细胞凋亡及增殖细胞核抗原在肝癌组织中的表达及意义

目的探讨经肝动脉化疗栓塞(TACE)后肝癌细胞中增殖细胞核抗原(PCNA)广凋亡细胞比值与肝细胞肝癌分化程度的关系。方法应用原位末端标记法(TUNEL)及免疫组化双染色技术，对60例肝细胞肝癌石蜡包埋组织进行检测。结果不同分化程度癌组织中细胞凋亡和PCNA的阳性率不同。分化程度高，细胞凋亡阳性率高、PCNA阳性率偏低；分化程度低，细胞凋亡阳性率偏低、PCNA阳性率高。随分化程度的降低，PCNA广凋亡细胞的比值显著增加，两者有相关性。结论PCNA/凋亡细胞的比值可作为评估肝细胞肝癌分化程度的指标。     

Amplification and over‐expression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells

Gene amplifications in the 17q chromosomal region are observed frequently in breast cancers. An integrative bioinformatics analysis of this region nominated the MAP3K3 gene as a potential therapeutic target in breast cancer. This gene encodes mitogen‐activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which has not yet been reported to be associated with cancer‐causing genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast cancers. Knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation in MAP3K3‐amplified breast cancer cell lines MCF‐7 and MDA‐MB‐361 but not in MAP3K3 non‐amplified breast cancer cells. Knockdown of MAP3K3 expression in MAP3K3‐amplified breast cancer cells sensitized breast cancer cells to apoptotic induction by TNFα and TRAIL, as well as doxorubicin, VP‐16 and fluorouracil, three commonly used chemotherapeutic drugs for treating breast cancer. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized human breast epithelial cells (MCF‐10A). Combined, these results suggest that MAP3K3 contributes to breast carcinogenesis and may endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore, MAP3K3 may be a valuable therapeutic target in patients with MAP3K3‐amplified breast cancers, and blocking MAP3K3 kinase activity with a small molecule inhibitor may sensitize MAP3K3‐amplified breast cancer cells to chemotherapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Functional characterization of histamine H4 receptor on human mast cells

Among the four different types of histamine receptors (H1-H4), H4R is predominantly expressed in immune cells and involved in immunomodulatory response. Here, in this study we determined the expression of H4R in human mast cells (HMC-1, LAD-2 and primary cord blood derived CD34+ human mast cells) and characterized its functional properties. Interestingly, we found that human mast cells responded to both histamine (natural ligand) and 4-methylhistamine (selective H4R agonist) for sustained intracellular calcium mobilization, degranulation and cytokine production. However, only histamine induced the release of cAMP, but 4-methylhistamine down regulates cAMP indicating that H4R mediates its effect through Gαi/o protein and H1R via Gαq protein. Furthermore, both histamine and 4-methylhistamine induced the production of cysteinyl leukotrienes and LTB4. Using human inflammation antibody array membrane, we found that H4R induced the expression of various inflammatory proteins, involving pro-inflammatory cytokines and chemokines and these are TGF-β1, TNF-α, TNF-β, PDGF-BB, TIMP-2, M-CSF, IP-10, IL-16, IL-6, IL-3, IL-10, MIP-1α, IL-1α, ICAM-1, Eotaxin-2, RANTES, IL-8, MCP-1, and IL-6sR. We also quantified the level of various inflammatory cytokines produced by human mast cells through H4R. It was observed that, the production level of Th2 cytokines IL-4(401.34 pg/ml), IL-5 (64.21 pg/ml) and IL-13 (1044 pg/ml) and classical proinflammatory cytokines IL-6 (221.27 pg/ml) and IL-1β (34.24 pg/ml) and chemokines MCP-1(106 pg/ml) and IL-8 (818.32 pg/ml). Furthermore, activation of H4R caused the phosphorylation of ERK and PI3 K in a time dependent manner. Taken together these data demonstrate that, the activation of H4R in human mast cells produced not only inflammatory mediators that are associated with allergic reactions but also other inflammatory conditions.     

益肺增智汤配合针刺治疗血管性痴呆45例临床观察

目的观察益肺增智汤配合针刺治疗血管性痴呆（VD）的临床疗效。方法将90例血管性痴呆患者随机分为2组。治疗组45例采用益肺增智汤配合针刺治疗,对照组45例采用阿米三嗪萝巴新片（都可喜）30mg,每日2次口服,同时予胞二磷胆碱O．5g,每日1次静脉滴注。2组均30d为1个疗程,1个疗程后观察疗效,并应用简易智能量表（MMSE）、长谷川痴呆量表（HDS）、日常生活能力量表（ADL）及痰瘀闭阻型主要症状的积分变化进行检测评估,测定治疗前后血、尿常规及肝肾功能检查及毒副反应进行安全性考察。结果治疗组总有效率88．9％,对照组总有效率64．4％,2组比较差异有统计学意义（P〈0．05）。治疗组治疗后MMSE、HDS及ADL积分与本组治疗前比较差异均有统计学意义（P〈0．05）。2组治疗后MMSE、HDS及ADL差值积分比较差异均有统计学意义（P〈0．05）。2组中医证候疗效总有效率比较差异有统计学意义（P〈0．05）。结论益肺增智汤配合针刺治疗VD疗效显著。     

新辅助化疗对乳腺癌细胞凋亡和增殖的影响

背景与目的：在实验研究中,已证实多种化疗药物都可引起乳腺癌细胞的凋亡。但在人体内进行有关化疗药物引起乳腺癌细胞凋亡的研究,还少有报道。本文研究新辅助化疗能否引起乳腺癌肿瘤细胞的凋亡以及对乳腺癌肿瘤细胞增殖的影响。方法：应用末端转移酶介导的dUTP切口末端标记法（TdT-mediated dUTP nick end labelling,TUNEL)及免疫组化的标记链菌亲和素生物素法（Labelled Streptavidin Biotin,LSAB),分别检测100例乳腺癌组织中肿瘤细胞的凋亡指数（Apoptotic index,AI)和乳腺癌肿瘤组织的增殖细胞核抗原（Proliferating cell nuclear antigen,PCNA)表达。结果：新辅助化疗组肿瘤细胞凋亡指数（AI）均数为7．47％,与对照组肿瘤细胞凋亡指数（AI）均数4．83％相比明显增高（P＜0．01）。新辅助化疗组肿瘤细胞增殖细胞核抗原（proliferation cell nuclear antigen,PCNA)阳性表达率均数为33．71％,与对照组PCNA阳性率均数51．52％相比明显降低（P＜0．01）。在新辅助化疗组及对照组两组病例中,肿瘤细胞凋亡指数（AI）与增殖细胞核抗原（PCNA）的阳性表达均呈负相关。结论：在人体乳腺癌组织中,新辅助化疗能诱导肿瘤细胞发生凋亡,并能抑制其增殖。     

DF化疗、放疗序贯应用治疗食管癌疗效报道

 目的 食管癌化疗序贯放疗和单纯放疗疗效对比研究。方法 248 例食管癌随机分为综合治疗组125 例和单纯放疗组123 例。综合组：DDP（50mgm^{2>/sup> ,D1 ,8）5 FU（750mgm2>/sup> ,D2 6） 静脉注射,3 周为一周期,潘生丁50mg,口服,每天三次。2 3 周期化疗后放疗（DT60 70Gy6-5 7-5周）.单纯放疗组直接放疗（DT60 70Gy6-5 7-5 周）.结果 两组近期疗效无明显差别,综合组完全缓解率及1 ,3,5 年生存率高于单纯放疗组（p < 0-05）.结论 化疗后序贯放疗是治疗食管癌安全有效的方法。}     

Methylation of α‐Amino Acids and Derivatives Using Trimethylsilyldiazomethane

A study of the methylation of N‐nosyl‐α‐amino acids and derivatives with trimethylsilyldiazomethane is here reported. Trimethylsilyldiazomethane allows the chemo‐specific methylation of the carboxyl function of N‐nosyl‐α‐amino acids in high yields and purity. This method provides a practical route to N‐methyl‐α‐amino acids avoiding the use of the more toxic and explosive diazomethane. This simple and safe methylation methodology of α‐amino acids and derivatives is not limited to organic synthesis and involves the use of a commercially available reagent as well.     

Pre‐operative trans‐catheter arterial chemo‐embolization increases hepatic artery thrombosis after liver transplantation – a retrospective study

Little is known about nonsurgical risk factors for hepatic artery thrombosis (HAT ) after liver transplantation (LT ). We determined risk factors for HAT occurring within 90 days post‐LT and analysed the effect of HAT on graft and patient survival. Donor and recipient demographics, surgery‐related data and outcome in transplants complicated by thrombosis (HAT +) and their matched controls (HAT ?) were compared. Risk factors were assessed by univariate logistic regression. Median (IQR ) is given. A total of 25 HAT occurred among 1035 adult LT (1/1997–12/2014) and 50 controls were manually matched. Donor and recipient demographics were similar. Pre‐LT trans‐catheter arterial chemo‐embolization (TACE ) was more frequent in HAT + (HAT + 20% vs. HAT ? 4%, P = 0.037). HAT + had longer implantation [HAT + 88 min (76–108) vs. HAT ? 77 min (66–93), P = 0.028] and surgery times [HAT + 6.25 h (5.18–7.47) vs. HAT ? 5.25 h (4.33–6.5), P = 0.001]. Early graft dysfunction and sepsis were more frequent in HAT + and hospitalization longer. TACE had the greatest odds ratio in unadjusted analysis (OR : 6, 95% CI : 1.07–33.53, P = 0.03). All but seven grafts were lost after HAT (HAT + 72% vs. HAT ? 36%, P = 0.003); however, patient survival was unaffected (HAT + 79.8% vs. HAT ? 76%, P = 0.75). LT candidates undergoing TACE are at risk of developing HAT early after transplant.     

化疗药配制箱对机体保护作用的动物实验研究

目的 通过化疗药物配制箱在配药操作中对小白鼠影响的实验，以此研究对医护人员机体的保护作用。方法 随机将99只小白鼠分为A、B、C3组，每组30只。A组置于化疗药配制箱内，B组置于化疗药配制箱外，C组置于未配制化疗药箱内。观察3组小白鼠的外观行为，食欲，毛发，活动情况，白细胞，血小板，体质量的变化。结果 A组小白鼠活动灵敏度下降，食欲减少，毛发脱落，三项指标A组与B、C组比较t检验有显性差异，P＜0．001。B组、C组小白鼠活动自如，食欲正常，未见毛发脱落；三项指标两组比较无显性差异，P＞0．05。结论 化疗药配制箱临床应用可对医护人员的机体起到保护作用。