Wilson病治疗研究现状*

Wilson病(Wilson's disease,WD)是以铜代谢异常为病变特点的常染色体隐性遗传病,可引起病变器官,主要是肝脏和大脑,的继发性损伤。目前,主要的治疗方法是应用调节体内铜负平衡的药物,如螯合剂和锌盐等,具体药物的选择需根据患者的临床表现、对药物的耐受性、医师用药经验、药物成本和可及性等进行选择。由于WD的药物治疗需终身维持,且存在副作用和依从性问题,药物治疗具有一定的局限性。肝源缺乏、费用高昂和移植后需终身免疫抑制剂治疗等因素使肝移植治疗的应用也受到限制。所以,新型治疗药物或方法,特别是安全性更好和能够永久治愈的方法,引起了越来越多的关注。本文对WD的治疗研究现状进行了系统综述。     

Elevated blood pressure,cardiometabolic risk and target organ damage in youth with overweight and obesity

Background and aimTo compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines.Methods and resultsThis cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP ≥ 90th to <95th percentile for age, gender and height in children or BP ≥ 120/80 to <130/80 in adolescents. The overall prevalence of elevated BP was 18.3%, and significantly increased from normal-weight to obese youth. Young people with elevated BP showed higher levels of body mass index (BMI), insulin resistance and a higher prevalence of liver steatosis (45% vs 36%, p < 0.0001) than normotensive youth, whilst they did not differ for the other cardiometabolic risk factors, neither for carotid intima media thickness or left ventricular mass. Compared with normotensive youth, individuals with elevated BP had an odds ratio (95%Cl) of 3.60 (2.00–6.46) for overweight/obesity, 1.46 (1.19–1.78) for insulin-resistance and 1.45 (1.19–1.77) for liver steatosis, controlling for centers, age and prepubertal stage. The odds for insulin resistance and liver steatosis persisted elevated after correction for BMI-SDS.ConclusionCompared to normotensive youth, elevated BP is associated with increased BMI, insulin resistance and liver steatosis, without significant target organ damage.     

Research Progress on Prevention and Treatment of Glucolipid Metabolic Disease with Integrated Traditional Chinese and Western Medicine

Hyperlipidemia,type 2 diabetes mellitus,nonalcoholic fatty liver and many other metabolic disorder are frequently co-existing in patients.In addition,these diseases are closely related in pathophysiological settings.However,increasing of the disease incidence,lacking of comprehensive prevention and control measurements against the key pathology point concomitant occurrence with the pattern of the single disease,single target therapy,that is leading therapeutic strategy for these metabolic disorders in the setting of Western medicine(WM).On the basis of the combination of the advantages of integrated Chinese medicine(CM) and WM,with unified understanding of such diseases,the new concept of glucolipid metabolic disease(GLMD) is introduced.In this new concept,disorders in glucose and lipid metabolism are recognized as the key trigger and major driving force for the progress of GLMD.The key points of pathology included dysfunction of neuronal-endocrine-immune system,insulin resistance,oxidative stress,inflammation and intestinal flora imbalance.In the core pathogenic perspective of CM,it can be explained as "Gan(Liver) Shi Shu Xie"(dysfunction of Gan in metabolism and emotion regulation) that will lead to the occurence/production of endogenous dampness and phlegm,blood stasis and turbid.This leads to the new concept of "Liver-based regulatory system for metabolic homeostasis" to be introduced further.The comprehensive prevention and control strategy "Tiao Gan Qi Shu Hua Zhuo"(modulating Gan,trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness).Its representative formula Fufang Zhenzhu Tiaozhi Capsule(复方贞术调脂胶囊) is innovated under such rationales.Comment for some commonly-used CM GLMD therapeutic drugs was presented.High-level evidence-based and epidemiological and mechanism studies should be carried out to further interpret and explain of the scientific connotation of GLMD.     

橙皮苷对RAW264.7 巨噬细胞泡沫化及ICAM-1 表达的影响

目的：探讨橙皮苷对RAW264.7巨噬细胞泡沫化及细胞间黏附因子-1表达的影响。方法：体外培养RAW264.7 巨噬细胞,橙皮苷作用于未经诱导的RAW264.7 巨噬细胞及ox-LDL(50 μg?mL- 1）诱导后的RAW264.7巨噬细胞,将细胞分为空白对照组、ox-LDL模型组和橙皮苷给药组。MTT法检测不同浓度的橙皮苷对RAW264.7细胞活性的影响;用油红O染色观察橙皮苷对RAW264.7巨噬细胞内脂类堆积与泡沫细胞形成。观察橙皮苷对ox-LDL诱导RAW264.7巨噬细胞泡沫化的影响;免疫印迹法检测RAW264.7巨噬细胞中ICAM-1的蛋白表达。逆转录聚合酶链反应法检测RAW264.7巨噬细胞中ICAM-1的mRNA表达。结果：橙皮苷浓度大于或等于5 μM时,RAW264.7巨噬细胞存活率大于80%。橙皮苷抑制RAW264.7巨噬细胞泡沫化。橙皮苷能减少泡沫细胞的ICAM-1蛋白表达水平。橙皮苷能减少泡沫细胞ICAM-1 mRNA表达水平。结论：橙皮苷能抑制RAW264.7巨噬细胞泡沫化及ICAM-1的蛋白和mRNA表达,提示橙皮苷具有抗动脉粥样硬化临床应用价值。     

脐带间充质干细胞对肝星状细胞活化、凋亡的调控作用研究

目的观察人脐带间充质干细胞(UC-MSCs)对肝星状细胞LX-2活化和凋亡的影响,并分析其可能机制。方法体外分离、培养人UC-MSCs,将UC-MSCs与LX-2细胞按1:1和3:1比例进行混合共培养或Transwell共培养。通过流式细胞仪检测UC-MSCs对LX-2细胞活化、凋亡的影响。结果 HE、油红O、碱性磷酸酶染色及表型检测证实本实验所用UC-MSCs符合MSCs标准。LX-2细胞单独培养及与UC-MSCs混合共培养或Transwell共培养情况下,表达α-平滑肌肌动蛋白(α-SMA)的LX-2细胞比例分别为52.7%,43.9%(1:1)和34.2%(3:1),50.9%(1:1)和31.2%(3:1)。肝细胞生长因子(HGF)阻断实验未逆转UC-MSCs对LX-2细胞活化的抑制作用。与单独培养比较,LX-2细胞与UC-MSCs以1:1和1:3比例在Transwell共培养情况下,表达Annexin V单阳性的LX-2细胞比例由7.1%增加至14.9%和12.8%(P<0.01)。结论人UCMSCs可以抑制肝星状细胞系的活化并促进其凋亡,其抑制活化和促进凋亡不直接依赖于细胞间的相互接触,而是以细胞因子分泌的方式发生。     

LRH1 as a driving factor in pancreatic cancer growth

Liver receptor homolog 1 (LRH1), directs the development and differentiation of embryonic pancreas, and is overexpressed in pancreatic cancer (PC). We hypothesized that LRH1 promotes PC growth. Cell proliferation and tumorigenicity in nude mice were compared between empty vector-transfected (control) and stable LRH1-overexpressed PC cell lines. The subsequent tumor burden, vasculature development, and histologic features were evaluated. LRH1 overexpression enhanced the expression of downstream target genes (cyclin D1/E1) and stimulated cell proliferation in PC cell lines. LRH1 upregulated cyclin E1 truncated T1/T2 isoforms expression which may occur through ERα–calpain1 signaling. Compared with the control, LRH1 overexpressing stable cells generated tumors with increased weight, proliferation index and enhanced angiogenesis. Cyclin D1/E1 and calpain1 were overexpressed in human PC tumors compared to adjacent normal pancreas. These observations demonstrate that LRH1 promotes PC growth and angiogenesis, suggesting that LRH1 is a driving factor in tumorigenesis and may serve as a potential therapeutic target.     

西藏地区273例肝包虫病临床分析

目的探讨肝包虫病的临床特点及手术方式,提高手术治愈率。方法回顾性分析西藏地区273例经手术确诊为肝包虫病患者的临床特点,总结手术治疗经验。结果全部患者均顺利完成手术,无术中死亡。术后发生切口感染10例,胆瘘23例(8.4%),包虫复发41例。平均住院日23.0±8.0 d。结论肝包虫病的治疗以手术为主,手术方式由病情决定,原则为彻底消灭外囊残腔,减少并发症,提高患者生活质量。