痰瘀同治方对心肌缺血再灌注损伤大鼠心肌Rho/Rho激酶通路的影响

目的 观察痰瘀同治方对高脂大鼠心肌缺血再灌注损伤（myocardial ischemic-reperfusion injury,MI/RI）Rho/Rho激酶信号转导通路的影响.方法 采用随机数字表法将60只SD雄性大鼠随机分为假手术组、模型组、西药对照组及痰瘀同治方高、低剂量组.可逆性冠脉左前降支结扎缺血30 min 再灌注2h复制MI/RI模型,应用RT-PCR及Western blotting法检测各组大鼠心肌RhoA、ROCK Ⅱ mRNA 表达及ROCK下游底物肌球蛋白轻链（MLC）磷酸化水平.结果 与模型组比较,痰瘀同治方低剂量组可降低心肌RhoA、ROCKⅡmRNA及磷酸化MLC （p-MLC）水平（P值分别为0.045、0.042、0.023,P均＜ 0.05）.结论 痰瘀同治方可通过抑制RhoA、ROCKⅡ激活及p-MLC蛋白过度表达而调控Rho/Rho激酶信号转导通路,发挥其对缺血再灌注损伤心肌的保护作用.     

Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia

Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME‐ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene‐based and pathway‐based analyses by applying the summary‐based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME‐ON and PLCO, after Bonferroni correction (p_pathway < 0.00625). The two most significant genes were NPAS2 (p_gene = 0.0062) and AANAT (p_gene = 0.00078); the latter being significant after Bonferroni correction. For colorectal cancer, we observed a suggestive association with the circadian rhythm pathway in GAME‐ON (p_pathway = 0.021); this association was not confirmed in GECCO (p_pathway = 0.76) or the combined data (p_pathway = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms.     

医疗健康知识图谱需求与技术构建研究

目的/意义调查不同群体对医疗健康知识图谱的需求,探讨知识图谱研究现状和不足,为医疗健康知识图谱的构建提出建议。方法/过程基于文献调查、问卷调研、专家访谈等方式,从数据来源、关键技术、应用场景、待改进之处等方面分析医疗健康知识图谱。结果/结论提出以国家政策为导向、以权威知识为依托,支持用户全程参与,注重个人隐私和知识产权保护,构建多场景、可视化、多语种、多模态的医疗健康知识图谱和易于知识传播的标准体系及底层数据规范制度。     

Evaluating a Model of Added Sugar Intake Based on Amino Acid Carbon Isotope Ratios in a Controlled Feeding Study of U.S. Adults

Previous studies suggest that amino acid carbon stable isotope ratios (CIR_AAs) may serve as biomarkers of added sugar (AS) intake, but this has not been tested in a demographically diverse population. We conducted a 15-day feeding study of U.S. adults, recruited across sex, age, and BMI groups. Participants consumed personalized diets that resembled habitual intake, assessed using two consecutive 7-day food records. We measured serum (n = 99) CIR_AAs collected at the end of the feeding period and determined correlations with diet. We used forward selection to model AS intake using participant characteristics and 15 CIR_AAs. This model was internally validated using bootstrap optimism correction. Median (25th, 75th percentile) AS intake was 65.2 g/day (44.7, 81.4) and 9.5% (7.2%, 12.4%) of energy. The CIR of alanine had the highest, although modest, correlation with AS intake (r = 0.32, p = 0.001). Serum CIR_AAs were more highly correlated with animal food intakes, especially the ratio of animal to total protein. The AS model included sex, body weight and 6 CIR_AAs. This model had modest explanatory power (multiple R² = 0.38), and the optimism-corrected R² was lower (R² = 0.15). Further investigations in populations with wider ranges of AS intake are warranted.     

Serum and tissue proteinase-like peptidase activities in women undergoing total mastectomy for breast cancer

Serum proteinase-like peptidases and proteinase inhibitor activities have been determined in 40 women with breast cancer at presentation and following total mastectomy. Activities of these enzymes have also been determined in homogenates of malignant (n = 13) and non-malignant (n = 11) breast tissue and benign breast lesions (n = 10). Following surgical treatment, the serum collagenase-like, cathepsin B-like and cathepsin H-like peptidase activities were significantly reduced. In addition, the activities of collagenase-like, cathepsin B-like and elastase-like peptidases were significantly higher in malignant breast tissue than in either non-malignant tissue from the same breast, or benign breast lesions. These findings are consistent with the suggestion that proteinases may have a role in tumour invasion.     

Ectopic production of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) by ovarian carcinoma

Human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) are placental proteins whose ectopic secretion by non-trophoblast tumours has been claimed to be of clinical relevance. Radioimmunoassays for hCG and hPL, together with human luteinising hormone (hLH), have been established and plasma levels were measured in 61 patients with carcinoma of the ovary. Approximately 51% of the patients were found to have raised plasma hCG levels. Such raised titres were not stage or tumour-type related but occurred only in post-menopausal subjects. The majority of patients with raised hCG levels also had raised plasma hLH levels. Assay cross-reactivity was shown to account for the ‘spurious’ hCG elevations. However, hCG may be an ectopic product in a minority of tumours; elevated plasma hCG levels were shown to coexist with low hLH levels. Although such lesions did not show morphologically identifiable choriocarcinomatous elements, all were poorly differentiated carcinomas. In some cells hCG was demonstrated by immunocytochemical methods. No patients had a raised plasma hPL level. It is concluded that these placental proteins are of no clinical use in the management of ovarian carcinoma patients.     

Subpleural pulmonary hamartoma: Demonstration by computed tomography

A case of a subpleural pulmonary hamartoma demonstrated by computed tomography is presented. The literature on subpleural pulmonary lesions demonstrated by computed tomography is reviewed. Although peripheral pulmonary hamartomas have been well documented, we believe this is the first demonstration of a subpleural location by computed tomography scanning. In the appropriate clinical setting, pulmonary hamartoma should be included in the differential diagnosis of subpleural lesions identified on computed tomography scanning of the chest.     

Immunohistochemical Localization of Basement Membrane Components and Interstitial Collagen Types in Preovulatory Rat Ovarian Follicles

Cryosections of ovaries from rats treated with pregnant mare serum gonadotropin (PMSG) were immunostained with antibodies against collagen types, I, III, IV and V, laminin and heparan sulphate proteoglycan using the peroxidase-antiperoxidase technique. A uniform belt-like staining was observed between the granulosa and theca interna layers with antibodies against type IV collagen, laminin and heparan sulphate proteoglycan.Interstitial collagens type I and III stained the connective tissue in the theca externa layer but gave only faint staining in the area between the granulosa and theca interna zones. If the PMSG-treated rats were injected with human chorionic gonadotropin the number of follicles that showed a discontinuous, ragged or disrupted staining reaction in the area between the granulosa and theca interna layers was clearly increased. Surprisingly in such cases also a punctate staining reaction was seen in the basal granulosa cells. When the rats were injected with radioactive human chorionic gonadotropin, most of the ovarian follicles were labeled within 2 hours. These follicles still showed a continuous staining reaction with antibodies against basement membrane components at the border of the granulosa and theca interna cell layers.These results suggest that there is a basement membrane-like structure in Graafian follicles between the granulosa cells and theca interna layer, and that this basement membrane is disrupted after human chorionic gonadotropin stimulation.     

The gene for staphylococcal protein A

Protein A from Staphylococcus aureus has become an important tool in immunology and molecular biology due to its specific binding to the constant region of immunoglobulins (Igs) from most mammalian species¹. Many qualitative and quantitative techniques have been developed which take advantage of this ‘pseudo-immune’ reaction². In addition, solid state protein A has recently been introduced in medical therapy to decrease the amount of circulating immune complexes in sera³. In this article Mathias Uhlén, Martin Lindberg and Lennart Philipson describe the structure of the protein A molecule and its gene. They also discuss the possibilities for fusing the protein A gene to other genes.