Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

直肠癌切除前后腹腔冲洗液脱落细胞学对比研究

目的研究直肠癌术中腹腔多次冲洗，对于降低患者腹腔内脱落癌细胞阳性率的临床意义。方法对63例直肠癌患者术中腹腔冲洗分6次进行，肿瘤切除前3次，切除后3次；将6次腹腔冲洗液行常规病理学涂片细胞学检查结果进行对比。结果肿瘤切除前，全组患者腹腔冲洗液脱落癌细胞均呈阳性表达。肿瘤切除后第1次腹腔冲洗液脱落癌细胞阳性40例，第2次阳性33例，第3次阳性13例。肿瘤切除后第1次冲洗液的脱落癌细胞阳性结果与切除后第2次冲洗液阳性结果比较，P〉0.05，差异无统计学意义；但第3次冲洗液的脱落癌细胞阳性结果与第2次比较，P〈0.01，差异有统计学意义。结论对直肠癌患者进行术中多次腹腔冲洗可降低腹腔内脱落癌细胞的阳性率。     

早期联用MEP和大剂量rhGH对严重烫伤大鼠肠源性感染的影响

目的探讨早期联用美罗培南(MEP)和大剂量重组人生长激素(rhGH)对严重烫伤免疫抑制大鼠肠源性感染的影响。方法Wistar大鼠54只随机分为对照组、烧伤组和治疗组(C1组、C2组、C3组),后两大组制成25%总体表面积(TBSA)Ⅲ°烫伤免疫抑制模型,伤后2h给予rhGH1.33IU/kg、MEP20mg/kg,伤后8、24h检测门静脉血清内毒素(LPS)、腔静脉血清肿瘤坏死因子-α(TNF-α)含量,肝功能变化和肠道细菌移位率。结果C3(MEP+rhGH治疗)组LPS和TNF-α含量均显著低于其他组(P<0.01),与对照组差异无统计学意义(P>0.05),C3组未发现肠道细菌移位且肝功能检测指标显著低于其他组(P<0.01),与对照组差异无统计学意义(P>0.05)。结论早期联用MEP和rhGH治疗严重烫伤免疫抑制大鼠能显著减轻或防止肠道细菌/内毒素移位,减少炎症介质释放,保护脏器功能。     

Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation

Background Gastrointestinal stromal tumours (GISTs) are thought to arise from the interstitial cells of Cajal (ICCs). ICCs form a network surrounding the myenteric plexus and between-muscle fibres of the muscularis propria of the tubular GI tract. The cell of origin of so-called extra-gastrointestinal stromal tumours (EGISTs) is not known.Aim and methods To study the diversity of gross presentation of GISTs and to critically assess the incidence of EGISTs and their relationship to mural GISTs, a total of 200 neoplasms with typical morphologic and immunohistochemical features of GISTs were reviewed, looking for any degree of association with the muscularis propria of the gut wall.Results There were 130 gastric (65%), 9 duodenal (4.5%), 48 small intestinal (24%), 9 colorectal (4.5%), 1 appendiceal (0.5%) and 3 unclassifiable GISTs (1.5%). Fourteen cases (7%) were initially submitted as EGISTs (four mesenteric, four omental, one pararectal/prostatic, one pelvic/Douglas, one perivesical, one located between root of mesentery and tail of pancreas, one involving the mesentery, omentum and abdominal wall extensively and one located between liver and stomach). After critical re-evaluation of surgical reports and remote clinical history and a careful search for residual muscular tissue from the gut wall in the tumour pseudocapsule (in some cases supported by desmin immunoreactivity), it was possible to reclassify most of these cases (11/14) as either GISTs with extensive extramural growth resulting in loss of contact to the external muscle coat of the gut (8/14) or as metastases from an inoperable GIST (2/14) or from a previously resected deceptively benign tumour (1/14).Conclusion EGISTs are probably rarer than previously reported (1.5% or less in this study). We concluded that most so-called EGISTs represent apparent EGISTs that should have arisen from the outermost muscle coat, but have lost their contact to the point of origin due to extensive extramural growth pattern. From a surgical point of view, it is crucial to document and mark any focal attachment or adhesions to the gut wall noticed during surgery for an apparent EGIST. In contrast to most other neoplasms, GISTs should be defined by virtue of any degree of association with the muscularis propria (no matter how minimal), but not by localisation of the bulk of the tumour.     

MBP对PBMC产生IFN-γ和NO的影响

目的探讨T细胞非特异性活化在CNS脱髓鞘性疾病中的作用。方法分离实验性自身免疫性脑脊髓炎(EAE)易感性BALB/c小鼠外周血单个核细胞(PBMC),采用体外细胞培养方法在体外与碱性髓鞘蛋白(MBP)共培养,测定培养上清液中IFN-γ、NO水平。结果经MBP刺激的PBMC产生IFN-γ[(43.83±6.06)pg/mL]和NO[(180.76±20.75)μmol/L]明显增加,与对照组产生的IFN-γ[(28.52±2.18)pg/mL]和NO[(95.61±13.09)μmol/L]相比差异有统计学意义(P<0.01)。结论在CNS脱髓鞘性疾病发病过程中,活化的T细胞、单核细胞等分泌致炎细胞因子和其他有害物质增多。     

人精子体外氧化损伤对线粒体tRNA~(LeuUUR)基因的影响

目的:探讨活性氧(ROS)对人类精子线粒体tRNALeuUUR基因的氧化损伤。方法:采用Percoll梯度离心法筛选具有正常生理功能的精子,作为正常精子模型,并分为损伤组20例和对照组20例,分别加入次黄嘌呤-黄嘌呤氧化酶体系或不予处理,37℃有氧环境中孵育60min。分别提取精子DNA,以Fpg酶切损伤碱基并采用接头介导PCR(LM-PCR)检测线粒体tRNALeuUUR基因的氧化损伤。采用Rhodamine(Rh123)荧光探针标记精子,通过流式细胞仪检测线粒体膜电位,观察精子的功能。结果:与对照组相比,损伤组精子孵育后线粒体膜电位明显降低[(116.27±11.72)%vs(64.00±4.88)%,P<0.05]。Fpg酶切和LM-PCR显示精子线粒体tRNALeuUUR基因损伤。结论:ROS可能通过对精子线粒体tRNALeuUUR基因氧化损伤而影响精子功能(线粒体膜电位明显降低),从而引起不育。     

Renal fibrosis and the origin of the renal fibroblast.

Many studies have determined that the extent of tubulointerstitialinvolvement, particularly fibrosis, correlates better with renalfunction than glomerular changes do, thus, the extent of tubulointerstitialdamage in any given renal biopsy has important implicationsfor the renal prognosis of the patient (summarized in [1]).Tubulointerstitial fibrosis is characterized by the accumulationof extracellular matrix components including collagen typesI, III, IV, proteoglycans and fibronectin. In recent years,much controversy has been created in the nephrology communityregarding the origin of matrix-producing cells in the kidney.Several possibilities exist, including activation of residentinterstitial fibroblasts, migrating haematopoietic or mesenchymalstem cells from the bone marrow, periadventitial cells and epithelial–mesenchymaltransition (EMT) of tubular epithelial cells. This review summarizesrecent data indicating the possible origin of matrix-producingcells in the kidney, and illustrates from a clinical point of     

制作角膜缘干细胞完全缺乏动物模型的新方法

目的提出一种新的角膜缘干细胞完全缺乏模型制作方法,为干细胞缺乏疾病的治疗性研究提供可靠的模型。方法利用9mm环钻划界,板层切除角膜组织,通过临床评分、印迹细胞学、组织病理及免疫组织化学验证模型的成功。结果板层切除术后30~45d,模型眼角膜混浊、上皮缺损、大量新生血管长入,印迹细胞学可见PAS( )的杯状细胞,组织病理学检查上皮符合结膜细胞表型,免疫荧光染色可见结膜杯状细胞特异性标志MUC5AC阳性表达。结论环钻划界加板层切除法为一种可靠、有效的角膜缘干细胞完全缺乏模型制作方法。     

Wild Edible Plants and Their Traditional Use in the Human Nutrition in Bosnia-Herzegovina

This article presents first systematical procedure results on traditional usage of wild, edible, vitaminous, and aromatic plants in the nutrition of human population in Bosnia and Herzegovina (W. Balkan peninsula; SE Europe). By method of an ethnobotanical interview, which comprised of over 250 persons, whose average age was 55, and by research on edible wild flora all around Bosnia and Herzegovina that extended over many years, detected were 308 plants belonging to 73 plant families that are being used in nutrition and diet of indigenous population. Edible wild plants are used as delicious vegetables, fruits, peer and spices, in either fresh, raw, or dried condition. Plants are being used for the making of cooked food (33%), fresh salads (19%), mush and bread (17%), or as fresh, wild fruits and drinks (13%) or as spices and ethno-pharmacological potions (10%). The majority of identified, wild edible plants may satisfy the daily human need for elementary nutrition material, particularly those of vitamins C and A, and for some minerals, according to the regulations of World Health Organization (WHO).