船员屈指肌腱损伤的治疗

目的探讨船员屈指肌腱损伤的特点和治疗方法。方法对本院收治的５２例船员屈指肌腱损伤临床资料进行总结并着重对治疗效果进行分析。结果本组Ⅰ期修复４３例１６８条,Ⅱ期修复９例２４条。术中用套圈缝合法或改良Ｋｅｓｓｌｅｒ法缝接肌腱,Ⅱ期行粘连肌腱松解术８例２５条,术后２４小时开始功能锻炼。治疗效果经对４３例１４６条随访３个月～３年（平均１年６个月）,根据ＴＡＭ疗效标准评定为：锐割伤５７条中,优４７条,良８条,中２条,优良率为９６．５％;缆绳绞轧伤３６条中,良２１条,中９条,差６条,优良率为５８．３％;压榨断开伤５３条中,优２９条,良１６条,中６条,差２条,优良率为８４．９％。结论屈指肌腱损伤疗效与损伤类型关系密切。锐器切割伤疗效最佳,缆绳绞轧伤最差。对缆绳绞轧伤应积极创造条件,采取相应措施,以提高其疗效     

ULK1在胃癌中的表达及其临床意义

目的 探讨胃癌组织中ULK1的表达及其临床意义。方法 收集2013年1月至2013年12月145例胃癌组织和50例癌旁组织。采用免疫组化SP法检测上述组织中ULK1的表达,分析其表达与临床病理特征和预后的关系。结果 胃癌组织和癌旁组织中ULK1的阳性表达率分别为80％（116／145）和16％（8／50）,差异有统计学意义（P＜0.05）。ULK1表达与胃癌浸润深度、分化程度、淋巴结侵犯、TNM分期和复发转移有关（P＜0.05）,与年龄、脉管侵犯、HER 2和p53无关（P＞0.05）。ULK1无表达、低表达和高表达组患者的中位生存时间分别为44.8个月（95％CI：40.5～49.2个月）、427个月（95％CI：39.9～45.6个月）和37.7个月（95％CI：33.0～42.4个月）,差异有统计学意义（P=0.007）。     

阿米替林对大鼠间质性膀胱炎的治疗作用

目的探索小剂量环磷酰胺长期慢性腹腔注射建立大鼠间质性膀胱炎(interstitial cystitis,IC)模型的方法,并研究阿米替林对IC的治疗作用。方法 42只SD大鼠,采用随机数字表法分为7组:对照组,4、48 h模型组,10、30、45 d模型组和治疗组。模型组和治疗组腹腔注射环磷酰胺(cyclophosphamide,CYP)40 mg/kg,治疗组于第31天开始给予阿米替林10 mg/(kg·d)灌胃,持续15 d。观察膀胱组织大体、光镜及电镜形态学表现。通过ELISA检测对照组和30、45 d模型组以及治疗组血清中IL-6、IL-10、IL-17A水平的变化。结果模型组大鼠表现出IC的病理学变化。30、45 d模型组血清中IL-6、IL-10、IL-17A水平均较对照组升高(P<0.05);治疗组较45 d模型组降低,但高于对照组,差异均有统计学意义(P<0.05)。结论环磷酰胺小剂量慢性作用可构建大鼠IC模型,阿米替林可以改善IC大鼠的病理学表现。     

Methylprednisolone inhibits Nogo-A protein expression after acute spinal cord injury

Oligodendrocyte-produced Nogo-A has been shown to inhibit axonal regeneration. Methylprednisolone plays an effective role in treating spinal cord injury, but the effect of methylprednisolone on Nogo-A in the injured spinal cord remains unknown. The present study established a rat model of acute spinal cord injury by the weight-drop method. Results showed that after injury, the motor behavior ability of rats was reduced and necrotic injury appeared in spinal cord tissues, which was accompanied by increased Nogo-A expression in these tissues. After intravenous injection of high-dose methylprednisolone, although the pathology of spinal cord tissue remained unchanged, Nogo-A expression was reduced, but the level was still higher than normal. These findings implicate that methylprednisolone could inhibit Nogo-A expression, which could be a mechanism by which early high dose methylprednisolone infusion helps preserve spinal cord function after spinal cord injury.     

慢性乙型肝炎患者血清铁调素和铁代谢指标及体外HBV转染Huh7细胞铁调素水平变化*

目的 探讨慢性乙型肝炎(CHB)患者血清铁调素(Hepc)和铁代谢指标的变化,并在体外观察HBV转染肿瘤细胞Hepc表达的变化。方法 在71例CHB患者和24例健康体检者,采用ELISA法检测血清Hepc水平,使用全自动蛋白分析仪检测血清铁(SI)、铁蛋白(Ferr)和转铁蛋白(Tf)水平。使用电化学发光全自动免疫分析仪检测血清IL-6水平。构建HBV感染Huh7细胞模型,分别采用RT-qPCR和Western blot法检测细胞Hepc表达情况。结果 与健康人比较,CHB组血清SI、Ferr、IL-6、丙氨酸氨基转移酶 (ALT)、天门冬氨酸氨基转移酶(AST)、血清总胆红素 (TBIL)水平均显著升高,Hepc、Tf和可溶性转铁蛋白受体(sTfR)、白蛋白(ALB)显著降低(P<0.05);转染细胞24 h,Hepc mRNA相对水平为(5.21±0.43),空白对照细胞的(0.73±0.14)显著升高(P<0.05),在转染48 h,细胞Hepc mRNA水平为(8.45±0.61),较空白对照的(1.16±0.17)显著升高(P<0.05);在质粒转染48 h后,细胞Hepc蛋白相对表达量为(0.78±0.08),较空白对照的(0.41±0.02)显著升高(P<0.05)。结论 检测铁调素及其铁代谢相关指标有助于评估慢性乙型肝炎病情进展,适当予以铁调素或者其相应内源性激活剂针对性地治疗铁超载CHB患者,是否可应用于临床,值得期待。     

吉马酮对缺氧缺糖损伤BMECs细胞抗凝和纤溶功能的影响

目的:研究吉马酮对缺糖缺氧(OGD)损伤的原代大鼠微脑血管内皮细胞(BMECs)抗凝和纤溶等功能的影响。方法:通过使用DMEM F12无糖培养液,并将其放入含95%N2、5%CO2混合气体的缺氧小室中培养6h,从而建立原代BMECs细胞缺氧缺糖模型。利用MTT法检测细胞增殖率及细胞毒性;ELISA法检测6-keto-PGF1α、ET-1、t-PA和PAI-1;硝酸还原酶法检测NO等。结果:在20~200μmol/L范围内随着浓度的增大吉马酮对细胞的增殖作用增强,而超过范围后抑制细胞生长。与正常组比较缺氧缺糖损伤使6-keto-PGF1α、NO、t-PA、SOD和GSH-Px含量降低,PAI-1、ET-1、LDH、MDA含量增加;与模型组比较吉马酮(11、22、44mg/L)使6-keto-PGF1α、NO、t-PA、SOD和GSH-Px含量增加,PAI-1、ET-1、LDH、MDA含量减少。结论:缺氧缺糖损伤BMECs细胞使其分泌功能下降,且凝血和纤溶功能出现异常;吉马酮对缺氧缺糖损伤BMECs细胞具有保护作用,并调节BMECs细胞的分泌功能及凝血和纤溶功能。     

ac18 is not essential for the propagation of Autographa californica multiple nucleopolyhedrovirus

orf18 (ac18) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a highly conserved gene in lepidopteran nucleopolyhedroviruses, but its function remains unknown. In this study, an ac18 knockout AcMNPV bacmid was generated to determine the role of ac18 in baculovirus life cycle. After transfection of Sf-9 cells, the ac18-null mutant showed similar infection pattern to the parent virus and the ac18 repair virus with respect to the production of infectious budded virus, occlusion bodies, or the formation of nucleocapsids as visualized by electron microscopy. The deletion mutant did not reduce AcMNPV infectivity for Trichoplusia ni in LD(50) bioassay; however, it did take 24 h longer for deleted mutant to kill T. ni larvae than wild-type virus in LT(50) bioassay. Our results demonstrate that ac18 is not essential for viral propagation both in vitro and in vivo, but it may play a role in efficient virus infection in T. ni larvae.     

Two ⁹⁰Y-labeled multimeric RGD peptides RGD4 and 3PRGD2 for integrin targeted radionuclide therapy

We have recently developed a series of new Arg-Gly-Asp (RGD) dimeric peptides for specific targeting of integrin α(v)β? with enhanced tumor uptake and improved pharmacokinetics. In this study, we investigated ??Y-labeled RGD tetramer (RGD4) and the new type of RGD dimer (3PRGD2), for the radionuclide therapy of integrin α(v)β?-positive tumors. Biodistribution and gamma imaging studies of 111In labeled RGD4 and 3PRGD2 were performed. Groups of nude mice were used to determine maximum tolerated dose (MTD) of ??Y-DOTA-RGD4 and ??Y-DOTA-3PRGD2. The radionuclide therapeutic efficacy of ??Y-DOTA-RGD4 and ??Y-DOTA-3PRGD2 was evaluated in U87MG tumor-bearing nude mice. The U87MG tumor uptake of 111In-DOTA-3PRGD2 was slightly lower than that of the 111In-DOTA-RGD4 (e.g., 6.13 ± 0.82%ID/g vs 6.43 ± 1.6%ID/g at 4 h postinjection), but the uptake of 111In-DOTA-3PRGD2 in normal organs, such as liver and kidneys, was much lower than that of 111In-DOTA-RGD4, which resulted in much higher tumor-to-nontumor ratios and lower toxicity. The MTD of ??Y-DOTA-RGD4 in nude mice is less than 44.4 MBq, while the MTD of ??Y-DOTA-3PRGD2 in mice is more than 55.5 MBq. ??Y-DOTA-3PRGD2 administration exhibited a similar tumor inhibition effect as compared with ??Y-DOTA-RGD4 at the same dose. The tumor vasculature in the ??Y-DOTA-3PRGD2 treatment group was much less than the control groups. Radionuclide therapy studies exhibited that both ??Y-DOTA-RGD4 and ??Y-DOTA-3PRGD2 caused significant tumor growth delay in the U87MG tumor model. Compared to ??Y-DOTA-RGD4, the low accumulation of ??Y-DOTA-3PRGD2 in normal organs led to lower toxicity and higher MTD in nude mice, which would make it more suitable for high dose or multiple-dose regimens, in order to achieve maximum therapeutic efficacy.     

艾司西酞普兰对慢性前列腺炎大鼠行为学的影响

目的：建立慢性前列腺炎（Chronic prostatitis,CP）动物模型并观察其行为学变化,探讨CP的发病机制和临床治疗。方法：50只雄性SD大鼠,随机分成6组：正常对照组、模型组45、60、90 d（每组10只）;治疗15 d组、治疗45 d组（每组5只）。模型组和治疗组大鼠均采用免疫佐剂法造模,治疗组于造模第46天开始给予艾司西酞普兰（Escitalopram）10 mg/（kg·d）灌胃,分别持续15 d和45 d。通过开野实验和糖水消耗试验观察各组大鼠的行为学表现;模型组45、60、90 d处死大鼠取材,治疗组用药后15、45 d取材,观察前列腺组织的大体、光镜病理形态学表现。结果：实验大鼠50只全部进入结果分析。90 d模型组的水平运动和垂直运动次数得分及糖水消耗量[（47.40±17.45）、（5.90±2.80）、（53.80±16.29） ml/24 h]与正常对照组[（70.40±10.35）、（12.80±4.69）、（88.21±21.66） ml/24 h]比较明显减少（P=0.017,P=0.038,P=0.048）,差异有统计学意义;与正常组对照比较,45、60 d模型组、治疗15 d组及治疗45 d组的水平运动、垂直运动次数和糖水消耗量的差异无统计学意义（P >0.05）。结论：90 d CP模型大鼠表现出抑郁症状,艾司西酞普兰可改善CP大鼠的病理学表现和抑郁行为。     

基于公共数据库构建肺腺癌肿瘤干性评分模型预测免疫治疗疗效

目的 鉴定肺腺癌肿瘤干细胞相关基因亚型,构建肿瘤干性评分模型以预测肺腺癌免疫检查点抑制治疗疗效。 方法 从TCGA数据库下载肺腺癌RNA测序数据,使用“limma”包分析肺腺癌(535例)与癌旁组织(59例)中329个肿瘤干细胞相关基因的差异表达(FDR<0.05, |log₂ Fold Change|>2),利用差异基因鉴定肺腺癌肿瘤干细胞相关亚型,通过单因素Cox回归分析进一步筛选出肿瘤干细胞相关亚型之间对预后有意义的共同差异基因。基于主成分分析(PCA)算法,利用123个预后有意义的共同差异基因对TCGA与GEO合并后的630例肺腺癌患者进行肿瘤干性评分,利用Kaplan-Meier 曲线分析确定最佳截断值,将肺腺癌患者分成高、低肿瘤干性评分组(截断值为-1.91)。探究不同肺腺癌肿瘤干细胞相关亚型和肿瘤干性评分组在肿瘤微环境、免疫治疗方面的差异。 结果 鉴定出了36个差异表达基因和3个预后有统计学意义的肿瘤干细胞相关亚型(CSC-A、 CSC-B、 CSC-C)(P=0.033),其在免疫细胞浸润方面差异有统计学意义并与抗原递呈、细胞毒性作用等多条免疫通路相关。单因素Cox回归分析筛选出123个对预后有意义的共同差异基因,构建了肿瘤干性评分模型。低肿瘤干性评分组各类免疫细胞浸润程度普遍上升,PD1、PD-L1、CTLA4表达显著升高。无论是单独的抗CTLA4或抗PD1治疗,亦或是二者联合治疗,低肿瘤干性评分组的疗效都优于高肿瘤干性评分组,无免疫检查点抑制治疗时,高、低肿瘤干性评分组的疗效差异无统计学意义(P=0.060)。在抗PD-L1和抗PD1的两个独立免疫治疗队列中,低肿瘤干性评分组的反应率均高于高肿瘤干性评分组(抗PD-L1治疗队列反应率:50% vs 20%;抗PD1治疗队列反应率:23% vs 0%)。 结论 肿瘤干性评分模型在预测肺腺癌患者免疫检查点抑制治疗疗效方面具有潜在价值,有望为肺腺癌患者免疫检查点抑制治疗提供理论依据。