大鼠总基因甲基化状态改变相关危险因素的研究

目的：探讨高胆固醇血症（Hypercholesterolemia,HTC）对wistar大鼠主动脉基因组DNA总甲基化水平及总甲基转移酶活力的影响并比较高同型半胱氨酸血症（Hyperhomocysteinemia,HHCY）和HTC在影响主动脉基因组DNA总甲基化水平、总甲基转移酶活力之间的差异。方法：将wistar大鼠33只,随机分3 组：对照组、蛋氨酸组、高胆固醇组,每组11只。对照组给予普通大鼠饲料,其余各组给予相应的配方饲料。持续喂养3个月后心脏取血检测血清同型半胱氨酸（Homocysteine,Hcy）、总胆固醇（Total cholesterol,TC）等相关指标。提取主动脉基因组DNA检测基因组DNA总甲基化水平、提取主动脉核蛋白检测基因组DNA总甲基转移酶活力。结果：经多个样本均数间的多重比较（Dunnett-t检验）:高胆固醇组大鼠的血清TC水平明显高于对照组和蛋氨酸组,且差异有统计学意义（P＜0.05）,血清中甘油三酯（Triglyceride,TG）、低密度脂蛋白胆固醇（Low density lipoprotein-cholesterol,LDL-C）和高密度脂蛋白胆固醇（High density lipoprotein-cholesterol,HDL-C）,差异无统计学意义（P ＞0.05）。蛋氨酸组大鼠血清Hcy水平明显高于对照组及高胆固醇组,且差异有统计学意义（P＜0.05）。HHCY和HTC均增加基因组DNA总甲基转移酶活力,可促使基因组DNA去甲基化,与对照组相比,各组均具有统计学意义（P＜0.05）,但两组之间差异无显著性。结论：HTC降低大鼠主动脉基因组DNA总甲基化水平可能是HTC导致动脉粥样硬化发病重要机制之一,且HHCY和HTC在影响基因组DNA低甲基化之间的差异无显著。     

脂溢性角化病造模方法研究进展

脂溢性角化病是常见的皮肤良性肿瘤之一,病因及发病机制尚不清楚。为探索其发病机制及有效治疗药物,众多研究者建立了脂溢性角化病模型,如基因工程小鼠模型、紫外线诱导模型、异种移植模型、原代细胞模型等,现对近年来的模型作一综述。     

Analysis of Esophageal Motility and Reflux Characteristics in Patients with Gastroesophageal Reflux Disease With or Without Extraesophageal Symptoms

Background: The pathogenesis of extraesophageal symptoms of gastroesophageal reflux disease is complex, and esophageal motility and reflux may be involved in it. In this study, we aimed to compare esophageal motility and reflux characteristics in gastroesophageal reflux disease patients with and without extraesophageal symptoms by high-resolution manometry and multichannel intraluminal impedance-pH monitoring.Methods: We retrospectively studied gastroesophageal reflux disease patients between January 2014 and December 2018. All patients had undergone high-resolution manometry and multichannel intraluminal impedance-pH monitoring. The results were compared and analyzed.Results: A total of 59 patients were included in this study. Patients were divided into 3 groups according to their main complaint: only typical symptoms (group A, n = 11), both typical and extraesophageal symptoms (group B, n = 33), and only extraesophageal symptoms (group C, n = 15). Compared with group A, the lower esophageal sphincter basal pressure, integrated residual pressure, and lower esophageal sphincter length were lower, and the proximal reflux percentages of a weak acid and non-acid reflux were higher in group B and group C (P < .017). The positive rate of esophageal motility disorders was lower in group A than in other groups (P < .05). The proportion of patients with multiple rapid swallows/single swallow—distal contractile integral ratio greater than 1—was higher in group A than in other groups (P < .05).Conclusions: Decreased lower esophageal sphincter pressure and lower esophageal sphincter length, increased proximal esophageal reflux of weak acid and non-acid reflux, esophageal motility disorders, and decreased peristaltic reserve are involved in the pathogenesis of extraesophageal symptoms of gastroesophageal reflux disease.     

增免抑瘤颗粒剂干预卵巢癌大剂量化疗后免疫及骨髓抑制的实验研究

目的探讨增免抑瘤颗粒剂对卵巢癌SKOV3荷瘤小鼠顺铂（DDP）化疗后免疫及骨髓抑制的改善情况。方法建立卵巢癌SKOV3荷瘤小鼠模型,测定小鼠单次腹腔注射DDP的LD50。取40只造模成功的荷瘤鼠,随机分为DDP组、ZMYL高、中、低剂量合并DDP组,每组10只,各组均予DDP LD50值单次腹腔注射。注射后次日开始灌胃给药,ZMYL高、中、低剂量组的给药剂量分别为24.0g/kg、12.0g/kg、6.0g/kg,DDP组灌以等量的0.9%NaC l溶液,共干预8天。观察荷瘤小鼠存活时间、存活率、脾脏指数及骨髓DNA含量、血常规等指标变化情况,应用荧光标记的单克隆抗体染色结合流式细胞仪测定外周血T淋巴细胞亚群比例。结果①DDP腹腔注射LD50为16.36 mg/kg,95%可信限为13.22mg/k-20.39 mg/kg。②各组生存时间以及存活率差异均无统计学意义（P〉0.05）。③与DDP组比较,各剂量ZMYL＋DDP组均可提高荷瘤小鼠脾脏指数,中高剂量组还可提高骨髓DNA含量,差异均有统计学意义（P〈0.05）。④与DDP组比较,各剂量ZMYL＋DDP组均可提高荷瘤小鼠外周血中白细胞数,差异均有统计学意义（P〈0.05）。⑤与DDP组比较,各剂量ZMYL＋DDP组的CD3、CD4、CD8及CD4/CD8差异无统计学意义（P〉0.05）。结论 ZMYL对顺铂大剂量化疗引起的荷瘤小鼠外周血白细胞减少及骨髓DNA含量、脾脏指数的降低有明显的升高作用,能调节机体紊乱的免疫功能,改善骨髓抑制。     

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

ContextAsthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases.ObjectiveTo investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP.Materials and methodsForty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3β/mTOR signalling pathway.ResultsLKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13–65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway.Discussion and conclusionLKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.     

消抗汤治疗免疫性反复自然流产抗心磷脂抗体阳性46例

目的:观察消抗汤治疗免疫性反复自然流产抗心磷脂抗体阳性的临床疗效。方法:将65例免疫性反复自然流产抗心磷脂抗体阳性的患者,根据随机法按2:1分为试验组(46例,采用消抗汤加减治疗)和对照组(19例,采用阿斯匹林治疗),治疗8周后观察2组患者症状调查问卷评分和抗心磷脂抗体检验变化情况。结果:试验组46例,抗体转阴29例,有效率63.04%;对照组19例,抗体转阴6例,有效率31.58%;试验组治疗后的症状调查问卷平均积分与治疗前相比有显著下降,对照组治疗后的症状调查问卷平均积分与治疗前相比无显著差异。试验组总疗效明显优于对照组(P<0.05)。结论:通过临床试验观察表明,中药消抗汤对免疫性反复自然流产患者抗心磷脂抗体的转阴以及症状的改善具有显著的疗效,明显优于阿斯匹林的治疗效果。     

HPLC指纹图谱结合化学模式识别评价舒筋活血制剂的整体质量

目的建立舒筋活血制剂(舒筋活血胶囊、舒筋活血片)HPLC指纹图谱的方法,为其整体质量评价提供参考。方法色谱柱为Agilent Poroshell 120 SB-C18(150 mm×4.6 mm,2.7μm),以乙腈-0.2%甲酸水溶液为流动相,进行梯度洗脱;体积流量0.5mL/min,检测波长277nm,柱温30℃。采用"中药色谱指纹图谱相似度评价系统"(2012版)考察23批舒筋活血制剂的相似度,结合主成分分析(principal component analysis,PCA)、聚类分析(cluster analysis,CA)以及正交偏最小二乘判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)对舒筋活血制剂进行整体质量评价。结果舒筋活血制剂的HPLC指纹图谱中18批样品(S1～S17和S23)的相似度0.900,通过PCA、CA和OPLS-DA,23批样品聚成3类,S1～S16来自同一厂家为一类;S23和S17为一类;S18～S22为一类,并从10个共有峰中确定差异较大的4个共有峰,分别为1、3(5-羟甲基糠醛)、6(苯乙酸)和10(4-甲氧基水杨醛)号峰。结论所建立的指纹图谱结合化学模式识别方法稳定、简单,可用于评价舒筋活血制剂质量。     

子宫内膜异位症与抗碳酸酐酶抗体的关系

目的 :探讨抗碳酸酐酶Ⅰ、Ⅱ抗体与子宫内膜异位症的关系。方法 :应用酶联免疫吸附 (ELISA)法分别检测内异症 32例、其他妇科疾病 (妇科组 ) 2 0例及正常妇女 12例血清抗碳酸酐酶抗体水平。结果 :(1)内异症患者血清抗碳酸酐酶Ⅰ、Ⅱ抗体阳性率(87.5 %、5 3.1% )高于妇科组 (2 5 %、15 % ) ,两组差异有显著性 (P <0 .0 1) ;(2 )内异症患者血清抗碳酸酐酶Ⅰ、Ⅱ抗体阳性率明显高于正常妇女组 (0 %、0 % ) ,两组差异有显著性 (P<0 .0 1) ;(3)妇科组及正常妇女组血清抗碳酸酐酶Ⅰ、Ⅱ抗体阳性率较低 ,两组差异无显著性 (P >0 .0 5 )。结论 :检测抗碳酸酐酶抗体对诊断子宫内膜异位症及探讨其发病机制有重要价值