吴茱萸次碱治疗重症急性胰腺炎的实验研究

目的：探讨吴茱萸次碱对大鼠重症急性胰腺炎（SAP）的疗效及其机制。 方法：50只SD大鼠随机均分为假手术组和4个实验组,实验组大鼠以5%牛磺胆酸钠胰胆管逆行注射制作SAP模型后,分别给予生理盐水、乌司他丁、吴茱萸次碱、乌司他丁+吴茱萸次碱处理。术后24 h,行病理学检查,并检测各组血清淀粉酶活性及血浆与胰腺组织和内皮素1（EF-1）、降钙素基因相关肽（CGRP）水平。 结果：除假手术组外,各实验组大鼠均胰腺组织均出现不同程度的胰腺炎病理改变;与假手术组比较,各实验组均出现不同程度的血清淀粉酶活性升高,血浆与胰腺组织ET-1浓度增加,而血浆与胰腺组织CGRP含量在吴茱萸次碱处理组与联合用药组均明显升高（均P<0.05）,其余实验组无明显改变（均P>0.05）;实验组中,各药物处理组胰腺病变程度、血清淀粉酶活性、血浆与胰腺组织ET-1浓度均较生理盐水处理的模型组明显降低,且均以联合用药组最为明显（均P<0.05）。 结论：吴茱萸次碱对大鼠SAP具有治疗作用,其作用可能与增加CGRP水平从而改善胰腺组织微循环有关。     

降钙素原对儿童急性阑尾炎严重程度的预测价值

目的 评价降钙素原（PCT）对儿童急性阑尾炎严重程度的预测价值.方法 收集2011年10月至2012年3月我们收治的93例诊断为急性阑尾炎的患儿临床资料,包括年龄、性别、入院时PCT及CRP、并发症（腹腔脓肿、肠梗阻）、住院时间等.根据手术所见或病理检查结果将患儿分为急性阑尾炎组和急性阑尾炎伴局限性或弥漫性腹膜炎组.结果 急性阑尾炎组53例,腹膜炎组40例.腹膜炎组出现并发症的比例高于急性阑尾炎组,住院时间较长,且PCT、CRP水平显著高于急性阑尾炎组（PCT：0.43 vs 3.37 ng/mL,P＜0.001,CRP：3.0vs13.8 mg/L,P＜0.001）.在诊断腹膜炎的敏感性、特异性、阳性预测值、阴性预测值方面,当PCT以0.93 ng/mL为阈值时,分别为85.0％、91.6％、88.3％、89.0％,而CRP以4.05 mg/L为阈值时,分别为90.0％、67.9％、67.9％、90.0％.结论 入院时PCT及CRP对儿童急性阑尾炎的严重程度具有一定的预测价值,且PCT性能略优于CRP.     

感觉神经肽在变应性鼻炎发病机制中的作用

目的通过对鼻腔蝶腭神经或交感神经切断后的动物进行致敏,观察其症状和鼻腔感觉神经肽的变化,探讨感觉神经肽在变应性鼻炎发病机制和疾病发展中的作用。方法①观察致敏兔鼻黏膜中P物质(substanceP,SP)和降钙素基因相关肽(calcitoningene-relatedpeptide,CGRP)4周内含量变化;②将20只兔分成三组,C组(蝶腭神经切除组,8只),D组(交感神经切除组,8只),E组(无手术干预组,4只)。C、D组术后致敏,2周及4周后各处死4只,取出鼻黏膜,行免疫组化检查。结果①A组致敏兔1～4周内SP和CGRP含量无明显变化;②C组致敏后两周与四周鼻黏膜中SP含量(16.1±0.77,15.02±0.24),E组致敏后2周与4周鼻黏膜中SP含量(20.68±0.01,20.56±1.27)。C组致敏后2周与4周,SP含量较E组明显低(P<0.01),C组致敏后2周和4周SP无明显差异(t=0.37,P>0.05)。D组致敏后2周与4周鼻黏膜中SP含量(34.13±1.45,33.23±1.99);D组致敏后两周和四周SP无明显差异(t=0.16,P>0.05),但较E组都明显增高(P<0.01)。CGRP的含量变化与SP有一致性。结论SP和CGRP与变应性鼻炎发病和发展有相关性。     

Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

BackgroundMonoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.MethodsThis observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO).ResultsWe enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01).ConclusionMigraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.     

大鼠下颌下腺降钙素的定位研究

目的观察大鼠下颌下腺降钙素（CT）的分布。方法取16只健康的SD大鼠下颌下腺,采用免疫组织化学SP法进行染色。结果在大鼠下颌下腺,可见CT反应阳性物,它们主要分布于浆液性腺泡、混合性腺泡的浆液细胞内,各级导管的上皮细胞也呈CT反应阳性。结论下颌下腺可能具有分泌降钙素的功能,提示下颌下腺可能参与钙磷代谢的生理调节。     

慢性心力衰竭时心肌组织中CGRP的含量变化及mRNA表达

目的探讨心肌组织降钙素基因相关肽(CGRP)含量变化及mRNA的表达与慢性心力衰竭(CHF)发生、发展的关系。方法以阿霉素(ADR)制备慢性心衰模型,采用放射免疫学方法和逆转录聚合酶链反应进行检测。结果CHF时,心肌组织中CGRP含量为34.82±3.01,高于正常心肌组织中CGRP的含量24.77±3.84,差异具有统计学意义;而CGRP的mRNA表达降低。结论心肌组织中CGRP含量变化及其mRNA的表达调控,与CHF的发生、发展密切相关。     

依达拉奉辅助亚低温对重型颅脑创伤的血清细胞因子及凝血功能的影响

目的探讨依达拉奉辅助亚低温治疗对重型颅脑创伤（TBI）患者的凝血功能及神经生长因子（NGF）、降钙素基因相关肽（CGRP）的影响。 方法选取沧州市中心医院神经外三科自2018年8月至2019年8月收治的62例重型TBI患者,按随机数字表法分为观察组（31例）和对照组（31例）。对照组患者给予亚低温治疗,观察组患者在亚低温治疗基础上给予依达拉奉辅助治疗14 d。比较2组患者的神经功能缺损评分和疗效,观察治疗前后患者的脑内凝血功能以及血清内NGF、CGRP含量的变化。 结果观察组患者的临床治疗有效率显著高于对照组（P<0.05）。观察组患者采用依达拉奉辅助亚低温治疗后颅内水肿面积显著降低,大脑中动脉平均血流速度明显升高,美国国立卫生研究院卒中量表评分水平显著下降,巴塞尔指数评定量表评分和GCS评分显著增高,差异有统计学意义（P<0.05）。观察组患者采用依达拉奉辅助亚低温治疗后NGF、CGRP水平明显升高,血浆D-二聚体、纤维蛋白原、凝血酶原时间、凝血酶原时间国际标准比值、活化部分凝血活酶时间、凝血酶时间显著下降,抗凝血酶显著上升,差异均有统计学意义（P<0.05）。 结论依达拉奉辅助亚低温治疗重型TBI的临床治疗效果较好,安全性较高,可有效恢复患者的凝血功能,促进NGF、CGRP表达。     

血清降钙素基因相关肽、5-羟色胺浓度与带状疱疹疼痛程度相关性分析

目的观察血清降钙素基因相关肽(CGRP)、5-羟色胺(5-HT)浓度与带状疱疹患者疼痛程度的相关性。方法选择2013年4月—2013年7月在我科住院的带状疱疹患者41例,采用视觉模拟评分(visual analogue scales,VAS)法进行疼痛评分,抽取外周静脉血分离血清,酶联免疫吸咐试验(ELISA)检测CGRP和5-HT,SAS软件分析VAS分值与血清CGRP、5-HT的相关性。结果 CGRP浓度与VAS分值呈负相关,相关系数为-0.763,P0.01;5-HT与VAS分值无相关性,相关系数为-0.171,P0.05。结论 CGRP可能对带状疱疹患者疼痛起着重要的调节作用,5-HT在带状疱疹疼痛的作用可能更为复杂。     

电针对颈上神经节切除脑缺血大鼠海马CGRP、NPY表达的影响

目的：观察电针对颈上神经节切除脑缺血大鼠海马降钙素基因相关肽（calcitonin generelated peptide,CGRP）及神经肽Y（neuropeptide Y,NPY）表达的影响,探讨电针水沟治疗缺血性脑血管疾病的作用机制。方法：将50只SD大鼠随机分为正常组、模型组、电针组、颈上神经节（superiorcervical ganglion,SCG）切除组、SCG切除十电针组,每组10只,采用链霉亲合素-生物素酶复合物法检测各组大鼠海马CGRP和NPY表达。结果：正常大鼠海马CGRP阳性神经细胞数量较少,模型组及SCG切除组CGRP阳性神经细胞数量显著增加;电针组、SCG切除＋电针组大鼠海马CGRP阳性神经细胞数量显著高于正常组、模型组和SCG切除组（P〈0．01）。模型组大鼠海马NPY阳性神经细胞数量较正常组明显增加（P〈0．01）,电针组、SCG切除组及SCG切除＋电针组大鼠海马NPY阳性神经细胞数量显著低于模型组（P〈0．01）。结论：SCG对海马NPY表达具有调控作用,电针可通过调节脑缺血大鼠海马神经肽的表达达到抗脑缺血损伤的作用。     

Two immunohistochemically identified populations of calcitonin gene-related peptide (CGRP)-immunoreactive axons in human skin

Double labelling immunofluorescence has shown two populations of unmyelinated sensory axons in human skin that contain immunoreactivity (IR) to calcitonin gene-related peptide (CGRP). One population also contains IR to substance P (SP), whilst the other also contains IR to somatostatin (SOM). Axons containing both CGRP-IR and SOM-IR comprised more than 75% of CGRP-IR axons associated with the epidermis; the rest of the CGRP-IR axons contained SP-IR. No axons contained both SP-IR and SOM-IR. Some dermal blood vessels were surrounded by axons containing both CGRP-IR and SP-IR, but most CGRP-IR perivascular axons contained SOM-IR without SP-IR. Sweat glands were well supplied with sensory axons containing CGRP-IR and weak SOM-IR but not SP-IR. Therefore, CGRP is a histochemical marker for a larger number of unmyelinated cutaneous afferents in human skin than is SP. CGRP itself may have a role in the mediation of responses to stimulation of at least two populations of sensory axons.