骨性关节炎与类风湿关节炎的股骨近端骨结构三维微观结构分析（英文）

背景:人工关节假体松动的原因除了手术技术、假体设计及其产生的磨损颗粒等因素以外,假体周围的骨质量也起着极为重要的作用。骨微观结构是影响骨质量主要因素,应用技术分析组织微观结构目前已初步用于各种骨骼疾病的研究。目的:应用micro-CT技术,观察类风湿性关节炎与骨性关节炎股骨近端骨组织性能变化,对比研究两者之间的骨微观结构差异。方法:收集原发性骨关节病和类风湿性关节炎患者因行全髋关节置换而切除的股骨头(骨性关节炎10个,类风湿关节炎7个)。根据每个股骨头标本X射线上主要骨小梁方向,取材并制作来自于股骨颈骨组织的10 mm标本,然后进行micro-CT扫描,数据转换成3D图像数据后,分析两组之间皮质骨、松质骨以及股骨颈整体的骨微结构参数,做统计学处理。结果与结论:骨性关节炎与类风湿性关节炎的股骨颈骨组织的微结构(皮质骨、松质骨以及整体)差异无显著性意义;两种疾病的股骨颈骨组织的整体微结构特点与松质骨结构特点相近。与类风湿患者相比,骨关节炎患者骨小梁的连接性密度丢失较多,皮质骨的骨小梁定向分布程度升高,而松质骨和整体的骨小梁定向分布程度降低。结果证实,骨性关节炎与类风湿性关节炎的皮质骨、松质骨以及整体股骨颈骨组织的微结构无显著差异,这提示两种疾病的股骨颈整体的微结构退变是相同的。     

Why cuckoos should parasitize parrotbills by laying eggs randomly rather than laying eggs matching the egg appearance of parrotbill hosts?

The coevolutionary interaction between cuckoos and their hosts has been studied for a long time, but to date some puzzles still remain unsolved. Whether cuckoos parasitize their hosts by laying eggs randomly or matching the egg morphs of their hosts is one of the mysteries of the cuckoo problem. Scientists tend to believe that cuckoos lay eggs matching the appearance of host eggs due to selection caused by the ability of the hosts to recognize their own eggs.In this paper, we first review previous empirical studies to test this mystery and found no studies have provided direct evidence of cuckoos choosing to parasitize host nests where egg color and pattern match. We then present examples of unmatched cuckoo eggs in host nests and key life history traits of cuckoos, e.g. secretive behavior and rapid egg-laying and link them to cuckoo egg laying behavior. Finally we develop a conceptual model to demonstrate the egg laying behaviour of cuckoos and propose an empirical test that can provide direct evidence of the egg-laying properties of female cuckoos. We speculate that the degree of egg matching between cuckoo eggs and those of the host as detected by humans is caused by the ability of the hosts to recognize their own eggs, rather than the selection of matching host eggs by cuckoos. The case of Common Cuckoos(Cuculus canorus) and their parrotbill hosts(Paradoxornis alphonsianus), where it has been shown that both have evolved polymorphic eggs(mainly blue and white), was used to develop a conceptual model to demonstrate why cuckoos should utilize parrotbill hosts by laying eggs randomly rather than laying eggs matching the appearance of host eggs.In conclusion, we found no evidence for the hypothesis that cuckoos lay eggs based on own egg color matching that of the parrotbill-cuckoo system. We argue theoretically that laying eggs matching those of the hosts in this system violates a key trait of the life history of cuckoos and therefore should be maladaptive.     

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes

AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.     

Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients

AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon(peg-INF) α2a + ribavirin(PR) according to standard treatment schedules without randomization.These patients were treated in routine practice settings in 10 public or private health care centers,and the data were prospectively collected.Only patients with severe liver fibrosis(Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography),genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.RESULTS:The Metavir fibrosis scores were F3 in 35(28%) and F4 in 90(72%) of the patients.In total,62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy.The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%.The SVR was 65.9% in the TPV group and 44.1% in the BOC group.Independent predictive factors of an SVR included a response to previous treatment,relapsers vs null-responders [OR = 3.9;(1.4,10.6),P = 0.0084],a rapid virological response(RVR) [OR 6.9(2.6,18.2),P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2(2.3,29.5),P = 0.001].During treatment,63 patients(50.8%) had at least one severe adverse event(SAE) of grade 3 or 4.A multivariate analysis identified two factors associated with SAEs:female gender [OR = 2.4(1.1,5.6),P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3(2.3,12.4),P ≤ 0.001].CONCLUSION:More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting.The SVR rate was influenced by the response to previous PR treatment,the RVR and liver stiffness.     

Virtual chromoendoscopy in small bowel capsule endoscopy: New light or a cast of shadow?

AIM: To evaluate whether virtual chromoendoscopy can improve the delineation of small bowel lesions previously detected by conventional white light small bowel capsule endoscopy(SBCE). METHODS: Retrospective single center study. One hundred lesions selected from forty-nine consecutive conventional white light SBCE(SBCE-WL) examinations were included. Lesions were reviewed at three Flexible Spectral Imaging Color Enhancement(FICE) settings and Blue Filter(BF) by two gastroenterologists with ex-perience in SBCE, blinded to each other's findings, whoranked the quality of delineation as better, equivalent or worse than conventional SBCE-WL. Inter-observer percentage of agreement was determined and analyzed with Fleiss Kappa(k) coefficient. Lesions selected for the study included angioectasias(n = 39), ulcers/ero-sions(n = 49) and villous edema/atrophy(n = 12). RESULTS: Overall, the delineation of lesions was im-proved in 77% of cases with FICE 1, 74% with FICE 2, 41% with FICE 3 and 39% with the BF, with a percent-age of agreement between investigators of 89%(k = 0.833), 85%(k = 0.764), 66%(k = 0.486) and 79%(k = 0.593), respectively. FICE 1 improved the delineation of 97.4% of angioectasias, 63.3% of ulcers/erosions and 66.7% of villous edema/atrophy with a percentage of agreement of 97.4%(k = 0.910), 81.6%(k = 0.714) and 91.7%(k = 0.815), respectively. FICE 2 improved the delineation of 97.4% of angioectasias, 57.1% of ulcers/erosions and 66.7% of villous edema/atrophy, with a percentage of agreement of 89.7%(k = 0.802), 79,6%(k = 0.703) and 91.7%(k = 0.815), respectively. FICE 3 improved the delineation of 46.2% of angioecta-sias, 24.5% of ulcers/erosions and none of the cases of villous edema/atrophy, with a percentage of agreement of 53.8% [k = not available(NA)], 75.5%(k = NA) and 66.7%(k = 0.304), respectively. The BF improved the delineation of 15.4% of angioectasias, 61.2% of ulcers/erosions and 25% of villous edema/atrophy, with a per-centage of agreement of 76.9%(k = 0.558), 81.6%(k = 0.570) and 25.0%(k = NA), respectively.CONCLUSION: Virtual chromoendoscopy can improve the delineation of angioectasias, ulcers/erosions and villous edema/atrophy detected by SBCE, with almost perfect interobserver agreement for FICE 1.     

转化生长因子β1信号通路对胚胎肝前体细胞分化的诱导作用

目的探讨TGFβ1对胚胎肝前体细胞(HPC)分化的影响。方法体外培养HPC-E14. 5细胞株并以细胞免疫荧光染色法鉴定。将细胞分为对照组(HPC)、HPC+TGFβ1组和HPC+SB431542组。HPC+TGFβ1组滴加外源性TGFβ1,HPC+SB431542组加入TGFβ1受体抑制剂SB431542,处理72 h后通过qRT-PCR法和Western Blot法分别检测AFP、Alb、细胞角蛋白19(CK19)mRNA及蛋白的表达情况;糖原染色法检测细胞分化后的功能。计量资料多组间比较采用单因素方差分析,进一步两两比较采用Dunnett's t检验。结果 qRT-PCR检测结果:对照组的AFP mRNA表达量高于其他两组(F=128. 937,P 0. 01),HPC+TGFβ1组的CK19 mRNA表达量高于其他两组(F=414. 467,P 0. 01),HPC+SB431542组的Alb mRNA表达量最高(F=794. 929,P 0. 01)。Western Blot法检测结果:对照组的AFP蛋白表达量高于其他两组(F=269. 000,P 0. 01),HPC+TGFβ1组的CK19蛋白表达量高于其他两组(F=93. 010,P 0. 01),HPC+SB431542组的Alb蛋白表达水平均较其他两组明显升高(F=1086. 000,P 0. 01)。糖原染色法结果:对照组的糖原染色表达阳性面积比例小于其他两组(F=79. 251,P 0. 05)。结论 TGFβ1信号诱导HPC向有功能的胆管细胞分化,而阻断TGFβ1信号通路后HPC具有向成熟肝细胞分化的趋势,分化后的胆管细胞和肝细胞具有正常的糖原储存和合成功能,这些细胞可能能够参与代谢活动。     

新疆包虫病“医防结合”模式的建立及初步应用实践

目的 建立包虫病“医防结合”创新诊疗新模式,并将此模式应用推广。方法 选取新疆5个县级包虫病定点医院作为试点县,初步实施“医防结合”创新诊疗新模式。以伊犁州察布查尔县为例,探讨此模式初步实施效果。评估指标包括包虫病病人登记管理率、免费包虫病药品使用率、病人规范治疗率、随访督促服药率,治疗后的患者疗效得到科学评估。结果 梳理伊犁州察布查尔县人民医院2016年6月至2019年12月的包虫病患者救治情况,手术后服药患者137人,其中治愈患者109人,治愈率达79.6%;无手术指征药物治疗患者59人,治愈率16.9%,有效率59.3%。失访患者10人,病人规范治疗率94.9%;随访督促服药率94.9%。结论 实践证明,包虫病“医防结合”诊疗新模式的建立,在一定程度上规范了包虫病患者服药诊疗流程,可将此模式推广至其他县级包虫病定点医院。