桂枝汤桂枝-白芍不同比例配伍对盐敏感高血压大鼠心脏交感神经过度激活的影响

目的 探讨桂枝汤桂枝-白芍不同比例配伍对盐敏感高血压大鼠心脏交感神经过度激活的影响及其作用机制。方法 将40只6周龄雄性盐敏感大鼠随机分为5组,空白组、模型组、桂枝汤组（桂枝-白芍1∶1组、桂枝-白芍1∶2组和桂枝-白芍2∶1组）每组8只,空白组给予低盐饲料饲养,其余4组给予8%高盐饲料饲养,饲养4周后灌胃,空白组、模型组大鼠每天给予2 mL·kg^-1生理盐水灌胃,桂枝-白芍1∶1组、桂枝-白芍1∶2组和桂枝-白芍2∶1组每天分别按4.0,5.5,5.5 g·kg^-1给予桂枝汤水煎剂灌胃,连续干预4周。IITC多通道无创血压计检测大鼠治疗前后收缩压变化;超声心动图检测左室前壁舒张末期厚度（LVAWd）和室间隔舒张期厚度（IVSd）以反应心肌肥厚程度;苏木素-伊红（HE）染色和马松（Masson）染色观察大鼠心肌形态学变化;蛋白免疫印迹法（Western blot）检测各组大鼠心肌组织神经生长因子（NGF）,生长相关蛋白43（GAP43）和酪氨酸羟化酶（TH）蛋白的表达。结果 桂枝汤干预4周后,与空白组比较,模型组大鼠血压,LVAWd和IVSd显著升高,NGF,TH和GAP43蛋白表达显著增高（P<0.01）;HE和Masson染色结果显示,模型组大鼠心肌细胞水肿,大量炎性细胞浸润,心肌纤维大量增生且排列紊乱,细胞间质可见大量胶原沉积。与模型组比较,桂枝汤各组大鼠收缩压上升缓慢,NGF,TH和GAP43蛋白表达明显降低（P<0.05,P<0.01）,以桂枝-白芍1∶1组效果最佳;超声心动图结果显示,与模型组比较,桂枝-白芍1∶1组可降低LVAWd和IVSd（P<0.05,P<0.01）;桂枝-白芍1∶2组可明显降低IVSd（P<0.05）,但LVAWd与模型组比较,差异无统计学意义;桂枝-白芍2∶1组LVAWd和IVSd均无统计学差异;心肌形态学方面,桂枝汤各组较模型组均可减轻细胞水肿和炎性细胞浸润,减少心肌纤维增生和胶原沉积,改善心肌纤维排列紊乱,其中以桂枝汤桂枝-白芍1∶1组效果最佳。结论 桂枝汤可抑制心脏交感神经系统过度激活,减轻心肌纤维化、炎症浸润和心肌肥厚,对盐敏感高血压大鼠起到保护作用,其机制可能与调节心脏NGF表达有关,其中桂枝汤桂枝-白芍1∶1配伍组在减轻心肌纤维化、炎症浸润和心肌肥厚方面,优于桂枝-白芍1∶2和2∶1组。     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

热断层成像系统鉴别诊断乳腺肿块

目的探讨热断层成像(TTM)检查对女性乳房肿块的诊断价值.方法对78例乳房肿块患者进行TTM检查,其中70例同期行钼靶检查,以手术病理结果为对照.结果78例中TTM诊断恶性病变41例,良性病变37例,真阳性率和真阴性率分别为92.7%和94.6%,钼靶对乳腺肿块的真阳性率和真阴性率分别88.2%和86.1%(P＜0.001).结论TTM对乳腺良、恶性肿块的鉴别诊断具有重要价值.     

Dynesys动态稳定系统治疗多节段腰椎退变性疾病的中远期临床疗效观察

目的:探讨Dynesys动态中和内固定系统治疗多节段腰椎退变性疾病的中远期临床疗效。方法:对2008年12月至2011年5月采用Dynesys系统治疗的多节段腰椎间盘突出症和多节段腰椎管狭窄症28例患者进行回顾性分析。其中男16例,女12例;年龄27～75岁,平均49.1岁。多节段腰椎间盘突出症13例,L₃-L₅ 7例,L₂-L₄ 1例,L₄-S₁ 5例;多节段腰椎管狭窄症15例,L₃-L₅ 10例,L₂-L₅ 4例,L₂-S₁ 1例。所有患者腰腿痛和(或)间歇性跛行症状经正规保守治疗6个月以上无效。记录手术前后患者的腰腿部疼痛视觉模拟评分(Visual analogue scale,VAS),通过影像学资料观察固定节段及头侧邻近节段的椎间隙高度和椎间活动度,采用Oswestry功能障碍指数(Oswestry Disability Index,ODI)对疗效进行评定。结果:28例患者均顺利完成手术,且均获得随访,随访时间38～65个月,平均50.6个月。末次随访时腰腿痛VAS评分分别为1.25±0.70和1.29±0.89,ODI为(25.10±6.52)%,腰腿痛VAS评分及ODI较术前有明显下降(p<0.05).术后随访固定节段椎间隙高度较术前有所升高,椎间活动度下降,与术前比较差异有统计学意义(p<0.05).术前及术后各随访时间点头侧邻近节段活动度、椎间隙高度差异无统计学意义(p>0.05).结论:Dynesys治疗多节段腰椎退变性疾病中远期临床疗效满意,能保留部分椎间活动度,对邻近节段影响小。Dynesys远期临床疗效还有待更长时间的随访观察。     

Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients

Aim:

Eukaryotic translation initiation factor 3 subunit A (eIF3a) plays critical roles in regulating the initiation of protein translation, and eIF3a is highly expressed in lung cancer. In this study, we investigated the association of the positively selected SNPs of eIF3a with the response to and toxicity of platinum-based chemotherapy in Chinese patients with non-small cell lung cancer (NSCLC).

Methods:

SNP data for eIF3a locus were downloaded from HapMap database. For each SNP, haplotype, LD profile and population differentiation were analyzed. The long-range haplotype (LRH) test was employed to identify positively selected SNPs of eIF3a. A total of 325 NSCLC patients were enrolled and genotyped for these SNPs.

Results:

Five positively selected (rs1409314, rs4752219, rs4752220, rs7091672 and rs10510050) and 5 non-positively selected SNPs (rs10886342, rs11198804, rs2275112, rs10787899 and rs4752269) were identified in the LRH test. However, none of them was correlated with the platinum-based chemotherapy response. In contrast, 4 of the positively selected SNPs (rs1409314, rs4752219, rs4752220 and rs7091672) were significantly correlated with the toxicities tested (neutropenia, anemia, thrombocytopenia, emesis and hepatotoxicity). In addition, rs10510050 was significantly correlated with thrombocytopenia, emesis and hepatotoxicity. None of the 5 non-positively selected SNPs was correlated with the 5 toxicities.

Conclusion:

The positively selected SNPs of eIF3a are significantly correlated with platinum-based chemotherapy toxicities in Chinese NSCLC patients.     

SD大鼠脏器重量及脏器系数正常参考值的确立与应用

目的确定本中心不同周龄SD大鼠脏器重量与脏器系数的正常参考值范围,为药物安全性评价与研究提供重要参考数据。方法以本中心近7年开展的SD大鼠长期毒性实验中空白对照组动物为数据来源,分为8～12、12～24及24～36周龄3个年龄段,每年龄段包括雌性、雄性大鼠各200只,分别统计各年龄段雌性、雄性动物的脑、心脏、肺脏、肝脏、脾脏、肾脏、肾上腺、胸腺、睾丸、附睾、卵巢与子宫等脏器重量与脏器系数,以95%可信区间作为正常参考值范围。结果与结论本中心8～12、12～24及24～36不同周龄SD大鼠脑、心脏、肺脏、肝脏、脾脏、肾脏、肾上腺、胸腺、睾丸、附睾、卵巢与子宫等脏器重量及脏器系数的正常参考值范围与其他实验室报道的结果可比性良好。     

Dashboard (in the) Knee

We present the case of a 19-year-old individual presenting to an orthopaedic outpatient clinic several months following a dashboard knee injury during a road traffic accident with intermittent mechanical symptoms. Despite unremarkable examination findings and normal magnetic resonance imaging, the patient was identified subsequently as having an intra-articular plastic foreign body consistent with a piece of dashboard on arthroscopic knee assessment, the retrieval of which resulted in a complete resolution of symptoms.     

牵拉应力在5-氮杂胞苷诱导骨髓间充质干细胞成肌过程中的动态效应

背景:国内外研究发现在一定力学环境下,体外培养的间充质干细胞其增殖分化等一系列生物学特性会发生相应变化.目的:体外观察5-氮杂胞苷与牵拉应力对大鼠骨髓间充质干细胞向肌细胞分化的调控作用.设计、时间及地点:2006-01/2007-06在上海交通大学牛物力学实验室完成的细胞观察实验.材料:清洁级3-4周龄雄性SD大鼠30只用于分离培养骨髓间充质干细胞,1～3d龄SD新生鼠4只用于建立骨骼肌阳性细胞株.化学诱导剂5-氮杂胞苷为Sigma公司产品,牵拉设备Fx-4000 Flexercell由美国Flexcell Int公司生产.方法:将传至第4代的骨髓间充质干细胞接种于Flex 6孔板.[1]设立5组行成肌家族因子表达Western-Blot检测:第1组细胞单纯经10μmol/L 5-氮杂胞苷诱导1周;第2～4组细胞以10μmol/L 5-氮杂胞苷诱导1周后,在1Hz频率、15%幅度应力条件下分别牵拉12,24,36h;第5组以新生鼠骨骼肌细胞作为阳性对照.[2]设立5组行诱导剂及牵拉应力作用的RT-PCR检测:第1组细胞给予1Hz频率、15%幅度应力牵拉24h;第2、3组分别经10μmol/L 5-氮杂胞苷诱导1,2周;第4组细胞经10μmol/L 5-氮杂胞苷诱导2周后,给与同等应力牵拉24h;第5组以新生鼠骨骼肌细胞作为阳性对照.主要观察指标:不同诱导条件及应力牵拉状态下骨髓间充质干细胞成肌家族因子的表达.结果:[1]第1组表达成肌因子MyoD与Myf5,成熟肌细胞标志MHC表达不显著;第2～4组MyoD与Myf5的表达明显增强(P<0.05),且随牵拉时间延长因子的表达逐步增强,MHC表达不显著.[2]第1组不表达成肌家族因子;第2组表达MyoD、 Myf5,第3组表达MyoD、 Myf5、 desmin,第4组几乎表达所有检測的肌细胞特异性标记.结论:经5-氮杂胞苷诱导可启动骨髓间充质干细胞向肌细胞分化,单独的牵拉应力不能诱导成肌.牵拉应力可调控5-氮杂胞苷对骨髓间充质干细胞的诱导分化进程,并且与牵拉作用时间成正性相关.