Genome variation in colorectal cancer patient with liver metastasis measured by whole-exome sequencing

BackgroundLiver metastasis of colorectal cancer (CRC) is an important cause of death from CRC, but its molecular mechanism is still unclear. In recent years, whole-exome sequencing has played an increasingly important role in the study of the occurrence and development of diseases, especially malignant tumors. Its high throughput and low cost advantages enable researchers to explore the pathogenic genes of diseases, and screen potential molecular markers and therapeutic targets from the level of genomics.MethodsThis study collected the primary tumor tissues, matched paracancerous, normal tissues, and liver metastases of 4 CRC patients admitted to the Department of General Surgery of the First Affiliated Hospital of Soochow University, and performed high-depth whole-exome sequencing, with the sequencing depth of each sample reaching 123× on average, then filtered the sequencing data, compared them, and analyzed the bioinformatics data.Resultswe found 8,565 single nucleotide variants (SNV) and 429 insertions/deletions (InDel) in the primary and hepatic lesion tissues, and the genes with the highest mutation frequency were titin (TTN), obscurin (OBSCN), and homeodomain-interacting protein kinase 2 (HIPK2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the mutant genes was conducted, and it was found that the mutant genes were mainly concentrated in the cells, cell parts, and cellular process of GO. The results of KEGG pathway analysis showed that mutations were mainly distributed in circadian entrainment, insulin secretion, and glutamatergic synapse. Further, we identified 723 SNV and Indel genes with high frequency mutations including TTN, OBSCN, and hydrocephalus-inducing protein homolog (HYDIN) across all tissues of liver metastases. The GO analysis showed that the mutated genes in liver metastatic tissues were mainly concentrated in cell, cell part, and cellular process. The KEGG pathway analysis showed that high frequency mutation genes were focused on gastric acid secretion, bile secretion, and melanogenesis.ConclusionsThis study found some candidate genes related to the occurrence of CRC and liver metastasis through whole-exome sequencing of relevant tissues in CRC patients with liver metastasis, which is expected to provide new markers and therapeutic targets for such patients.     

川芎嗪对离体豚鼠气道平滑肌的效应及机制研究

目的：探讨川芎嗪( ligustrazine,LIG)对离体豚鼠气道平滑肌( airway smooth muscle,ASM)的效应及机制。方法取正常豚鼠支气管,制作成气管螺旋条,随机分成LIG组、LIG+普萘洛尔组、LIG+阿托品组、LIG+硝苯地平组、LIG+格列苯脲组、对照组。分别观察ASM在静息张力下以及组胺所致的高张力下,各组不同LIG浓度对ASM的效应并比较各组间ASM舒张率。结果(1) LIG对离体豚鼠ASM静息张力以及组胺所致的高张力均具有舒张作用。(2)离体豚鼠ASM在静息张力下,与LIG组比较,LIG+普萘洛尔组在LIG浓度10-7~10-6．5 mol/L时,舒张作用明显受到拮抗( P <0．05)。 LIG +阿托品组、LIG+格列苯脲组在LIG浓度10-7．5~10-3 mol/L时,舒张作用没有明显差别(P>0．05)。 LIG+硝苯地平组在LIG浓度10-6~10-4 mol/L时,舒张作用明显加强( P<0．05)。(3)离体豚鼠ASM在组胺所致的高张力下,与LIG组比较,LIG+普萘洛尔组在LIG浓度10-6.5~10-5 mol/L时,舒张作用明显受到拮抗( P<0．05);LIG+阿托品组、LIG+格列苯脲组在LIG浓度10-8~10-3 mol/L时,舒张作用没有明显差别( P>0．05);LIG+硝苯地平组在LIG浓度10-6.5~10-5 mol/L时,舒张作用明显加强(P<0．05)。结论 LIG可对离体豚鼠ASM静息张力以及组胺所致的高张力产生明显的舒张作用,其效应的产生可能与竞争性激动β2受体以及抑制Ca2+内流有关,这为临床应用川芎嗪治疗支气管哮喘提供了理论依据。     

Erk1/2 signalling is involved in the differentiation of periodontal ligament stem cells to Schwann cells in dog

Periodontal ligament stem cells (PDLSCs) show a multi-differentiation potential, however, the mechanism of its neural differentiation is still unclear. We aim to explore the potential role of Erk1/2 signalling pathway in the differentiation of PDLSCs to Schwann cells (SCs).     

心脏介入性治疗失败后急诊手术的围术期处理

心脏介入性治疗失败后造成严重并发症需急诊手术治疗者7例，其中术前经皮二尖瓣成形术5例；经皮冠状动脉成形术2例，并发心源性休克4例；术后死亡4例。处理好围手术期间诸环节是手术成功的关键，术前尽最大努力避免心源性休克的发生，术中加强心肌保护以及尽早实施脑保护措施对减少手术早期死亡率有重要意义。     

17β-雌二醇对去卵巢SD大鼠离体骨组织微损伤的影响

目的 :观察 17β 雌二醇对不同时期去卵巢SD大鼠离体骨组织微损伤的影响 ,评价抗骨质疏松药物的防治效果及评价指标。方法 :10月龄SD大鼠 90只 ,随机分为 3组各 30只 ,每组分成去卵巢组 (OVX组 )、17β 雌二醇替代组(EST组 )和对照组 (SHAM组 ) 3个小组 ,分别于去卵巢后 3、15和 2 1周时处死大鼠 ,右侧胫骨上端行常规骨形态计量学观察 ,对第 4离体椎骨进行疲劳损伤后观测微损伤。结果 :疲劳损伤后每块骨组织磨片均可见微损伤 ,以微破裂最常见 ,各组间及小组间比较差异均无显著性。骨小梁单位面积百分率微破裂长度和数目在 3周时出现OVX组明显低于EST组 ,与SHAM组比较差异无显著性 (P >0 0 5 ) ;15周时 3组差异消失 ,2 1周时OVX组明显大于其它 2组 (P <0 0 5 ) ,EST组与SHAM组比较差异均无显著性 (P >0 0 5 )。结论 :10月龄SD大鼠去卵巢后早期尚不表现出骨结构性能的下降 ,17β 雌二醇早期应用可使骨结构性能提高 ,且应用至去卵巢后较晚时期显示出良好的抗骨结构性能下降效果。单位骨小梁面积百分率的微破裂长度和数目可反映药物对骨质疏松的影响 ,可作为骨结构性能的评价指标。观察时间以去卵巢后 2 1周较佳。     

Statin therapy for cardiac hypertrophy and heart failure.

Cardiac hypertrophy leading to heart failure is a major cause of morbidity and mortality worldwide. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been shown to inhibit cardiac hypertrophy and improve symptoms of heart failure by cholesterol-independent mechanisms. Statins block the isoprenylation and function of members of the Rho guanosine triphosphatase family, such as Rac1 and RhoA. Because Rac1 is a requisite component of reduced nicotinamide adenine dinucleotide phosphate oxidase, which is a major source of reactive oxygen species in cardiovascular cells, the ability of statins to inhibit Rac1-mediated oxidative stress contributes importantly to their inhibitory effects on cardiac hypertrophy. Furthermore, inhibition of RhoA by statins leads to the activation of protein kinase B/Akt and up-regulation of endothelial nitric oxide synthase in the endothelium and the heart. This results in increased angiogenesis and myocardial perfusion, decreased myocardial apoptosis, and improvement in endothelial and cardiac function. Because these effects of statins occur independently of cholesterol lowering, statins may have therapeutic benefits in nonhyperlipidemic patients with cardiac hypertrophy and heart failure.     

大黄素次酸对皮肤黑素细胞一氧化氮合酶的调控作用及意义

背景:在影响黑素细胞功能的诸多信号介导途径中,一氧化氮被认为是一种极为重要的信号分子。大黄有效成分大黄素次酸可以影响黑素细胞的增殖及调节细胞中酪氨酸酶的活性。目的:观察大黄有效成分大黄素次酸对豚鼠皮肤黑素细胞的一氧化氮合酶表达的影响,以期确定大黄在活体皮肤中对黑素细胞的黑素合成的有效作用浓度和作用机制。设计:完全随机分组设计,对照实验。单位:泸州医学院附属医院皮肤科。材料:实验于2004-01/06在泸州医学院附属医院传染科实验室和泸州医学院组织学与胚胎学实验室完成。选用成年健康雄性封闭群豚鼠24只。随机将豚鼠分为6组:对照组,大黄素次酸2,5,10,20,40mg/L组,每组4只。方法:①将大黄素次酸用二甲基亚砜溶解稀释为2,5,10,20,40mg/L,分别对大黄素次酸(中国生物医学制品检定所提供,该药品为实验室提取的白色粉末纯品)2,5,10,20,40mg/L组豚鼠臀部、背部两处局部皮肤进行相应质量浓度皮下注射处理,注射量均为1mL。24h后对其中一处皮肤加注1mL相同浓度大黄素次酸一次。48h后取材,常规石蜡切片(取对照组及大黄素次酸组未注射药物处皮肤作实验对照组)。②免疫组织化学方法法显示一氧化氮合酶的表达,用光学显微镜在高倍镜下观察,识别黑素细胞,观察细胞胞质的染色及特点。用MLAS-1000图像分析仪,每组随机选择5张切片,每张切片检测20个细胞,由计算机处理系统计算出各组黑素细胞胞质中阳性免疫产物的平均吸光度(A值)。③计量资料差异比较采用方差分析,并且用SNK-q进行组间比较。主要观察指标:免疫组织化学方法显示黑素细胞内一氧化氮合酶的表达,用光学显微镜和图像分析仪获得实验结果。结果:黑素细胞胞质中阳性免疫产物的平均A值:大黄素次酸2,5,10,20,40mg/L组明显低于实验对照组(0.126±0.118,0.103±0.082,0.118±0.097,0.122±0.095,0.112±0.078,0.196±0.066,P<0.05);大黄素次酸各质量浓度组间差异不明显(P>0.05)。结论:①大黄素次酸对黑色素细胞一氧化氮合酶的表达具有调节作用,提示大黄对黑素细胞的调节通过一氧化氮信号传导通路。②大黄素次酸在2～40mg/L的质量浓度内,一氧化氮合酶的表达不随大黄素次酸的质量浓度改变而发生变化。