结直肠癌常用化疗药引起肝损伤的研究

目的：以奥沙利铂、伊立替康等为主的化疗方案在结直肠癌肝转移中的应用逐渐增加,但目前一些临床观察表明,化疗可能影响肝脏损伤,进而影响新辅助化疗后围手术期的死亡率。本研究的目的是在健康小鼠腹腔中注射常用化疗药,明确应用不同化疗药引起肝损伤的类型及严重程度。方法：昆明小鼠反复腹腔注射生理盐水或伊立替康、奥沙利铂、5-FU/伊立替康及5-FU/奥沙利铂联合化疗。注射后处死小鼠,以组织学改变评估肝脏损伤类型。结果：在最大可耐受剂量下使用各种化疗药物,肝组织学未显示脂肪变性、纤维化或炎性浸润。与仅接受生理盐水腹腔注射的小鼠相比,接受5-FU/奥沙利铂联合化疗后小鼠肝组织VEGF mRNA表达水平无显著差异。结论：在无肿瘤负荷前提下,以5-FU、伊立替康、奥沙利铂为主的化疗,无肝损伤发生。此外,联合治疗也没有引起组织学改变。     

肾脏占位病变的超声造影诊断及鉴别诊断

目的 探讨超声造影对肾脏占位病变的诊断价值,提高其诊断及鉴别诊断水平.方法 对35例经穿刺或手术病理结果证实为肾脏占位病变患者的超声造影表现进行回顾分析,观察其增强程度、增强均匀度、假包膜征、增强、消退时间及增强方式.结果 超声造影示恶性肿瘤28例,良性病变7例.恶性肿瘤中肾癌17例,肾盂癌11例;良性病变中肾血管平滑肌脂肪瘤4例,肾囊肿3例.肾癌多表现为快进快出、弥漫性不均匀性明显增强及假包膜形成;肾盂癌多表现为慢进快出和弥漫性均匀性不明显增强;肾血管平滑肌脂肪多表现为快进慢出和向心性均匀性不明显增强;肾囊肿多表现为无增强.结论 超声造影对肾脏占位病变的诊断和良恶性病变的鉴别诊断有较高价值.     

Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts

Mice deficient in Schnurri-3 (SHN3; also known as HIVEP3) display increased bone formation, but harnessing this observation for therapeutic benefit requires an improved understanding of how SHN3 functions in osteoblasts. Here we identified SHN3 as a dampener of ERK activity that functions in part downstream of WNT signaling in osteoblasts. A D-domain motif within SHN3 mediated the interaction with and inhibition of ERK activity and osteoblast differentiation, and knockin of a mutation in Shn3 that abolishes this interaction resulted in aberrant ERK activation and consequent osteoblast hyperactivity in vivo. Additionally, in vivo genetic interaction studies demonstrated that crossing to Lrp5^–/– mice partially rescued the osteosclerotic phenotype of Shn3^–/– mice; mechanistically, this corresponded to the ability of SHN3 to inhibit ERK-mediated suppression of GSK3β. Inducible knockdown of Shn3 in adult mice resulted in a high–bone mass phenotype, providing evidence that transient blockade of these pathways in adults holds promise as a therapy for osteoporosis.     

Serum tumour markers in patients with chronic kidney disease

Objective. Tumour markers are widely used for monitoring cancer patients and for screening certain tumours. It has recently been shown that the concentrations of some tumour markers are higher in patients with chronic kidney disease (CKD) than in healthy subjects. We analysed the influence of renal function and hemodialysis treatment on the serum levels of CA19‐9, CA125, alpha fetoprotein (AFP), CA15.3, CA72.4, CYFRA 21‐1, neuron‐specific enolase (NSE) and squamous cell carcinoma antigen (SCC‐Ag). Material and methods. 232 non‐dialysis patients with CKD and 37 uraemic patients treated with maintenance hemodialysis were enrolled in this study. The non‐dialysis patients were divided into three groups depending on their creatinine clearance (Ccr) levels: group 1 = Ccr ?25?mL/min; group 2 = 25.1–49.9?mL/min; group 3 = Ccr ?50?mL/min. For comparison, we chose 37 non‐dialysis patients with similar Ccr, age and same gender as controls. Results. The serum concentrations of CA19‐9, CA125 (male), CYFRA 21‐1, NSE and SCC‐Ag correlated negatively with Ccr, while there were no significant differences in the concentrations of CA125 (female), AFP, CA15.3, CA72.4. The serum levels of CA19‐9, CA125, AFP, CA15.3, CA72.4, CYFRA 21‐1, NSE and SCC‐Ag showed no differences between hemodialysis patients and non‐dialysis controls (p>0.017). Conclusions. The increase in the serum levels of CA19‐9, CA125 (in males), CYFRA 21‐1, NSE and SCC‐Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19‐9, CA125, AFP, CA15.3, CA72.4, CYFRA 21‐1, NSE and SCC‐Ag.     

低分子肝素与分次给予普通肝素治疗进展型脑梗死临床疗效对比

目的观察普通肝素钠与低分子量肝素钠治疗进展型脑梗死临床疗效及其安全性。方法将72例急性进展性脑梗死患者随机分为治疗组(36例)与对照组(36例),两组除常规治疗外,治疗组加用肝素钠50mg,2/d静脉滴注,连用5d。对照组给予低分于肝素钠5000U皮下注射,2/d,连用5d,于治疗前和治疗后14d比较两组神经功能缺缺损程度评分。结果治疗组神经功能缺损积分较对照组明显减少(P>0.05)。结论普通肝素分次静点较低分子量肝素钠治疗进展型脑梗死疗效好且相对安全。     

Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin

The platelet-specific chemokine platelet factor 4 (PF4) is released in large amounts at sites of vascular injury. PF4 binds to heparin with high affinity, but its in vivo biologic role has not been defined. We studied the role of PF4 in thrombosis using heterozygote and homozygote PF4 knock-out mice (mPF4(+/-) and mPF4(-/-), respectively) and transgenic mice overexpressing human PF4 (hPF4(+)). None of these lines had an overt bleeding diathesis, but in a FeCl(3) carotid artery thrombosis model, all showed impaired thrombus formation. This defect in thrombus formation in the mPF4(-/-) animals was corrected by infusing hPF4 over a narrow concentration range. The thrombotic defect in the mPF4(+/-) and mPF4(-/-) animals was particularly sensitive to infusions of the negatively charged anticoagulant heparin. However, the same amount of heparin paradoxically normalized thrombus formation in the hPF4(+) animals, although these animals were anticoagulated systemically. Upon infusion of the positively charged protein, protamine sulfate, the reverse was observed with mPF4(+/-) and mPF4(-/-) animals having improved thrombosis, with the hPF4(+) animals having worsened thrombus formation. These studies support an important role for PF4 in thrombosis, and show that neutralization of PF4 is an important component of heparin's anticoagulant effect. The mechanisms underlying these observations of PF4 biology and their clinical implications remain to be determined.     

高强度聚焦超声和子宫切除手术治疗子宫腺肌瘤的有效性及其成本效用分析

目的探讨高强度聚焦超声（HIFU）和子宫切除手术治疗子宫腺肌瘤有效性,并进行成本效用分析。方法将40例子宫腺肌瘤的患者均分为HIFU组和子宫切除组,于治疗后1、3、6个月随访患者治疗前后生活质量（QOL）改善率,并采用等级尺度法提取效用值进行成本效用分析。结果两组治疗后各时间点的QOL评分差异无统计学意义（P〉0．05）;但各组内QOL在治疗6个月后均较前升高（P〈0．05）,HIFU组和手术组的质量调整生命年成本分别为20388．76元／年和34507．68元／年,增量成本效用分析和敏感性分析表明手术组的花费高于HIFU组。结论HIFU和手术治疗均可有效改善子宫腺肌瘤患者的生存质量,6个月内手术治疗成本较高。     

凝血酶原G20210基因多态性与中国汉族人群肺血栓栓塞症的相关性

目的探讨凝血酶原基因3’端非翻译区20210 G/A多态性与中国汉族人群肺血栓栓塞症(PTE)发生的相关性。方法采用病例-对照研究,病例组为经放射性核素肺通气/灌注显像和(或)螺旋CT肺动脉造影(CTPA)检查,并结合临床资料确诊的PTE患者101例;对照组为与PTE患者来自相同地区,性别、年龄相匹配的健康对照101例。应用碘化钾-氯仿-异丙醇法提取基因组。应用聚合酶链反应(PCR)、HindⅢ限制性内切酶片段长度多态性分析(RFLP)及聚丙烯酰胺凝胶电泳(PAGE)等方法检测凝血酶原G20210多态性。结果健康对照人群GⅡ20210A位点的基因频率符合Hardy-Weinberg平衡定律,PTE病例组及对照组GⅡ20210A位点均为野生型(GG)纯合子,GA、AA基因型频率为0,A等位基因频率为0。结论凝血酶原G20210A基因多态性与中国汉族人群PTE发生可能无关。     

HPLC紫外检测法测定血浆甲磺酸瑞波西汀浓度

目的建立测定血浆甲磺酸瑞波西汀浓度的高效液相色谱检测法。方法以麦普替林为内标,取血浆样本1mL,用饱和Na2HPO4碱化后以重蒸乙醚5mL提取,再用0.2mol.L-1盐酸0.2mL反提取,80℃～100℃热水浴下氮气吹干盐酸层,用50μL流动相重组后进样。采用InertsilODS-3柱(GLSciense,5μm,4.6mm×150mm)进行分离。流动相为乙腈-50mmol/L磷酸钠缓冲液(pH=6)(40:60,v/v),流速为0.6mL.min-1,紫外检测波长210nm。结果瑞波西汀对内标的峰高比与血浆甲磺酸瑞波西汀浓度直线相关,相关系数r=0.9997,线性范围3.12～200ng.mL-1。甲磺酸瑞波西汀的最低检测限0.5ng,最低检测浓度2ng.mL-1,提取回收率在82.50%～86.08%之间,批内和批间RSD分别为2.02%～5.33%和3.83%～8.50%。结论本法具有较高的灵敏度、精密度和特异性,适用于甲磺酸瑞波西汀的药代动力学和治疗药物监测的研究。