7.0T磁共振T2*-mapping在实验性自身免疫性脑脊髓炎脊髓病变中的应用

目的 应用超高场强MR T2^*-mapping序列定量评估实验性自身免疫性脑脊髓炎(EAE)动物模型的脊髓病变。方法 6~8周雌性C57BL/6小鼠,MOG_35-55诱导制备EAE模型10只(实验组),同龄健康对照组10只。在造模后第18天,分别对实验组和对照组脊髓行T2^*-mapping序列扫描,经后处理软件分析,比较实验组和对照组脊髓感兴趣区T2^*值的差异。结果 实验组第12天大鼠的体质量开始减轻,第14天神经学评分逐步增加。对照组体质量无明显减轻。MR T2^*加权像显示实验组脊髓内病灶呈不规则点片状稍高信号;对照组脊髓呈均匀等信号。T2^*值实验组[(12.66±1.78) ms]和对照组[(17.80±2.06)ms]差异有统计学意义(P<0.001),实验组各评分T2^*值之间差异无统计学意义(P>0.05)。结论 超高场强MR T2^*-mapping序列能够清晰显示小鼠脊髓病灶,并且可对病灶组织内铁含量进行定量测定,为EAE模型脊髓病变的无创检查提供新方法。     

Lymph node metastasis in T1 adenocarcinoma of the colon and rectum

The biology of colorectal cancer differs according to location within the large intestine. To evaluate the clinical significance of tumor location as a risk factor for lymph node metastasis (LNM), we performed a detailed pathological review of T1 adenocarcinomas of the colon and rectum. T1 adenocarcinomas of the colon and rectum treated by radical resection (n = 428) were identified from prospective clinical databases at two institutions. Tumor location was assigned as right colon (cecum to transverse), left colon (splenic flexure to sigmoid), or rectum (0–18 cm from AV). Pathology slides were reviewed, extent of submucosal invasion (sm width, sm depth) was quantified using an optical micrometer, and morphologic features of the cancer and its infiltrating margin were recorded. The overall rate of LNM was 10%. On univariate analysis, LNM was significantly more common in the rectum (27/176, 15%) compared to the left colon (13/160, 8%, p = .04) or right colon (3/92, 3%, p = .003). However, on multivariate analysis, deep submucosal invasion and lymphovascular invasion were independent and significant risk factors, whereas tumor location was not. T1 colorectal cancers have a progressively higher risk of LNM as their location becomes more distal. However, the increasing rate of LNM observed in cancers of the left colon and rectum is explained by a higher prevalence of high-risk pathologic features. In early colorectal cancers, tumor morphology is the strongest clinical predictor of metastatic behavior. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004     

Bioisosteric replacement of the pyrazole 5-aryl moiety of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A). A novel series of alkynylthiophenes as potent and selective cannabinoid-1 receptor antagonists

Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl moiety appended with an appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, as typified by compound 18, showed significant weight reduction in diet-induced obese mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB1-receptor homology model might exist in the binding site.     

氧化亚氮吸入清醒镇静在拔牙术中的止痛作用

实验组选取无笑气吸入禁忌证拔牙患者112例,随机分为60%笑气组61例,40%笑气组51例,在笑气吸入清醒镇静辅以局麻下拔牙;对照组53例,只在局麻下拨牙.结果表明:60%笑气组与40%笑气组的VAS疼痛评分大多较低,与对照组相比,在统计学上有非常显著性差异(P<0.001).提示笑气具有一定的镇静、止痛作用,联合局麻应用可以较好地控制患者焦虑与疼痛的复合状态.     

Identification of Patients with High-Risk Stage II Colon Cancer for Adjuvant Therapy

Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. Methods We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. Results With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1–6.2; P = 0.02), preoperative carcinoembryonic antigen >5 ng/ml (HR, 2.1; 95 percent CI, 1.1–4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1–4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent. Conclusions Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not avaliable.     

眼针疗法对腹泻型肠易激综合征模型大鼠结肠神经激肽1表达的影响

目的探讨眼针疗法对腹泻型肠易激综合征(D-IBS)的治疗作用及机制。方法将40只Wistar大鼠随机分为4组,对照组、模型组、匹维溴铵组和眼针组,每组10只。采用慢性应激结合束缚方法建立D-IBS模型,眼针组采用眼针治疗,针刺下焦区、大肠区、肝区、脾区;匹维溴铵组用匹维溴铵灌胃治疗,两组均治疗7天。HE染色观察结肠组织病理学变化;实时定量PCR测定结肠组织神经激肽1(NK1)的mRNA表达变化;免疫组化法测定结肠组织NK1的蛋白表达变化。结果各组大鼠结肠组织病理学无差异。与对照组比较,模型组结肠组织中NK1的mRNA表达水平显著升高(P<0.01);与模型组比较,眼针组结肠组织中NK1的mRNA表达水平显著降低(P<0.01);与模型组比较,匹维溴铵组结肠组织中NK1的mR-NA表达水平无统计学意义(P>0.05)。NK1免疫反应阳性细胞在结肠黏膜层、腺腔内、肌间神经丛、黏膜下神经丛等部位。与对照组比较,模型组结肠组织中NK1的蛋白表达水平显著升高(P<0.05);与模型组比较,眼针组和匹维溴铵组结肠组织中NK1的蛋白表达水平显著降低(P<0.05)。结论眼针能够降低D-IBS模型大鼠结肠组织中NK1的表达,从而对D-IBS起到治疗作用。     

基于数据挖掘探讨全国名中医王行宽诊疗胸痹心痛遣方用药规律及学术经验

目的：运用中医传承计算平台V3.0软件,研究王行宽教授治疗胸痹心痛遣方用药规律,传承王行宽教授诊疗胸痹心痛的学术经验。方法：收集整理2017—2020年王行宽教授于湖南中医药大学门诊诊疗冠心病心绞痛患者的原始病历资料,录入中医传承计算平台V3.0,运用软件进行方药规律研究。结果：共收集王行宽教授治疗胸痹心痛处方1 044则,所用药物多为甘、苦药物,归经以肺经为主,其次为心、脾、肝、胃、肾经;所用方剂中使用最多的经方是生脉散,最高的经验方是心痛灵Ⅲ号方;高频数药物主要有麦冬、半夏、丹参、瓜蒌皮、黄连、五味子、柴胡等药物;药物的常用剂量多为3、5、10、15 g;组方规律分析得到常用药组合129个,置信度>0.99的组合有58个,并得到常见证型核心药物;药物聚类得到6个核心药物组合。结论：王行宽教授论治胸痹心痛以益气养营、豁痰化瘀、疏肝利胆为治疗思路,并根据胸痹心痛不同证型予以辨证施治,体现其“多脏调燮、综合治理”的学术思想,其核心处方可供临床从业者参考,但仍需要进一步的临床及实验研究验证其疗效。     

Immunoblot analysis of c-Met expression in human colorectal cancer: Overexpression is associated with advanced stage cancer

c-Met, the receptor of hepatocyte growth factor is known to be responsible for the motility and mitogenesis of epithelial cells including cancer cells. To investigate the significance of c-Met expression in human colorectal cancer (CRC), total cellular protein, extracted from 130 CRCs were examined by Western blot analysis. The signal was quantitated by ChemiImager™ 4000 Low Light Imaging System. c-Met expression was analyzed as the ratio of tumor to matched normal tissue (T/N) and expressed as fold-increase. The cellular localization of c-Met was assessed by immunohistochemistry. The T/N fold increase of c-Met varied from 0.2 to 10.7 with a mean of 3.41 ± 0.23 (mean ± SE). 69% primary CRC showed overexpression (T/N >2.0) of c-Met. Significantly higher c-Met levels were found in CRC with blood vessel invasion (P = 0.04), and in advanced stage (P = 0.04). No relationship was noted between c-Met expression and age, tumor size, location, differentiation. C-Met immunoreactivity was observed in the membrane and cytoplasm of cancer cells. Positive staining of endothelial cells of blood vessels within normal submucosa and tumor was also evident. C-Met protein is expressed at levels significantly higher than adjacent mucosa in most primary adenocarcinomas of the colon. Our results support an important role for c-Met in human CRC progression and metastasis.