收治的急性肺栓塞患者64例,根据患者病情分为大面积肺栓塞组（ n ＝27）和非大面积肺栓塞组（ n ＝37）,对两组患者血浆cTnI、BNP及D‐dimer水平进行测定,观察比较两组患者各指标水平的变化及右心功能和病死率。【结果】大面积肺栓塞组BN P、血浆cTnI水平明显高于非大面积肺栓塞组,两组比较差异有显著性（ P ＜0．05）;两组D‐dimer浓度比较差异无统计学意义（ P ＞0．05）;大面积肺栓塞组的右心功能不全者和病死率均高于非大面积肺栓塞组,两组比较差异有统计学意义（ P ＜0．05）。【结论】检测BNP、cTnI及D‐dimer水平对APE患者临床诊断、临床决策及预后判断具有重要的临床意义。