A technique for relative quantitation of cancer biomarkers in formalin‐fixed,paraffin‐embedded (FFPE) tissue using stable‐isotope‐label based mass spectrometry imaging (SILMSI)

We developed a novel technique for the relative quantitation of pairs of cancer biomarkers in formalin‐fixed paraffin‐embedded (FFPE) tissue. The method utilizes stable isotope labeled (SIL) chromogens deposited during the standard immunohistochemistry (IHC) tissue staining process. The labeled chromogens are precipitated on tissue enzymatically using the standard IHC protocols. The tissue is then imaged with matrix‐free laser desorption ionization time‐of‐flight mass spectrometry, and peak intensities of reporter ions are used to estimate the relative quantitation of protein biomarkers across the tissue. The relative abundance of two breast cancer biomarkers, estrogen receptor (ER) and progesterone receptor (PgR), were quantitated using their ratio of expression in xenograft models, and the ratios were found to be reproducible both within and across serial sections. The relative quantification of multiple biomarkers in situ across a single tissue section adds an additional dimension in cancer histological evaluation by allowing a visual and statistical assessment of tumor heterogeneity. Copyright © 2015 John Wiley & Sons, Ltd.     

A General Strategy for Targeting Drugs to Bone

Targeting drugs to their desired site of action can increase their safety and efficacy. Bisphosphonates are prototypical examples of drugs targeted to bone. However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Furthermore, bisphosphonate bone affinity comes at the expense of very low and variable oral bioavailability. FPPS inhibitors were developed with a monophosphonate as a bone‐affinity tag that confers moderate affinity to bone, which can furthermore be tuned to the desired level, and the relationship between structure and bone affinity was evaluated by using an NMR‐based bone‐binding assay. The concept of targeting drugs to bone with moderate affinity, while retaining oral bioavailability, has broad application to a variety of other bone‐targeted drugs.     

远端胃大部分切除术后消化道重建术式的对比研究

目的 对比远端胃大部分切除术后行连续性空肠间置术与BillrothⅠ式及Roux-en-Y 式吻合术的临床效果。方法 回顾性分析2012 年1 月至2013 年6 月接受手术的远端胃癌患者95 例,按不同消化道重建方式分为3 组。A 组30 例患者行连续性空肠间置术,B 组32 例行BillrothⅠ式吻合术,C 组33 例行Roux-en-Y 式吻合术。比较3 组患者术前预后营养指数（PNI）、手术时间、术后6个月及1 年并发症发生率、进食量、血浆白蛋白水平、体重及Visick 分级指数。结果 3 组患者术前PNI均无统计学差异（均P＞0.05）。A 组患者手术时间与B 组无明显差异,且均明显少于C 组的手术时间（均P＜0.05）。术后6 个月及术后1 年3 组患者的进食量、体重及营养状况的恢复均无统计学差异（均P＞0.05）。A 组患者术后腹胀情况明显少于C 组（P＜0.05）,胆汁反流性胃炎明显少于B 组（P＜0.05）。结论 胃大部分切除术后连续性空肠间置,安全有效,与传统的BillrothⅠ式及Roux-en-Y 式吻合术比较,可缩短手术时间,更快的恢复患者的消化功能,维持消化道正常通路,防止胆汁反流,将有可能成为消化道重建的主要方式之一。     

上皮细胞黏附分子在胃癌组织中的表达及其与预后的关系

目的 探讨上皮细胞黏附分子（EPCAM）在胃癌组织中的表达及其与胃癌浸润转移及预后的关系,以及EPCAM作为胃癌早期诊断、预后判断和治疗靶点的临床价值。方法 应用免疫组织化学法检测436 例胃癌组织及92例癌旁非肿瘤胃黏膜组织中EPCAM 的表达情况,分析并探讨EPCAM 的表达与临床病理参数及预后的关系。结果 在92 例非肿瘤胃黏膜组织中,50例（54.3%）EPCAM 蛋白为阴性表达,42例（45.7%）呈弱阳性表达。在436 例胃癌组织中,EPCAM 蛋白高表达179 例（41.1%）,低表达257 例（58.9%）,主要在细胞包膜表达。EPCAM 蛋白的表达强度与肿瘤部位、肿瘤大小、Lauren 分型、浸润深度、淋巴结分期、TNM 分期、淋巴结转移和远处转移密切相关（均P＜0.01）,而与患者性别、分化程度、组织学类型无关（均P ＞0.05）。EPCAM 高表达患者的5 年生存率（57.2%）明显低于EPCAM 低表达胃癌患者的5 年生存率（17.3%,P＜0.05）。I、II 和III 期EPCAM高表达胃癌患者的5年生存率明显低于EPCAM 低表达患者的5年生存率（P＜0.05）;IV 期EPCAM 高表达和低表达胃癌患者的5年生存率无统计学差异。EPCAM 表达、远处转移和TNM 分期（均P＜0.05）是胃癌的独立预后因素。结论 EPCAM 在胃癌中高表达,且其表达与淋巴结转移、远处转移、肿瘤的TNM 分期显著相关,提示EPCAM 可以作为胃癌的早期诊断的筛查指标以及治疗的靶点之一。     

血清CEA、CA19-9、CA72-4联合检测对胃癌诊断的价值

目的 探讨肿瘤标志物联合检测在胃癌诊断中的应用价值。方法 采用电化学发光分析法测定经病理检查证实的127 例各期胃癌患者和105 例胃良性病变及98 例健康体检者的血清CEA、CA19-9、CA72-4 水平并进行统计和分析,计算单项检测与联合检测诊断胃癌的灵敏度及特异度并作比较。结果 胃癌患者的CEA、CA19-9、CA72-4水平均明显高于胃良性病变患者及正常对照者, 差异均有统计学意义（均P＜0.05）;胃良性病变患者与正常对照者比较,差异无统计学意义（P＞0.05）。3 项指标联合检测诊断胃癌的灵敏度达87.4%,明显高于其他任一单项检测的灵敏度,差异有统计学意义（均P＜0.05）;3 项联合检测的特异度为52.7%,虽明显低于其他任一单项检测的特异度,但差异无统计学意义（均P＞0.05）。胃癌术后复发者CEA、CA19-9、CA72-4 的水平明显高于未复发者,差异有统计学意义（均P＜0.01）。结论 血清多项肿瘤标记物联合检测有助于提高胃癌诊断的阳性率。     

Managing of Procambarus clarkii by X-ray sterilisation of males: Cytological damage to gonads

Procambarus clarkii is an invasive alien species spreading worldwide. It is therefore mandatory to find new methods to manage this species since traditional techniques are not sufficient for this purpose. The present study investigates gonad damage induced by different doses of ionising irradiation: 20, 40 and 60 Gy. Testis were analysed after 10 and 30 days by means of light, scanning and transmission electron microscopy. Control unirradiated testes present an acinar structure with a well-defined germinative cells maturation from the distal proliferative zone to the proximal stalk of the lobes whilst, in irradiated testes, induced apoptosis of germinative and accessory cells and a high level of vacuolisation inside the acini were identified, progressively increasing in accordance to Gy dosage and time after exposure. We determined the dose of 40 Gy as the best compromise: it causes an extensive damage to germinative tissues without affecting crayfish vitality, differing from 60 Gy. From an applicative point of view, this dose reduces the efforts, in terms of cost and time, for the application of SMRT.     

Composite PLA/PEG/nHA/Dexamethasone Scaffold Prepared by 3D Printing for Bone Regeneration

3D printing has become an essential part of bone tissue engineering and attracts great attention for the fabrication of bioactive scaffolds. Combining this rapid manufacturing technique with chemical precipitation, biodegradable 3D scaffold composed of polymer matrix (polylactic acid and polyethylene glycol), ceramics (nano hydroxyapatite), and drugs (dexamethasone (Dex)) is prepared. Results of water contact angle, differential scanning calorimeter, and mechanical tests confirm that incorporation of Dex leads to significantly improved wettability, higher crystallinity degree, and tunable degradation rates. In vitro experiment with mouse MC3T3‐E1 cells implies that Dex released from scaffolds is not beneficial for early cell proliferation, but it improves late alkaline phosphatase secretion and mineralization significantly. Anti‐inflammation assay of murine RAW 264.7 cells proves that Dex released from all the scaffolds successfully suppresses lipopolysaccharide induced interleukin‐6 and inducible nitric oxide synthase secretion by M1 macrophages. Further in vivo experiment on rat calvarial defects indicates that scaffolds containing Dex promote osteoinduction and osteogenic response and would be promising candidates for clinical applications.     

Imaging through flesh tissue using fs electronic holographic gating method

The experimental results of imaging through flesh tissue using fs electronic holographic gating method is reported. In the experiment, Ti: sapphire mode-locked laser is used as light source, of which the repetition rate is 100 MHz, central wavelength 800 nm, duration of pulse 20 fs, output power 80 mW. Tissue is a 7 mm thick chicken slice, and the imaged object is a metal wire with diameter of 0.5 mm. A general CCD is used to record holograms and a clear image of metal wire is obtained. Several relevant problems are discussed.