Digital transplantation pathology: combining whole slide imaging, multiplex staining and automated image analysis

Conventional histopathology is the gold standard for allograft monitoring, but its value proposition is increasingly questioned. "-Omics" analysis of tissues, peripheral blood and fluids and targeted serologic studies provide mechanistic insights into allograft injury not currently provided by conventional histology. Microscopic biopsy analysis, however, provides valuable and unique information: (a) spatial-temporal relationships; (b) rare events/cells; (c) complex structural context; and (d) integration into a "systems" model. Nevertheless, except for immunostaining, no transformative advancements have "modernized" routine microscopy in over 100 years. Pathologists now team with hardware and software engineers to exploit remarkable developments in digital imaging, nanoparticle multiplex staining, and computational image analysis software to bridge the traditional histology-global "-omic" analyses gap. Included are side-by-side comparisons, objective biopsy finding quantification, multiplexing, automated image analysis, and electronic data and resource sharing. Current utilization for teaching, quality assurance, conferencing, consultations, research and clinical trials is evolving toward implementation for low-volume, high-complexity clinical services like transplantation pathology. Cost, complexities of implementation, fluid/evolving standards, and unsettled medical/legal and regulatory issues remain as challenges. Regardless, challenges will be overcome and these technologies will enable transplant pathologists to increase information extraction from tissue specimens and contribute to cross-platform biomarker discovery for improved outcomes.     

Cell–cell interaction between vocal fold fibroblasts and bone marrow mesenchymal stromal cells in three‐dimensional hyaluronan hydrogel

Mesenchymal stromal cells (MSCs) are multipotential adult cells present in all tissues. Paracrine effects and differentiating ability make MSCs an ideal cell source for tissue regeneration. However, little is known about how interactions between implanted MSCs and native cells influence cellular growth, proliferation, and behaviour. By using an in vitro three‐dimensional (3D) co‐culture assay of normal or scarred human vocal fold fibroblasts (VFFs) and bone marrow‐derived MSCs (BM‐MSCs) in a uniquely suited hyaluronan hydrogel (HyStem–VF), we investigated cell morphology, survival rate, proliferation and protein and gene expression of VFFs and BM‐MSCs. BM‐MSCs inhibited cell proliferation of both normal and scarred VFFs without changes in VFF morphology or viability. BM‐MSCs demonstrated decreased proliferation and survival rate after 7 days of co‐culture with VFFs. Interactions between BM‐MSCs and VFFs led to a significant increase in protein secretion of collagen I and hepatocyte growth factor (HGF) and a decrease of vascular endothelial growth factor (VEGF), monocyte chemotactic protein‐1 (MCP‐1) and interleukin‐6 (IL‐6). In particular, BM‐MSCs significantly upregulated matrix metalloproteinase 1 (MMP1) and HGF gene expression for scarred VFFs compared to normal VFFs, indicating the potential for increases in extracellular matrix remodelling and tissue regeneration. Application of BM‐MSCs‐hydrogels may play a significant role in tissue regeneration, providing a therapeutic approach for vocal fold scarring. Copyright © 2013 John Wiley & Sons, Ltd.     

三维能量多普勒对前列腺癌分化程度研究

目的 探讨三维能量多普勒在诊断前列腺癌及其分化程度方面的临床价值.方法 回顾性分析经直肠三维能量多普勒检查68个前列腺肿块血流特征,并与病理结果对照分析.结果 前列腺良恶性肿块的血管指数（VI）差异有统计学意义（t=4.654,P=0.000）.以VI＞0.21条/cm^3诊断前列腺癌的灵敏度77.8%、特异度65.2%.高、中、低分化组的前列腺癌肿血管指数分别为0.0975±0.0680、0.1811±0.0977、0.2588±0.0577,组间差异有显著性（P＜0.000）.结论 经直肠三维能量多普勒检查为前列腺癌诊断提供了新的途径和方法,并能协助诊断前列腺癌的分化程度.     

微小种植体支抗的三维有限元分析

目的 利用三维有限元进行微小种植体应力分析,寻找最适合正畸临床使用的微小种植体。方法 利用ANSYS软件建立10mm×20mm×30mm的颌骨骨块三维有限元模型;同时建立的长度为7mm、9mm、11mm,螺纹顶角为30°、60°、90°的9种圆柱状有螺纹微小种植体三维有限元模型;模拟微小种植体植入颌骨内并建立植入后模型,对微小种植体骨界面进行应力分析。结果 经ANSYS软件对微小种植体骨界面的应力分析,在不同角度的微小种植体中,螺纹顶角为60°的微小种植体三维有限元模型周边最大应力值最小,最适于临床使用。不同长度的微小种植体中,长度为7mm的微小种植体三维有限元模型周边最大应力值明显大于其他两种,不适用于正畸临床。9mm和11mm微小种植体三维有限元模型周边最大应力值差别不大,11mm微小种植体三维有限元模型周边最大应力值略小于9mm微小种植体三维有限元模型周边最大应力值。结论 螺纹顶角为60°,9mm以上的微小种植体适于正畸临床做为支抗使用。     

食管癌三维适形放射治疗靶区探讨

食管癌由于其自身生物学特点使其就诊时多为中晚期,因此,放射治疗是中晚期食管癌的主要治疗方式。而三维适形放射治疗(3DCRT)能够提高靶区的适形度,减少靶区周围正常器官和组织的照射剂量,并保护周围正常组织,并为食管癌治疗提供了新的研究方向。本研究通过对食管癌淋巴结转移模式和临床失败模式来分析食管的CTV范围。     

Ⅲ期非小细胞肺癌同步放化疗加诱导化疗的临床探讨

目的：通过观察期非小细胞肺癌同步放化疗加与不加诱导化疗疾病的进展情况与治疗的毒性反应,从而明确诱导化疗的意义。方法：将92例符合条件的期非小细胞肺癌患者随机分为两组。单纯同步放化疗组（对照组）和同步放化疗加诱导化疗组（实验组）,放疗采用三维适形技术,针对肺部原发灶及纵隔内≥1 cm的淋巴结,常规分割每次2 Gy,总剂量给予60～66 Gy,锁骨上有淋巴结转移者采用6MV-X线加电子线常规分割放疗至总量DT：60～66 Gy。化疗全部采用NP方案,对照组化疗2周期,实验组共化疗4周期。结果：92例患者全部完成治疗计划。两组的有效率分别为73.9%,78.2%。1,2,3年总生存率对照组为71.7%,41.3%,28.3%,中位生存期为11个月;实验组为73.9%,45.6%,30.4%,中位生存期为12个月。1,2,3年局部无进展生存率与中位无复发生存期对照组为60.9%,32.6%,17.4%和9个月;实验组为67.3%,36.9%,23.9%和11个月。实验组的毒副作用明显高于对照组。结论：同步放化疗加诱导化疗未能明显提高期非小细胞肺癌的生存率且毒性增加。     

缺血性心肌病与扩张型心肌病的超声心动图特征比较与鉴别诊断

 目的 探讨超声心动图对缺血性心肌病(ischemic cardiomyopathy,ICM)及扩张型心肌病(dilated cardiomyopathy,DCM) 的鉴别诊断价值。方法 收集175例因心功能不全、射血分数低且超声提示心脏扩张的患者,在纠正心衰后行选择性冠状动脉造影(selective coronary angiography,CAG),明确诊断为ICM或DCM,结果ICM组94例,DCM组81例,应用超声心动图分别对2组从心脏形态学、血流动力学及房室功能等方面进行比较。结果 ICM 组与 DCM 组多项超声指标间差异均有统计学意义(P<0.05或P<0.01)。相对于ICM ,DCM组患者心脏射血分数更低,DCM组的左房内径,右室内径,左室舒张末内径均大于ICM组,同时,DCM组的左室缩末容积及左室舒末容积均大于ICM组,同时,前者的主动脉瓣,肺动脉瓣口血流速度均小于后者。结论 ICM与DCM的心脏结构在超声的显示上有明显不同,前者心脏腔室内径相对较大,且主动脉瓣及肺动脉瓣口血流速度小于后者。     

Trait and state biomarkers for psychiatric disorders: Importance of infrastructure to bridge the gap between basic and clinical research and industry

To further improve clinical activities in psychiatry by early diagnosis and early intervention with novel mechanism‐guided treatments, there is a great need for biomarkers that reflect ‘trait’ and ‘state’ in major mental disorders. Stable trait biomarkers would allow early diagnosis, prognosis, and hopefully early intervention in these disorders, while dynamic state markers that reflect symptomatic changes would help to develop treatments that target these molecular mechanisms. However, in the search for such biomarkers, and eventually translating them to the clinic and industry, challenges currently exist at multiple levels, from basic scientific understanding, patient sample collection, and sample and data management, to bridging the gap between basic and clinical research and industry. To address these challenges, we propose an infrastructure that emphasizes: (i) a research and educational framework to facilitate translation between basic neuroscience, clinical research, and industry; (ii) patient recruitment and collection of disease‐relevant samples to study trait and state biomarkers; and (iii) a comprehensive database to integrate patient and sample information with biological and clinical data. We believe that such an approach would bolster: research into the biological mechanisms of psychiatric disorders; and collaboration among the laboratory, clinic, and industry to translate these findings into successful treatments.