多药耐药基因多态性对利培酮及9-羟基利培酮稳态血药浓度的影响

多药耐药基因(MDR1)是跨膜转运体P-糖蛋白(P-gp)的编码基因。胃肠道和血脑屏障等组织中的P-gp可以将包括药物在内的外源性底物排出细胞,影响P-gp底物药物的吸收和分布。MDR1基因多态性会影响P-gp表达和活性,进而影响底物药物的血药浓度和临床疗效,非典型性抗精神药物利培酮及代谢物9-羟基利培酮都是P-gp底物,MDR1基因多态性与这类药物的血药浓度和临床疗效可能相关。     

飞机草-裸花紫珠配伍用于动物外伤止血及抗炎的药效学研究

目的 观察飞机草-裸花紫珠配伍用于外伤止血及抗炎的药效学.方法 采摘飞机草地上部分和裸花紫珠叶,制成飞机草-裸花紫珠1∶4配伍的粉末及水煎液.将其用于新西兰兔耳缘动脉止血、体内外凝血、二甲苯所致小鼠炎症的抗炎实验;观察其对角叉菜胶致小鼠足跖肿胀组织中前列腺素E2(PGE2)、5-羟色胺(5-HT)、丙二醛(MDA)及组胺含量的影响,对新西兰兔血凝血酶原时间、活化部分凝血活酶时间(APTT)、凝血酶时间、纤维蛋白原(FIB)的影响,并观察对小鼠毛细血管通透性的影响.结果 飞机草-裸花紫珠1∶4配伍联用能显著缩短出血时间、凝血时间和APTT,且上述时间短于单用飞机草或裸花紫珠(P＜0.05).飞机草-裸花紫珠水煎液1∶4配伍联用的肿胀度抑制率、毛细血管通透性抑制率和FIB明显升高,且高于单用飞机草或裸花紫珠(P＜0.05).飞机草-裸花紫珠水煎液1∶4配伍联用能显著降低炎症组织中PGE2、5-HT及MDA的水平,且低于单用飞机草(P＜0.05).结论 飞机草与裸花紫珠1∶4配伍较单用飞机草、裸花紫珠具有更好止血抗炎作用.     

Ampelopsin‐induced autophagy protects breast cancer cells from apoptosis through Akt‐mTOR pathway via endoplasmic reticulum stress

Our previous study has shown that ampelopsin (AMP), a flavonol mainly found in Ampelopsis grossedentata, could induce cell death in human breast cancer cells via reactive oxygen species generation and endoplasmic reticulum (ER) stress pathway. Here, we examined whether autophagy is activated in AMP‐treated breast cancer cells and, if so, sought to find the exact role and underlying molecular profile of autophagy in AMP‐induced cell death. Our results showed that AMP treatment activated autophagy in MDA‐MB‐231 and MCF‐7 breast cancer cells, as evidenced by the accumulation of autophagosomes, an increase of microtubule‐associated protein 1 light chain 3 beta‐2 (LC3B‐II) and the conversion of LC3B‐I to LC3B‐II, the degradation of the selective autophagic target p62/SQSTM1, and the formation of green fluorescent protein (GFP)‐LC3 puncta. Blockage of autophagy augmented AMP‐induced cell death, suggesting that autophagy has cytoprotective effects. Meanwhile, AMP treatment suppressed Akt‐mammalian target of rapamycin (mTOR) pathway as evidenced by dose‐ and time‐dependent decrease of the phosphorylation of Akt, mTOR and ribosomal protein S6 kinase (p70S6K), whereas Akt activator insulin‐like growth factor‐1 (IGF‐1) pretreatment partially restored Akt‐mTOR pathway inhibited by AMP and decreased AMP‐inuduced autophagy, signifying that AMP activated autophagy via inhibition of the Akt‐mTOR pathway. Additionally, blocking ER stress not only reduced autophagy induction, but also alleviated inhibition of the Akt‐mTOR pathway induced by AMP, suggesting that activation of ER stress was involved in induction of autophagy and inhibition of the Akt‐mTOR pathway. Taken together, these findings indicate that AMP induces protective autophagy in human breast cancer cells through Akt‐mTOR pathway via ER stress.     

糙叶五加茎化学成分研究

目的基于脂多糖(LPS)诱导的巨噬细胞RAW264.7和小胶质细胞BV2为生物活性导向模型研究糙叶五加Acanthopanax henryi茎的化学成分。方法采用硅胶柱色谱、凝胶柱色谱、制备薄层及重结晶等方法进行分离纯化,利用波谱分析结合理化性质鉴定化合物的结构。结果从糙叶五加茎甲醇提取物的醋酸乙酯萃取部位中分离得到18个化合物,分别鉴定为对羟基苯甲酸(1)、反式对羟基肉桂酸(2)、反式咖啡酸甲酯(3)、咖啡酸(4)、反式松柏醛(5)、丁香醛(6)、香草醛(7)、6-甲氧基-7-羟基香豆素(8)、反式芥子醛(9)、十一烷二酸单甲酯(10)、(-)-芝麻素(11)、3-O-咖啡酰奎宁酸(12)、5-O-咖啡酰奎宁酸(13)、1,3-双咖啡酰奎宁酸(14)、1,4-双咖啡酰奎宁酸(15)、1,5-双咖啡酰奎宁酸(16)、豆甾醇(17)、β-谷甾醇(18)。结论化合物10为首次从五加科植物中分离得到;除化合物12、14、17、18外,其他化合物均为首次从该植物中分离得到。     

Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications for regional vulnerability in Alzheimer's disease

Studies of acetylcholine degrading enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in Alzheimer's disease (AD) have suggested their potential role in the development of fibrillar amyloid‐β (Aβ) plaques (amyloid plaques). A recent genome‐wide association study analysis identified a novel association between genetic variations in the BCHE locus and amyloid burden. We studied BChE immunoreactivity in hippocampal tissue sections from AD and control cases, and examined its relationship with amyloid plaques, neurofibrillary tangles (NFT), dystrophic neurites (DN) and neuropil threads (NT). Compared to controls, AD cases had greater BChE immunoreactivity in hippocampal neurons and neuropils in CA2/3, but not in the CA1, CA4 and dentate gyrus. The majority of amyloid plaques (> 80%, using a pan‐amyloid marker X‐34) contained discrete neuritic clusters which were dual‐labeled with antibodies against BChE and phosphorylated tau (clone AT8). There was no association between overall regional BChE immunoreaction intensity and amyloid plaque burden. In contrast to previous reports, BChE was localized in only a fraction (~10%) of classic NFT (positive for X‐34). A similar proportion of BChE‐immunoreactive pyramidal cells were AT8 immunoreactive. Greater NFT and DN loads were associated with greater BChE immunoreaction intensity in CA2/3, but not in CA1, CA4 and dentate gyrus. Our results demonstrate that in AD hippocampus, BChE accumulates in neurons and plaque‐associated neuritic clusters, but only in a small proportion of NFT. The association between greater neurofibrillary pathology burden and markedly increased BChE immunoreactivity, observed selectively in CA2/3 region, could reflect a novel compensatory mechanism. Since CA2/3 is generally considered more resistant to AD pathology, BChE upregulation could impact the cholinergic modulation of glutamate neurotransmission to prevent/reduce neuronal excitotoxicity in AD hippocampus.     

Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study

Journal of Gastroenterology - Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed...     

Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers

The succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”.     

Anorexia and adipsia: dissociation from fever after MIP-1 injection in ventromedial hypothalamus and preoptic area of rats.

Certain cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1) act centrally to affect eating behavior and thermoregulation and may be involved in the physiological mechanisms leading to anorexia, adipsia and loss in body weight. The newly discovered macrophage inflammatory protein-1 (MIP-1) infused into the anterior hypothalamic, preoptic area (AH/POA) evokes an intense hyperthermia. The present experiments were designed to determine whether MIP-1 affects the feeding mechanism in the ventromedial hypothalamus (VMH) independently of the thermoregulatory mechanism in the AH/POA. For the microinjection of MIP-1, guide cannulae were implanted stereotaxically in the rat just above the VMH or AH/POA. Following postoperative recovery, each unrestrained rat was adapted to procedures whereby body temperature and intakes of food and water available ad lib were monitored at predetermined intervals. When an efficacious dose of 5.6 picograms (pg) MIP-1 was microinjected in a volume of 0.5 microliters into the VMH, the intake of food in the rat was reduced significantly in the short term and throughout the following 22 h. Within intervals of 30 min and 4.0 h following MIP-1, the amount of food consumed was 4.0 and 10 g, respectively, below that eaten by control rats given the saline solvent vehicle injected at the same site in the VMH. Over the entire test period, the intake of water was similarly significantly below that of the control rats. Whereas MIP-1 injected into the AH/POA evoked fever accompanied by a transient decline in feeding, the body temperature of the rats was unaffected by the cytokine injected in the VMH.(ABSTRACT TRUNCATED AT 250 WORDS)     

贵州省15岁及以上人群高血压患病率及分布调查

目的 了解贵州省≥15岁人群高血压患病及分布情况,为贵州省高血压防治工作提供依据。方法 2014年9月至2015年10月采用分层多阶段随机抽样方法确定研究对象,采用全国统一的调查问卷进行面对面访谈式调查,血压测量采用欧姆龙HEM-1300电子血压计。采用SPSS 19.0软件进行分析,率的比较采用χ²检验,高血压患病影响因素分析采用多因素logistic回归分析。结果 共调查13 480人,男性5 509人（40.8%）,女性7 971人（59.2%）;城市6 558人（48.6%）,农村6 922人（51.4%）;吸烟3 232人（23.9%）,饮酒2 412人（17.9%）,肥胖和超重4 859人（36.0%）。高血压患者3 937人（29.2%）,高血压标化患病率分别为18.97%（全国）和21.16%（贵州省）。男、女性高血压患病率分别为29.8%和28.8%;农村和城市人群高血压患病率分别为35.8%和22.2%,差异有统计学意义（P<0.001）。≥65岁老年人群高血压患病率为56.2%。吸烟人群和不吸烟人群高血压患病率分别为34.3%和27.6%。饮酒人群和不饮酒人群高血压患病率分别为39.2%和27.0%。肥胖和超重人群及正常体重和体重较轻人群高血压患病率为40.7%及22.7%。不同城乡、年龄、文化程度、吸烟情况、饮酒情况及BMI人群的高血压患病率的差异有统计学意义（P<0.001）。结论 贵州省高血压患病率处于较高水平,农村人群高血压患病率高于城市人群。高血压患病率随年龄增长呈显著上升,总体显示文化程度越高,高血压患病率降低。高龄、居住农村、吸烟、饮酒、肥胖为高血压危险因素。     

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878