肝切除术前门静脉栓塞对围手术期影响的荟萃分析

目的：探讨肝切除术（有半肝、扩大半肝切除术）前应用门静脉栓塞（portal vein embolization,PVE）对病人围手术期的影响。方法：通过电子检索Pubmed、Medline数据库,对1986～2008年有关右半肝或扩大半肝切除术前行PVE病例的对照研究资料进行荟萃分析。结果：共纳入8篇文献．423例病人。荟萃分析结果显示．PVE手术组与单纯手术组比较,术前谷草转氨酶（AST）、总胆红素（TB）、凝血酶原时间（PT）、15min吲哚氰绿储留率（ICGR-15）及肿瘤最大直径两组间均无统计学差异（19〉0．05）;术中输血、肿瘤Rn切除及手术时间两组间均无统计学差异（P〉0．05）。PVE手术组术后感染的发生率显著降低（P=0．002）,但二者在术后出血、胆瘘、肾功能衰竭及术后住院时间的差异无统计学意义（P〉0．05）。结论：术前行PVE不能提高肝脏肿瘤的R0切除率,但能降低术后感染的发生率。     

无骨折脱位型急性外伤性颈髓中央综合征的治疗

目的：分析无骨折脱位型急性外伤性颈髓中央综合征的临床治疗疗效,探讨其治疗方法。方法回顾性分析47例无骨折脱位型急性外伤性颈髓中央综合征患者的临床资料,男44例,女3例;年龄46～73岁,平均56．2岁,脊髓神经功能Frankel分级,B级30例,C级14例,D级3例。对于脊髓有明确的外在致压因素或损伤节段不稳的5例采用手术治疗,其中前路手术3例,后路手术2例,非手术治疗42例。对其致伤原因、致伤机制、影像学表现、神经功能损伤程度、治疗方法及临床疗效进行分析。结果：6例失访,非手术治疗死亡2例。39例术后随访3～84个月,乎均12个月。治疗后3个月内,非手术7例出现并发症,但两组患者后期均有不同程度的肢体神经痛.多数病例遗留手内在肌功能不同程度的损害。结论：根据病情及影像学资料灵活选择治疗方案,保守和手术均可取得良好的治疗结果：     

超声引导在麦默通微创旋切系统治疗乳腺良性肿块中的应用

目的探讨超声引导技术在麦默通（Mammotome）微创治疗乳腺良性肿块中的应用价值。方法197例患者,575枚乳房肿块,经超声检查诊断均为良性肿块,在超声引导下行麦默通微创旋切治疗。结果超声在麦默通微创旋切治疗过程中均能清晰显示病变,引导成功率100%。术后2枚结节病理报告为乳腺浸润性导管癌,超声诊断准确率99.65%（573/575）;6例出现切除部位血肿、5例出现皮下青紫,局部血肿发生率共计5.58%（11/197）。术后3个月超声随访显示5枚病灶少许残留。结论超声引导技术在麦默通旋切治疗乳腺肿块中有重要作用。     

Effects of α1-adrenergic receptor on the proliferation of cholangiocarcinoma cells

Objective To investigate the correlation between α1-adrenergic receptor and the pathological behavior of cholangiocarcinoma, and the effects of norepinephrine (NE) on the proliferation of cholangiocarcinoma cell line QBC939. Methods Thirty-six samples of cholangiocarcinoma were resected in Southwest Hospital from August 2002 to March 2008. The expression of α1-adrenergic receptor in the 36 samples of cholangiocarcinoma tissue and 4 samples of normal bile duct tissue were detected by SABC technique. The proliferation of cholangio-carcinoma cell line QBC939 was detected after processing the cells with NE, phentolamine and prazosin. All the data were analyzed by chi-square test. Results The high positive expression rate of α1-adrenergic receptor was 68% (17/25) in patients with lymph node metastasis, which was significantly higher than 9% (1/11) in patients without lymph node metastasis (χ2=10.604, P<0.05). The high positive expression rate of α1-adrenergic receptor was 85% (11/13) in patients with middle and low positioned cholangiocarcinoma, which was significantly higher than 30% (7/23) in patients with hilar cholangiocarcinoma (χ2=9.753, P<0.05). NE promoted the proliferation of cholangiocarcinoma cell line QBC939 by stimulating the expression of α1-adrenergic receptor, and in a concentration-dependent manner. The proliferative effect was weakened as time passed by, and it was eliminated by phentolamine and prazosin. Conclusions The expression of α1-adrenergic receptor is diverse due to lymph node metastasis and the location of the tumor, α1-adrenergic receptor with high expression may play an important role in the proliferation and metastasis of cholangiocarcinoma.     

西地那非在干预男性肾移植受者移植前后勃起功能时的安全性及有效性研究

目的 评价西地那非在干预男性肾移植受者手术前后勃起功能时的有效性及安全性.方法 选取年龄23～58岁、移植肾存活1年以上、血肌酐在移植后1年内维持在150 μmol/L以下的成年男性肾移植受者41人,所有患者在血液透析期间及移植后均口服两地那非两月,对患者血液透析期间、移植后6月及1年的勃起功能进行调查(依据国际问卷表IIEF-5),记录其各个时段的环孢素浓度、血压及血肌酐.结果 肾移植前与移植后6月及1年患者的ED发生率相比,有显著性差异(P<0.05);不论血液透析期间还是移植后,西地那非治疗后的勃起功能与服药前勃起功能相比,有显著性差异(P<0.05);不论血液透析期间还是移植后,西地那非治疗后的环孢素浓度、血压及肌酐与服药前组相比,无显著性差异(P>0.05).结论 肾移植后,患者的勃起功能得到了改善:不论对于尿毒症血液透析患者,还是肾移植受者,西地那非都可以改善患者的勃起功能,而且两地那非的应用具有安全性.     

后腹腔镜下与开放根治性肾切除术治疗T1肾癌的疗效比较

目的 评价后腹腔镜下肾癌根治术治疗T1肾癌的临床疗效.方法 T1肾癌患者352例,均由同一组医生完成肾癌根治术,其中行后腹腔镜下手术组185例、开放性手术组167例,2组患者年龄、性别、肿瘤大小、分期、SCr值差异均无统计学意义.分析比较2组患者手术时间、术中出血量、住院时间、手术并发症及生存率的差异.结果 后腹腔镜组与开放手术组手术时间为55～130(75.6±11.2)min与50～140(68.0±10.6)min(P0.05);术中出血量50～1200(110.6±32.3)ml与50～1500(160.8±38.1)ml、术后需用止痛药治疗8例与132例、术后进食时间1～2(1.3±0.5)d与2～5(2.9±1.2)d、术后住院时间3～7(4.6±1.2)d与7～1 4(8.9±1.6)d,差异均有统计学意义(P<0.05).术后中位随访时间25(6～42)个月,2组生存率(85.4%与86.2%)差异无统计学意义(P0.05).结论 与开放性肾癌根治术相比,后腹腔镜下肾癌根治术出血少、恢复快、术后并发症少,已成为T1肾癌手术治疗的金标准.     

关节镜下手术松解治疗跟骨骨折后距下关节僵硬

目的 探讨关节镜下手术松解治疗跟骨骨折后距下关节僵硬的临床效果.方法 2004年9月至2006年12月共治疗跟骨骨折后距下关节僵硬患者10例,其中男性8例,女性2例.年龄18～48岁,平均36岁.除2例为双足受累外,其余均为单足病变.根据AOFAS后足活动度分级标准,手术前10足为Ⅲ级,2足为Ⅱ级;AOFAS后足功能评分术前为71.4分.术中患者取侧卧位,分别建立外侧、前外侧、后外侧3种入路,逐步松解前方关节囊、距下关节外侧间隙、跟腓韧带、后方及后内侧关节囊.最后进行手法松解.结果 所有患者均获随访,随访时间12～36个月,平均24.5个月.末次随访时, AOFAS后足活动度分级标准9足后足活动度提高到Ⅰ级,3足提高到Ⅱ级,未见Ⅲ级病例.AOFAS后足功能评分术后为90.6分,与术前比较差异具有统计学意义(P<0.01).所有患者均在术后1～3个月(平均1.8个月)恢复原工作. 结论 关节镜下手术松解治疗跟骨骨折后距下关节僵硬具有微创、操作简单、疗效确切的优点.     

Glucagon-Like Peptide 1/Glucagon Receptor Dual Agonism Reverses Obesity in Mice

OBJECTIVE

Oxyntomodulin (OXM) is a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in obese subjects through increased energy expenditure and decreased energy intake. The metabolic effects of OXM have been attributed primarily to GLP1R agonism. We examined whether a long acting GLP1R/GCGR dual agonist peptide exerts metabolic effects in diet-induced obese mice that are distinct from those obtained with a GLP1R-selective agonist.

RESEARCH DESIGN AND METHODS

We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a corresponding GLP1R-selective agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The metabolic effects of these two peptides with respect to weight loss, caloric reduction, glucose control, and lipid lowering, were compared upon chronic dosing in diet-induced obese (DIO) mice. Acute studies in DIO mice revealed metabolic pathways that were modulated independent of weight loss. Studies in Glp1r^−/− and Gcgr^−/− mice enabled delineation of the contribution of GLP1R versus GCGR activation to the pharmacology of DualAG.

RESULTS

Peptide DualAG exhibits superior weight loss, lipid-lowering activity, and antihyperglycemic efficacy comparable to GLPAG. Improvements in plasma metabolic parameters including insulin, leptin, and adiponectin were more pronounced upon chronic treatment with DualAG than with GLPAG. Dual receptor agonism also increased fatty acid oxidation and reduced hepatic steatosis in DIO mice. The antiobesity effects of DualAG require activation of both GLP1R and GCGR.

CONCLUSIONS

Sustained GLP1R/GCGR dual agonism reverses obesity in DIO mice and is a novel therapeutic approach to the treatment of obesity.Obesity is an important risk factor for type 2 diabetes, and ∼90% of patients with type 2 diabetes are overweight or obese (1). Among new therapies for type 2 diabetes, peptidyl mimetics of the gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) stimulate insulin biosynthesis and secretion in a glucose-dependent manner (2,3) and cause modest weight loss in type 2 diabetic patients. The glucose-lowering and antiobesity effects of incretin-based therapies for type 2 diabetes have prompted evaluation of the therapeutic potential of other glucagon-family peptides, in particular oxyntomodulin (OXM). The OXM peptide is generated by post-translational processing of preproglucagon in the gut and is secreted postprandially from l-cells of the jejuno-ileum together with other preproglucagon-derived peptides including GLP-1 (4,5). In rodents, OXM reduces food intake and body weight, increases energy expenditure, and improves glucose metabolism (6–8). A 4-week clinical study in obese subjects demonstrated that repeated subcutaneous administration of OXM was well tolerated and caused significant weight loss with a concomitant reduction in food intake (9). An increase in activity-related energy expenditure was also noted in a separate study involving short-term treatment with the peptide (10).OXM activates both, the GLP-1 receptor (GLP1R) and glucagon receptor (GCGR) in vitro, albeit with 10- to 100-fold reduced potency compared with the cognate ligands GLP-1 and glucagon, respectively (11–13). It has been proposed that OXM modulates glucose and energy homeostasis solely by GLP1R agonism, because its acute metabolic effects in rodents are abolished by coadministration of the GLP1R antagonist exendin(9–39) and are not observed in Glp1r^−/− mice (7,8,14,15). Other aspects of OXM pharmacology, however, such as protective effects on murine islets and inhibition of gastric acid secretion appear to be independent of GLP1R signaling (14). In addition, pharmacological activation of GCGR by glucagon, a master regulator of fasting metabolism (16), decreases food intake in rodents and humans (17–19), suggesting a potential role for GCGR signaling in the pharmacology of OXM. Because both OXM and GLP-1 are labile in vivo (T_1/2 ∼12 min and 2–3 min, respectively) (20,21) and are substrates for the cell surface protease dipeptidyl peptidase 4 (DPP-4) (22), we developed two long-acting DPP-4–resistant OXM analogs as pharmacological agents to better investigate the differential pharmacology and therapeutic potential of dual GLP1R/GCGR agonism versus GLP1R-selective agonism. Peptide DualAG exhibits in vitro GLP1R and GCGR agonist potency comparable to that of native OXM and is conjugated to cholesterol via a Cys sidechain at the C-terminus for improved pharmacokinetics. Peptide GLPAG differs from DualAG by only one residue (Gln³→Glu) and is an equipotent GLP1R agonist, but has no significant GCGR agonist or antagonist activity in vitro. The objective of this study was to leverage the matched GLP1R agonist potencies and pharmacokinetics of peptides DualAG and GLPAG in comparing the metabolic effects and therapeutic potential of a dual GLP1R/GCGR agonist with a GLP1R-selective agonist in a mouse model of obesity.     

Growth-promoting effect of bisphenol A on neuroblastoma in vitro and in vivo

Purpose

To investigate the effect and mechanism of bisphenol A (BPA), one of the main environmental endocrine disruptors, on the proliferation of human neuroblastoma cells.

Methods

In vitro, cultured SK-N-SH cells were treated with 17β-estradiol (E₂; 1 ng/mL), BPA (2 μg/mL) with or without estrogen receptor antagonist ICI182,780 (10⁻⁶ mol/L). Viable cell number, DNA proliferation index, and expression of cyclin-dependent kinase 4 and cyclin D1 were assessed by absorbance reading, flow cytometry, and western blotting, respectively. In vivo, ovariectomized nude mice bearing SK-N-SH tumors were administered by gavage with E₂ (500 μg/kg per day, n = 11), BPA (200 mg/kg per day, n = 10), or vehicle (n = 9) for 18 days. Mice body weight, tumor volume and weight were examined every 3 days. Tumor microvessel density, proliferating cell nuclear antigen and vascular endothelial growth factor expression were evaluated by immunohistochemical staining or western blotting.

Results

In vitro, the BPA group had 20% higher number of viable cells, 70% higher proliferation index (both P < .01), and higher expression of cyclin-dependent kinase 4 and cyclin D1 than the nontreated group. In vivo, the BPA group had over 50% higher gross tumor volume, tumor weight, microvessel density, proliferating cell nuclear antigen (P < .05 or .01), and higher vascular endothelial growth factor protein expression than the mock control group. Both in vitro and in vivo BPA effects were comparable with those by E₂. ICI182,780 effectively abolished the promoting effect for both.

Conclusions

Bisphenol A can promote the growth of neuroblastoma to a level similar to that of E₂. Estrogen receptor-dependent pathway and angiogenesis may contribute to the underlying mechanisms.     

Proteome analysis of round-headed and normal spermatozoa by 2-D fluorescence difference gel electrophoresis and mass spectrometry

Globozoospermia is a severe form of teratozoospermia characterized by round-headed spermatozoa with an absent acrosome, an aberrant nuclear membrane and midpiece defects. Globozoospermia is diagnosed by the presence of 100% round-headed spermatozoa on semen analysis, and patients with this condition are absolutely infertile. The objective of this study was to investigate the differences in protein expression between human round- headed and normal spermatozoa. Two-dimensional （2-D） fluorescence difference gel electrophoresis （DIGE） coupled with mass spectrometry （MS） was used in this study. Over 61 protein spots were analysed in each paired normal/round-headed comparison, using DIGE technology along with an internal standard. In total, 35 protein spots identified by tandem mass spectrometry （MS/MS） exhibited significant changes （paired t-test, P 〈 0.05） in the expression level between normal and round-headed spermatozoa. A total of nine proteins were found to be upregulated and 26 proteins were found to be downregulated in round-headed spermatozoa compared with normal spermatozoa. The differentially expressed proteins that we identified may have important roles in a variety of cellular processes and structures, including spermatogenesis, cell skeleton, metabolism and spermatozoa motility.