Characteristic methylation profile in CpG island methylator phenotype‐negative distal colorectal cancers

Aberrant DNA methylation is involved in colon carcinogenesis. Although the CpG island methylator phenotype (CIMP) is defined as a subset of colorectal cancers (CRCs) with remarkably high levels of DNA methylation, it is not known whether epigenetic processes are also involved in CIMP‐negative tumors. We analyzed the DNA methylation profiles of 94 CRCs and their corresponding normal‐appearing colonic mucosa with 11 different markers, including the five classical CIMP markers. The CIMP markers were frequently methylated in proximal CRCs (p < 0.01); however, RASSF1A methylation levels were significantly higher in distal CRCs, the majority of which are CIMP‐negative (p < 0.05). Similarly, methylation levels of RASSF1A and SFRP1 in the normal‐appearing mucosae of distal CRC cases were significantly higher than those in the proximal CRC cases (p < 0.05). They were also positively correlated with age (RASSF1A, p < 0.01; SFRP1, p < 0.01). Microarray‐based genome‐wide DNA methylation analysis of 18 CRCs revealed that 168 genes and 720 genes were preferentially methylated in CIMP‐negative distal CRCs and CIMP‐positive CRCs, respectively. Interestingly, more than half of the hypermethylated genes in CIMP‐negative distal CRCs were also methylated in the normal‐appearing mucosae, indicating that hypermethylation in CIMP‐negative distal CRCs is more closely associated with age‐related methylation. By contrast, more than 60% of the hypermethylated genes in CIMP‐positive proximal CRCs were cancer specific (p < 0.01). These data altogether suggest that CpG island promoters appear to be methylated in different ways depending on location, a finding which may imply the presence of different mechanisms for the acquisition of epigenetic changes during colon tumorigenesis.     

宫颈支持韧带内淋巴组织分布的研究

目的:研究淋巴组织在宫颈支持韧带内的分布。方法:切取9具女性尸体的宫颈支持韧带,采用HE染色、免疫组化染色的方法,观察淋巴组织在韧带内的分布特点。结果:9具标本中3具可在镜下见淋巴结共4枚。其中3枚位于宫颈旁2cm处主韧带头侧,1枚位于距宫颈4cm处宫骶韧带头侧。各韧带内的淋巴管特点相似。主韧带内淋巴管散在分布,宫骶韧带内的淋巴管较稀疏,主要分布在韧带的宫颈侧。膀胱宫颈韧带内仅偶见淋巴管。结论:宫颈支持韧带内淋巴组织分布较少,淋巴结主要位于主韧带中部头侧。     

Quantification of rhynchophylline in rabbit plasma by UPLC-MS/MS and its application in a pharmacokinetic study

It was recently revealed thatRhynchophylline (Rhy), an important constituent of Uncaria rhynchophylla, possessed antihypertensive and neuroprotective effects. However, no information about the pharmacokinetics of Rhy in a herbivorous speciessuch as rabbit is available. Allometric scaling is valuable in designing human pharmacokinetic parameters from preclinical species. To investigate the characteristics of Rhy in vivo, a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the measurement of Rhy concentrations in rabbit plasma. The method was linear over the concentration range of 0.01–10.24 µg/mL. Intra-day and inter-day precision and accuracy were less than 8.0%. The recoveries were in the range of 94.17%–103.32%. Matrix effects (ME) were minor. After oral administration of Rhy at 20, 40 and 80 mg/kg, the mean elimination half-life (t_1/2) for these doses were 1.19, 1.49 and 1.37 h in rabbits, respectively. There was a proportionate increase in the maximum concentration (C_max) and the area under the blood concentration-time curve (AUC_∞) for three doses. The developed method was suitable for the study on pharmacokinetics of Rhy after oral administration and it may provide a valuable basis for clinical application of such a bioactive compound of herbal medicines.     

彩色多普勒超声在儿童神经母细胞瘤化疗监测方面的应用价值

目的:评价彩色多普勒超声检查在儿童神经母细胞瘤化疗监测方面的临床价值。方法:收集27例经病理证实的腹部神经母细胞瘤患儿资料,分为手术组19例和非手术组8例,所有患儿于化疗前、后均行彩色多普勒超声检查,随访观察2-48个月,对比化疗前后的超声图像变化。结果:手术组19例患儿中,彩色多普勒超声显示肿瘤复发4例、手术后残留3例。定期化疗后4例（21.1%）病情好转,8例（42.1%）病情稳定,7例（36.8%）病情恶化;非手术组8例患儿中,彩色多普勒超声显示5例瘤体体积缩小,4例瘤体内钙化明显增多、密集分布,6例瘤体内血流减少,定期化疗后6例（75%）病情缓解,2例（25%）病情恶化。结论:彩色多普勒超声检查具有无电离辐射、可重复检查等特点,能清晰对比神经母细胞瘤化疗前后原发病灶、腹部器官转移及大血管等情况的变化,是儿童神经母细胞瘤化疗监测的重要检查方法。     

Impact of the polymorphism in vitamin D receptor gene BsmI and the risk of systemic lupus erythematosus

Clinical Rheumatology -     

Metadherin confers chemoresistance of cervical cancer cells by inducing autophagy and activating ERK/NF-κB pathway

Overexpression of metadherin (MTDH) has been reported in many solid tumors and implicated in chemoresistance. This study aimed to examine MTDH expression in cervical cancer tissues and explore its role in chemoresistance of cervical cancer. MTDH expression in cervical cancer biopsies and several cervical cancer cell lines was detected by immunoblotting and immunohistochemisty. MTDH expression level was experimentally modulated in HeLa cells to determine the effects on chemoresistance to cisplatin. The results showed that MTDH expression was higher in tissues from both cervical squamous carcinoma and cervical adenocarcinoma, compared to normal cervical tissues. MTDH expression was not correlated to patient age or cervical cancer grade, although nuclear MTDH expression was correlated with poor differentiation of cervical cancer. In SiHa, HeLa, CasKi, and C33A cells, MTDH expression level was positively correlated with chemoresistance to cisplatin. MTDH increased autophagy in HeLa cells, which was associated with decreased cleavage of Caspase-3 and the activation of EER/NF-κB pathway. In conclusion, MTDH expression is high in cervical cancer, and it contributes to chemoresistance of cervical cancer. MTDH could be utilized as a therapeutic target to overcome chemoresistance of cervical cancer.     

BOPPPS教学模式在《中药鉴定学》课程教学中的应用

BOPPPS教学模式是一种强调学生全方位参与和及时反馈交流的教学设计模式.该文以中药的案例讲解探讨了BOPPPS模式在《中药鉴定学》课程中的具体应用.     

子宫输卵管超声造影评价输卵管通畅性的临床研究

目的 探讨经阴道子宫输卵管超声造影(HyCoSy)评价输卵管通畅性的临床应用价值及其副反应情况.方法 对30例不孕症妇女行经阴道HyCoSy,其结果与腹腔镜直视下输卵管通染液术对照分析,分级评估其副反应情况.结果 与腹腔镜检查结果比较,HyCoSy诊断输卵管通畅性的敏感性、特异性、阳性预测值、阴性预测值及诊断符合率分别为91.7％、75.0％、84.6％、85.7％及85.0％,差异无统计学意义.30例患者中,副反应0级5例(16.7％),1级6例(20.0％),2级10例(33.3％),3级7例(23.3％),4级2例(6.7％),所有患者均无并发症发生.结论 经阴道HyCoSy可有效评价输卵管通畅性,且安全、无创,副反应较小,可用于临床评价不孕症患者输卵管通畅性的首选方法.     

Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas

Hepatocellular carcinoma (HCC) most commonly arises from chronic inflammation due to viral infection, as a result of genetic and epigenetic abnormalities. A global picture of epigenetic changes in HCC is lacking. We used methylated CpG island amplification microarrays (MCAMs) to study 6458 CpG islands in HCC and adjacent preneoplastic tissues [chronic hepatitis (CH) or liver cirrhosis (LC)] in comparison with normal liver tissues where neither viral infection nor hepatitis has existed. MCAM identified 719 (11%) prominent genes of hypermethylation in HCCs. HCCs arising from LC had significantly more methylation than those arising from CH (1249 genes or 19% versus 444 genes or 7%, P < 0.05). There were four patterns of aberrant methylation: Type I (4%, e.g. matrix metalloproteinase 14) shows a substantially high methylation level in adjacent tissue and does not increase further in cancer. Type II (55%, e.g. RASSF1A) shows progressively increasing methylation from adjacent tissue to HCC. Type III (4%, e.g. GNA14) shows decreased methylation in adjacent tissue but either similar or increased methylation in HCC. Type IV (37%, e.g. CDKN2A) shows low levels of methylation in normal tissue and adjacent tissue but high levels in HCC. These DNA methylation changes were confirmed by quantitative pyrosequencing methylation analysis in representative 24 genes and were analyzed for correlation with clinicopathological parameters in 38 patients. Intriguingly, methylation in the Type IV genes is characteristic of moderately/poorly differentiated cancer. Our global epigenome analysis reveals distinct patterns of methylation that are probably to represent different pathophysiologic processes in HCCs.