The hepatic extracellular matrix

The unique nature of the hepatic extracellular matrix (ECM) is predicted by the special configuration of the space of Disse. Whereas other epithelial organs have two basement membranes (BM) and a substantial ECM interposed between endothelial and epithelial cells, the liver lobule has no BM and only an attenuated ECM, consisting mostly of fibronectin (FN), some collagen type I, and minor quantities of types III, IV, V, and VI. This configuration, together with the abundant fenestrations and gaps of the sinusoidal endothelial cells, seems ideally suited to facilitate the rapid bidirectional exchange of macromolecules normally taking place between plasma and hepatocytes. During organogenesis, the liver anlage is vascularized by continuous capillaries with BM, but by day 13.5 of development (in the rat) the vessels in the immediate proximity of hepatocytes become fenestrated, lacking specialized junctions and BM, suggesting that the hepatocytes produce signals capable of modulating the endothelial phenotype. In regeneration, hepatocyte proliferation precedes vascular proliferation resulting in the formation of hepatocyte clusters that, temporarily, lack sinusoids. Eventually, vascular proliferation follows and the normal hepatocyte-vascular relationships are restored. During this period laminin synthesis by Ito cells is prominent. As soon as hepatocytes become stable, secretion of the sinusoid phenotype-maintaining factors resumes and laminin synthesis and secretion terminates. The interplay between extracellular matrix and liver cells is essential for normal homeostasis and its modification results in derranged hepatic function.Parts of this editorial have been adapted from: A. Martinez-Hernandez, P.S. Amenta. Morphology, localization and origin of the hepatic extracellular matrix. In: Zern MA, Reid L (eds) Extracellular matrix: chemistry, biology, and pathology with emphasis on the liver. Marcel Dekker, New York, (in press)     

Plasminogen modulation of IL-1-stimulated degradation in bovine and human articular cartilage explants. The role of the endogenous inhibitors: PAI-1,α 2-antiplasmin,α 1-PI,α 2-macroglobulin and TIMP

The studies described here examine the involvement of the fibrinolytic cascade and its endogenous inhibitors in the regulation of activity of matrix metalloproteinases and cartilage degradation related to non-inflammatory joint disease, like osteoarthritis. An interleukin-1-induced model of degradation using [³⁵S]-labeled bovine and human articular cartilage explants was utilized. One goal of these studies was to compare the responses of bovine and human articular cartilage. Degradation was not inhibited by ₁-PI, PAI-1, ₂-macroglobulin, ₂-antiplasmin or TIMP-2, when IL-1 alone was added. Addition of human plasminogen to bovine explants, at concentrations found in human synovial fluid, increased degradation by three to fourfold. Under these conditions, the degradation was inhibited effectively by all of the endogenous inhibitors tested, indicating the presence of a cascade where activated chondrocytes are a source of u-PA. Plasminogen activated by u-PA gives plasmin, which is known to further activate pro-stromelysin. Stromelysin is essential for activation of collegenase. Not only TIMP, but also inhibitors at earlier steps of activation like PAI-1, ₂-antiplasmin, ₁-PI and ₂-macroglobulin inhibited degradation, and could provide cartilage protection in vivo. An experiment with human articular cartilage explants showed that very little or no degradation occurred when human articular cartilage explants were stimulated with interleukin-1 alone. Addition of human plasminogen (at physiologically relevant concentrations) resulted in significant degradation, which was inhibited in the same manner as in bovine explants, by inhibitors of the fibrinolytic cascade and TIMP. TIMP is much more efficient in human explants, indicating the limited participation of human plasmin in the degradation of human cartilage. Although speculative, it is possible that in vivo, cartilage degradation could be promoted not only by TIMP/MMP imbalance, but also accelerated by decreased levels of certain serpins in synovial fluid (e.g. PAIs, ₂-antiplasmin and ₁-PI).accepted by W. B. van den BergWork supported by OsteoArthritis Science Inc., One Kendall Square, Bldg. 200, Cambridge, MA 01139, USA.     

基于波士顿矩阵的医疗纠纷管理研究

目的针对医疗纠纷赔款案件的危害性进行风险分类分析,为提升科室医疗安全管理水平提供参考。方法分析某院2016年-2019年125例医疗纠纷赔款案件,借鉴波士顿矩阵模型,将医疗纠纷发生科室及原因围绕损害性（均次损害量化值）、损失性［每床位（均次）赔款金额］、发生频次3个指标进行风险分类。结果医疗纠纷赔款案件高发科室主要是骨科（33.6%）和普外科（23.2%）,发生原因主要是责任心不强（22.4%）、手术不当（20.8%）、漏诊误诊（16.8%）。“高床位赔款,高损害风险”科室有心外科及普外科,“高床位赔款,低损害风险”科室有泌尿外科、骨科及神经外科;“高赔款,高损害风险”医疗纠纷原因有漏诊误诊、用药不合理、医疗并发症、手术不当,“低赔款,高损害风险”医疗纠纷原因有院内感染、责任心不强。结论波士顿矩阵模型能够为医疗纠纷防范提供风险评估工具,从而助力科室安全管理。管理者可结合风险评估结果,采取差异化管理策略。     

公立医院优势学科病种绩效管理研究:以骨科为例

目的从循证视角建立公立医院优势学科病种绩效管理工具。方法以波士顿矩阵理论为指导,以“病种均次毛利率、病种均次住院日”为主要指标,“日均毛利率”为辅助指标,采用Microsoft office EXCEL 365 软件进行分析。结果2019年骨科平均住院日为4.99 d,均次平均毛利率为23.62%,日均毛利率平均值为4.73%。骨科200例以上病种、不同亚专科病区病种、同一亚专科病区内不同病种、不同亚专科病区相同病种,绩效均存在差异。结论 管理者应对不同病种绩效指标进行适当校正,探索精细化病种诊疗与管理模式。     

肌动蛋白是大鼠肝细胞核基质的组分之一

目的：证实肌动蛋白存在于大鼠肝细胞核基质中。方法：应用SDS－PAGE法分析大鼠肝细胞核基质的组分,以肌动蛋白多克隆抗体进行Westem Blot免疫印迹检测。结果：核基质蛋白SDS－PAGE图谱中可见相当于肌动蛋白的43KD条带,Westem Blot分析证实核基质中存在肌动 蛋白条带。结论：肌动蛋白是大鼠肝细胞核基质的组分之一。     

5-氨基水杨酸缓释骨架片的研制

目的 :制备 5_氨基水杨酸缓释骨架片。方法 :采用羟丙基甲基纤维素作为骨架材料 ,湿法制粒压片制备 ,并考察体外释药情况。结果 :5_氨基水杨酸缓释骨架片体外释药符合Higuchi方程。结论 :5_氨基水杨酸缓释骨架片具有显著的缓释效果。     

Selected conditions associated with an increased incidence of incisional hernia: A review of molecular biology

BackgroundIncisional hernias (IH) following a laparotomy, on average, occur in 10–20% of patients, however, little is known about its molecular basis. Thus, a better understanding of the molecular mechanisms could lead to the identification of key target(s) to intervene pre-and post-operatively.MethodsWe examined the current literature describing the molecular mechanisms of IH and overlap these factors with smoking, abdominal aortic aneurysm, obesity, diabetes mellitus, and diverticulitis.ResultsThe expression levels of collagen I and III, matrix metalloproteinases, and tissue inhibitors of metalloproteases are abnormal in the extracellular matrix (ECM) of IH patients and ECM disorganization has an overlap with these comorbid conditions.ConclusionUnderstanding the pathophysiology of IH development and associated risk factors will allow physicians to identify patients that may be at increased risk for IH and to possibly act preemptively to decrease the incidence of IH.     

基质金属蛋白酶类水平与抗结核药物性导致肝损伤的相关性分析CSCD

目的:分析抗结核药物导致的肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)患者基质金属蛋白酶类(matrix metalloproteinases,MMP)水平及其相关性。方法:采用回顾性研究方法,收集2019年6月至2020年6月昆明市第三人民医院收治的肺结核患者中发生ATB-DILI的98例患者作为病例组;选取同期门诊健康体检者30名作为对照组。采集研究对象晨起空腹静脉血6 ml,采用双抗体夹心法检测其MMP-1、MMP-2、MMP-7、MMP-9、MMP-13、MMP-14浓度。病例组研究对象根据ATB-DILI临床分型分为肝细胞损伤型(A组)、胆汁淤积型(B组)、肝血管损伤型(C组)、混合型(D组);根据ATB-DILI严重程度分为0级(无肝损伤)、1级(轻度肝损伤)、2级(中度肝损伤)、3级(重度肝损伤)、4级(急性肝功能衰竭)、5级(致命)。比较不同临床分型组及对照组研究对象MMP水平;分析MMP水平与ATB-DILI严重程度分级相关性。结果:按照ATB-DILI临床分型,病例组中A组有51例,B组有12例,C组有15例,D组有20例;根据ATB-DILI严重程度分级,病例组中1级有33例,2级有27例,3级有22例,4级有14例,5级有2例。A、B、C、D组及对照组MMP-1浓度分别为:(89.1±11.2)ng/ml、(32.3±6.3)ng/ml、(47.5±9.1)ng/ml、(55.2±11.1)ng/ml、(27.5±8.2)ng/ml;MMP-2浓度分别为:(8.2±2.1)ng/ml、(6.2±2.3)ng/ml、(15.5±1.8)ng/ml、(7.2±1.6)ng/ml、(3.2±1.3)ng/ml;MMP-9浓度分别为:36.1(25.9,47.3)ng/ml、11.3(5.1,20.6)ng/ml、14.1(6.1,21.3)ng/ml、15.3(3.8,28.1)ng/ml、6.4(2.8,8.6)ng/ml;MMP-14浓度分别为:5.2(2.8,7.5)ng/ml、6.0(3.6,8.9)ng/ml、11.2(5.2,17.4)ng/ml、4.0(1.8,6.2)ng/ml、2.8(1.4,4.3)ng/ml。A组MMP-1和MMP-9浓度明显升高,C组MMP-2和MMP-14浓度明显升高,差异均有统计学意义(F=7.983,P=0.031;H=9.979,P=0.041;F=9.381,P=0.010;H=10.555,P=0.032)。ATB-DILI严重程度1、2、3、4、5级患者MMP-9浓度分别为:16.2(13.2,19.3)ng/ml、21.5(18.4,23.6)ng/ml、24.3(20.6,27.1)ng/ml、30.3(25.1,35.3)ng/ml、38.5(33.9,43.1)ng/ml,与严重程度分级呈正相关(r=0.882,P=0.000)。结论:不同临床分型ATB-DILI患者MMP-1、MMP-2、MMP-9、MMP-14浓度有不同程度升高;MMP-9浓度与ATB-DILI严重程度呈正相关;MMP水平可能为ATB-DILI发生的影响因素。     

Periventricular- intraventricular hemorrhage in the premature infant- A historical perspective

The objective of this chapter is to trace the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow changes in the genesis of hemorrhage, clinical factors that increase the bleeding risk, and potential preventative strategies. In 1976, neuropathological studies demonstrated capillary rupture within the germinal matrix as the precursor of hemorrhage. In 1980, introduction of cranial ultrasound facilitated diagnosis of intraventricular hemorrhage. In 1979, loss of cerebral autoregulation in sick newborn infants was demonstrated. In the 1980’s, studies demonstrated the importance of intravascular factors in provoking hemorrhage. In 1983, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. In 1994, antenatal steroids use to accelerate lung development was recommended. This was associated with an unanticipated reduction in hemorrhage. In the mid 1990’s early indomethacin administration was associated with a reduction of severe hemorrhage.     

异搏定和三苯氧胺合并化疗治疗42例恶性肿瘤观察

目的：探索异搏定和三苯氧胺作为耐药调变剂与化疗联合应用治疗恶性肿瘤的作用。方法：对８２例恶性肿瘤患者进行随机分组对照实验,４２例化疗同时加用异搏定和三苯氧胺,４０例单纯化疗,两组化疗方案相同。结果：两组总有效率分别为６１．９％和４０．０％,治疗组与对照组疗效相比有显著性差异（Ｐ＜０．０５）,毒副作用两组无明显差别。结论：异搏定和三苯氧胺与化疗合用有助于改善化疗效果。