细胞外基质蛋白1在原发性肝癌中的表达与预后的关系

目的 探讨原发性肝癌中细胞外基质蛋白1(extracellular matrix protein 1,ECM1)表达水平与肝癌预后的关系.方法 选取77例原发性肝癌手术切除标本,采用免疫组织化学方法检测ECM1表达,并分析ECM1表达与肝癌临床病理特征及预后与复发的关系.结果 免疫组织化学染色显示ECM1主要表达在胞质中.肝癌组织中ECM1表达阳性率为74.0%(57/77),与肝癌血管侵犯(χ2=6.523,P=0.011)和TNM分级有关(χ2=6.989,P=0.030),而与患者性别、年龄、血清AFP水平、肿瘤大小、癌灶数、分化程度等指标无明显相关性(P＞0.05).ECM1阳性表达患者术后总生存率和无瘤生存率明显低于阴性表达者(P=0.016).多因素分析表明,ECM1表达是影响肝癌总生存和无瘤生存的独立危险因素(RR=3.721,P=0.002;PR=2.323,P=0.031).结论 EC M1的表达与肝癌侵袭转移特性有关,可作为判断肝癌术后预后、复发的指标之一.

Abstract：

Objective To examine the expression of extracellular matrix protein 1 ( ECM1 ) in hepatocellular carcinoma (HCC) and its correlation with prognosis and recurrence of HCC.Methods Immunohistochemistry was used to detect expression of ECM1 in cancerous tissues from 77 HCC patients. The correlation between ECM1 expression and clinicopathologic features and prognosis were analyzed. Results ECM1 is mainly expressed in the cytoplasm of liver cells. The positive rate of ECM1 expression in HCC tissues were 74. 0% (57/77), and the expression level was significantly correlated with vascular invasion (χ2 =6.523, P =0.011 ) and TNM stage (χ2 =6.989, P =0.030). No significant correlation was found between the expression of ECM1 and patient's gender, age, AFP level of plasm, tumor size, number of nodules, and tumor differentiation. Patients with positive ECM1 expression have significantly poorer overall survival (OS) and disease-free survival (DFS) after curative resection than those with negative ECM1 expression (P =0. 016). The Cox multivariate analysis demonstrated that among the factors analyzed, ECM1 expression is an independent prognostic factors for OS and DFS in HCC patients after a curative resection (RR=3.721, P=0.002; RR=2.323, P=0.031). Conclusions Positive ECM1 is correlated with postoperative metastasis and invasion of HCC and poor prognosis.     

骨髓移植诱导临床心脏移植后供者特异性免疫耐受方案的探讨

目的 探讨骨髓移植诱导临床心脏移植后供者特异性免疫耐受的可行性.方法 采取供心的同时采用改良"灌流法"获取供者的骨髓350 ml,经过滤及离心处理后,加入细胞冷冻保护液共80ml,分装于低温冻存袋,经程序降温,置于-80℃冰箱中保存.在常规原位心脏移植术后40 d,取冻存骨髓快速复温,穿刺受者双侧髂后上嵴,立即行骨髓腔内骨髓细胞输注(IBM-BMT),共输注单核细胞1.2×107/kg,CD34+细胞2.38×105/kg.骨髓输注前3 d行预处理,包括应用氟达拉滨、抗胸腺细胞球蛋白及全身淋巴结照射.骨髓移植后静脉应用他克莫司(Tac),维持血Tac浓度谷值在10～20μg/L;3周后改为口服Tac+吗替麦考酚酯(MMF);6周后改为环孢素A及MMF.分别于心脏移植后2、4、8和12周采集受者外周血,分别于术后4、8和12周采集受者的骨髓,应用短串联重复序列-聚合酶链反应法检测供者嵌合体.心脏移植后每周行心肌内心电图检查,每月行心肌活检1次.术后3个月,取受者及第三者外周血单核细胞,行混合淋巴细胞反应(MLR).结果心脏移植后1、2及3个月时受者的外周血及髂骨内骨髓细胞中供者来源的细胞比例分别为26.3%、19.1%、4.8%和46.3%、24.4%、7.6%.IBM-BMT后心肌内心电图监测显示心肌阻抗及R波波幅无明显变化.术后3个月行心内膜心肌活检,未见排斥反应征象.术后3个月时行超声心动图检查,提示心脏舒张、收缩功能良好.MLR提示受者对供者特异性刺激呈现低反应性,而对第三者仍保持良好的免疫活性(P＜0.01).结论 采取分期骨髓移植免疫耐受诱导方案可安全、有效地建立嵌合体,成功诱导心脏移植后供者特异性免疫耐受,但远期效果有待进一步研究.

Abstract：

Objective To investigate a new strategy of bone marrow transplantation (BMT) for donor-specific tolerance induction after heart transplantation. Methods Donor bone marrow cells (BMCs)were harvested simultaneously with donor cardiac graft using modified perfusion method (PM) ,then stored in a -80 ℃ refrigerator after filtration and centrifugation. Whole BMCs (IBM-BMT) (monocytes 1.2 ×107/kg,CD34+ cells 2.38× 105/kg) in host iliac bones were injected into the bone marrow cavity 40 days after heart transplantation. Preconditoning regimens that consisted of fludarabine, antithymoctye globin and total lymphoid irradiation were performed 3 days before BMT. Tacrolimus (Tac) was administrated intravenously after BMT or orally in conjunction with mycophenolate mofetil (MMF) 3 weeks later.Cyclosporine and MMF were orally administrated 6 weeks later. Donor chimerism was detected using short tandem repeats-polymerase chain reaction in monocytes from peripheral blood at the 2nd,4th, 8th or 12th week after BMT or BMCs at the 4th, 8th or 12th week after BMT. Intramyocardium electrocardiography examination or endomyocardial biopsy was performed weekly or monthly respectively. Mixed lymphocyte reactions (MLR) were performed 3 months after BMT. Results Donor chimerism in monocytes in peripheral blood or BMCs in iliac bones measured at the 1 st,2nd and 3rd month after BMT was 26.3%, 19.1%,4.8% ,and 46.3%, 24.4%, 7.6%, respectively. After 3-month follow-up, there was no rejection confirmed by endomyocardial biopsy or intramyocardium electrocardiography. Echocardiography revealed that the diastolic and systolic function of the cardiac graft was maintained well 3 months after BMT. MLR revealed donor-specific hyporesponsiveness while immunocompetence was preserved to third-party antigens. Conclusion These findings indicate that the two-stage BMT strategy is a safe and feasible method for the induction of donor-specific tolerance via stable mixed chimerism and needs to be further confirmed after a long-term observation.     

COL8A1siRNA对肝癌细胞体外增殖、侵袭能力及右旋柠烯药敏性的影响

目的 应用RNA干扰技术下调小鼠肝癌细胞株(Hca-F)COL8A1的表达,通过观察癌细胞的体外增殖、侵袭能力,研究调节COL8A1表达对肿瘤细胞药敏性的影响.方法 采用RTPCR、Western Blot分析干扰前后Hca-F细胞中COL8A1的表达情况.用体外侵袭实验检测干扰前后Hca-F细胞的侵袭能力.用MTT法分析干扰前后Hca-F细胞的增殖情况及其对右旋柠烯(D-limonene)的药敏性.结果 Hca-F/RNAi细胞中COL8A1的表达与未给予RNA干扰处理的对照组及RNA干扰对照组相比出现明显下调;该细胞的增殖及穿过基质胶的侵袭能力下降;同时上调该细胞对D-limonene的药敏性.结论 小鼠肝癌细胞中COL8A1的表达与肿瘤细胞的增殖、侵袭及对抗肿瘤药物的敏感性密切相关,可能为肿瘤的化学治疗提供新靶点.

Abstract：

Objective To investigate the possible effects of COL8A1 on the proliferation, invasion and drug sensitivity of murine hepatocarcinoma cell line Hca-F, we used an RNA interference (RNAi) approach to silence COL8A1 expression. Methods The expression levels of COL8A1 in HcaF/siRNA cells were assessed by RT-PCR and Western blot. The inhibitory effect of RNAi on Hca-F cell invasion in vitro was demonstrated by ECM invasion assay. The in vitro proliferative ability and drug sensitivity of COL8A1-deficient cells were determined by MTT assay. Results The expression of COL8A1 was significantly reduced in COL8A1/siRNA cells after 30h transfection, compared with both the RNAi control and the Hca-F cells. The reduced COL8A1 expression also attenuated the proliferative, invasive ability, as well as increased drug sensitivity of Hca-F/siRNA cells. Conclusion Our current results indicate that the expression of COL8A1 functionally mediates tumor cell proliferation, invasion, and drug sensitivity, and is a potential target for therapeutic anti-cancer drugs.     

222例活体肾移植供受者HLA分型配合率的分析

目的 研究活体亲属肾移植供受者HLA配合率,为临床选择良好的供受者HLA配型提供参考.方法 对2006年4月-2008年12月间手术的222例活体亲属肾移植患者进行HLA供受者配合率分析.移植受者男性168例,女性54例,最大年龄58,最小年龄10岁;移植供者男性133例,女性89例,最大年龄64岁,最小年龄21岁.结...     

微创外科技术在结直肠癌伴梗阻治疗中的临床应用

目的探讨记忆金属支架置入技术、腹腔镜手术及植入用缓释氟尿嘧啶局部化疗3种微创外科方法在治疗结直肠癌伴梗阻中的临床应用价值。方法对解放军第251医院、河北北方学院附属第一医院和第三医院2000年5月至2010年5月期间收治的68例结直肠癌伴梗阻患者分别采用下列2种方法治疗:①对可手术根治的结直肠癌伴梗阻患者,先在结肠镜引导下置入记忆金属肠管支架解除梗阻,施行暂时性过渡治疗,再经充分肠道准备后,腹腔镜下施行根治性切除手术;②对失去手术根治机会的晚期(TNMⅣ期)直肠癌患者,主要采用支架置入技术,施行永久性姑息治疗,并经支架网眼穿刺植入缓释氟尿嘧啶局部化疗。结果①采用支架置入技术施行过渡治疗,解除梗阻后采用腹腔镜手术52例,其中51例施行根治性切除,1例因侵袭、转移的乙状结肠癌未能切除。获随访41例,随访时间3~36个月,平均15个月。其中施行根治性切除40例,均无局部复发、切口肿瘤种植及吻合口狭窄,另1例未能切除者于术后93 d死亡。②对15例失去手术根治机会的晚期直肠癌和1例因患严重肺心病不能耐受手术的直肠癌,采用支架置入和植入用缓释氟尿嘧啶治疗,全部获随访,时间为3~24个月,平均14个月;现已死亡11例,其生存时间为(350±222)d(101~720 d);其余5例已存活3~13个月(平均9个月),未再发生肠梗阻。结论利用记忆金属支架与腹腔镜手术联合治疗可手术根治的结直肠癌伴梗阻患者,具有微创、安全等优点;利用记忆金属支架与植入用缓释氟尿嘧啶联合治疗失去手术根治机会的晚期直肠癌伴梗阻,可使患者避免结肠造口,延长其生存期。     

原发ⅡC期结直肠癌患者炎性浸润与癌性浸润预后的比较研究

目的 探讨原发ⅡC期结直肠癌炎性浸润与癌性浸润患者的预后差异及目前临床病理分期的合理性.方法 回顾分析287例原发ⅡC期结直肠癌（结肠癌152例,直肠癌135例）、120例原发ⅡB期结直肠癌（结、直肠癌各60例）及140例ⅢA期无局部浸润结直肠癌患者（结肠癌80例,直肠癌60例）的临床病理资料及随访结果.结果 152例ⅡC期结肠癌患者中癌性浸润组和炎性浸润组患者5年生存率分别为38.5%和59.4%,135例ⅡC期直肠癌患者中癌性浸润组和炎性浸润组患者5年生存率分别为42.1%和62.7%,差异均有统计学意义（均P＜0.001）.ⅡB期结肠癌和直肠癌患者的5年生存率与ⅡC期炎性浸润患者比较,差异均无统计学意义（均P＞0.05）;ⅢA期无局部浸润结肠癌和直肠癌患者的5年生存率则分别低于ⅡC期结肠癌和直肠癌癌性浸润患者（均P＜0.05）.原发ⅡC期结肠癌患者的预后与肿瘤分化程度、有无癌性浸润及术后并发症有关;原发ⅡC期直肠癌患者的预后与肿瘤病理类型、分化程度及有无癌性浸润有关（均P＜0.05）.结论 原发ⅡC期伴癌性浸润结直肠癌患者预后明显劣于ⅡC期炎性浸润者,其临床病理分期有待重新界定：局部有无癌性浸润可作为原发ⅡC期结直肠癌患者的一个独立预后因素.     

血管生成拟态与肿瘤

近年来,人们发现了一种新的肿瘤血供形式——血管生成拟态,其与经典的肿瘤血供模式完全不同.这一发现对完善肿瘤的血供机制,改善肿瘤的治疗和预后具有重要的意义.本文主要就其结构、形成机制、对临床肿瘤治疗的意义进行综述.     

重型颅脑损伤后应激性溃疡防治与胃肠道感染的相关性及对策

目的探讨重型颅脑损伤患者应用洛赛克对应激性溃疡进行防治与胃肠道感染几率增加之间的关系及治疗对策。方法回顾近3年来我院收治的重型颅脑损伤并存活30 d以上病人176例,测定不同时间胃液pH值并分析防治应激性溃疡与发生胃肠道感染的相关性以及相应对策。结果在126例持续应用洛赛克的患者中,持续应用＞7 d的患者胃肠道感染发生率明显高于持续应用≤7 d的病人。其余50例间隔应用洛赛克患者与126例持续应用洛赛克患者相比,应激性溃疡发生率无明显差别,但间隔应用洛赛克患者胃肠道感染发生率较持续应用洛赛克＞7 d的患者明显下降。结论重型颅脑损伤患者应激性溃疡防治＞7 d者,由于胃酸分泌严重抑制,增加胃肠道感染发生率。间隔性应用洛赛克治疗在抑制胃酸分泌,减少应激性溃疡发生的同时,可明显减少胃肠道感染的发生。     

成人型Leigh综合征临床、影像学与神经病理学研究(附一例家系报告)

目的总结成人型Leigh综合征临床、影像学与神经病理学特点,并探讨该病发病机制和诊断标准。方法分析1例Leigh综合征的临床表现、MRI特征和脑组织神经病理特点。结果患者II-4男,32岁,出现共济失调15年,智能障碍10年,脑干症状3个月,32岁死亡。其兄Ⅱ-2,13岁发病,表现为共济失调、痉挛步态伴智能损害,27岁死亡。Ⅱ-4患者MRI-T2加权像可见双侧壳核、尾状核、丘脑、中脑及桥脑被盖对称性高信号病灶;行尸检神经病理检查示,前述部位有多发对称性变性坏死,伴髓鞘脱失、胶质增生和毛细血管增生。结论Leigh综合征可于成人期发病,除临床病程特征外,成人型Leigh综合征与婴幼儿型Leigh综合征在临床、影像学与神经病理学特点诸方面具有相似性,成人患者出现Leigh样症候群应考虑成人型Leigh综合征的可能。