输尿管镜气压弹道碎石治疗输尿管结石110例

目的总结输尿管镜气压弹道碎石治疗输尿管结石的临床效果。方法采用F8/9.8 Wolf硬性输尿管镜、JUN—AIR气压弹道碎石机治疗110例输尿管结石。结果输尿管镜直视下一次碎石成功105例，成功率95．5％（105／110），1～6周内结石全部排净。2例因置镜失败改开放手术，3例输尿管上段结石上移至肾脏行ESWL2例，口服排石药物治疗1例。术后泌尿系感染5例，轻度肉眼血尿1～3d。结论输尿管镜气压弹道碎石是治疗输尿管中、下段结石的有效方法之一，具有碎石率高、安全、并发症少、操作简单的优点。     

小肠间质瘤20例诊治分析

目的　总结小肠间质瘤诊断和治疗经验。方法　对1993—2 0 0 4年收治的2 0例小肠间质瘤的临床资料进行回顾性分析。结果　临床表现为黑便、果酱样血便14例、头晕9例、贫血3例,伴腹部疼痛11例,发病时间2个月至7年。确诊方式:剖腹探查12例,腹腔镜探查6例,小肠镜检查2例;手术方式:小肠间质瘤切除18例,胰十二指肠切除术1例,肿瘤无法切除行保守治疗1例。随访6个月至9年,除1例死于脑干出血、2例长期服用甲磺酸伊马替尼(Gleevec)症状部分缓解外,其余17例均健在,间质瘤无复发。结论　小肠间质瘤预后较好,但对不明原因的消化道出血应及早探查,以避免误诊;Gleevec对晚期小肠间质瘤有较好疗效     

吻合血管神经的(足母)展肌移植修复晚期面瘫

目的:探讨和研究治疗晚期面瘫的手术治疗,总结应用以足底内侧动静脉为蒂的(足母)展肌游离移植一期修复晚期面瘫40例效果和经验.方法:选取(足母)展肌为供肌,以足底内侧动静脉及其延续的胫后动静脉为血管蒂,以支配(足母)展肌神经及其延续的足底内侧神经和胫神经为神经蒂.(足母)展肌移植于患侧面部皮下,肌近断固定于口角,远端固定于耳前颧弓,血管神经蒂通过上唇皮下隧道与健侧面动静脉和面神经颊支吻合.结果:经随访一年以上,23例恢复了面部静态对称和理想的下面部随意和不随意运动;8例恢复了面部静态对称和部分下面部随意和不随意运动;9例仅恢复了面部静态对称.结论:(足母)展肌游离移植一期修复晚期面瘫具有疗效好、手术操作简便、肌肉大小适中、血管神经蒂走行位置恒定紧密伴行、血管神经蒂可切取较长、变跨面神经移植和肌肉移植的两期移植为一期移植等优点;而且,神经是血管化移植.     

External fixation and bone grafting for collapsed and comminuted distal radius fracture

Unstableandcomminutedfractureofthedistalpartoftheradiusremainsachallengingproblem.Thisfracturethatcausedbyhighenergyinjuryisveryunstable,andthereductionandfixationareverydifficult.Inrecentyears,manydifferentexternal fixationdeviceshavebeendevelopedandused.1 4They cankeepthepositionafterreductionwithgood functionalresults.Butforseverecollapsedcases,the bonedefectmayleadtoreductionandfixationfailure orprolongthefracturehealingtime.Thesefinally resultinwristswelling,progressivejointstiffnessand …     

乳晕新月状切口治疗ⅡB|Ⅲ度男性乳房发育症

目的 探讨乳晕新月状切口治疗ⅡB,Ⅲ度男性乳房发育症的临床效果.方法 4年来采用乳晕新月状切口治疗ⅡB,Ⅲ度男性乳房发育症,共25例41侧乳房.结果 每侧乳房切除120～400 g组织.术后5侧乳头、乳晕表皮坏死.经换药后痊愈.早期部分患者乳头、乳晕区轻度凹陷,以后逐渐恢复.随访4～48个月,切口疤痕不明显,外观满意.结论 乳晕新月状切口治疗ⅡB,Ⅲ度男性乳房发育症,操作简便,创伤小,疤痕隐蔽,美体效果好.     

Zoledronate reverses mandibular bone loss in osteoprotegerin-deficient mice

Summary  To characterize the changes in osteoprotegerin-deficient (OPG−/−) mice mandibles and the possible mandibular bone loss prevention by zoledronate. This preventive effect in the mandible differed from that in the proximal tibia and was independent of the OPG pathway. Introduction  The study aimed to characterize both the changes in the mandible in osteoprotegerin-deficient (OPG^−/−) mice and possible mandibular bone loss prevention by zoledronate. Methods  Twenty-eight 6-week-old female mice (C57BL/6J), including OPG^−/− (n = 21) and wild-type (WT) (n = 7) mice, were assigned to four groups after 2 weeks of acclimatization to local vivarium conditions: wild mice with vehicle (WT group); OPG^−/− mice with vehicle (OPG^−/− group); and OPG^−/− mice that were subcutaneously injected with either 50 or 150 μg/kg zoledronate (Zol-50 and Zol-150 groups, respectively). Mice were sacrificed at 4 weeks after these treatments and after fasting for 12 h. Sera were harvested for biochemical analyses. The right mandible and tibia of each mouse were selected for microCT analysis. Student’s t-test was performed for comparisons of bone parameters at different sites in the WT group. Analysis of variance (ANOVA) was used to compare the biomarkers and bone parameters in the different treatment groups. Results  Serum bone-specific alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were significantly decreased in WT mice as compared to the levels in the OPG^−/− mice (P < 0.05). Zoledronate treatment decreased the high serum B-ALP activity observed in OPG^−/− mice to the levels seen in WT mice, while serum TRACP-5b concentrations were decreased to levels even lower than those in WT mice. There were substantial variations in BMD and microstructure of the mandibular and proximal tibial trabeculae. Mandibular bone loss was less affected by OPG gene deprivation than the proximal tibia was. Both zoledronate groups showed greater BMD, trabecular BV/TV, Tb.Th, Tb.N, and Conn.D and a significant decrease in Tb.Sp and SMI as compared to the findings in OPG^−/− mice (P < 0.05). However, higher apparent BMD and more compact plate-like trabeculae were observed in the mandible after treatment with zoledronate as compared to the findings in the proximal tibia. No significant differences were found in any parameter in both zoledronate groups. Conclusions  The present study showed that zoledronate could reverse the significant bone loss in mice mandibles that was induced by OPG gene deficiency. This preventive effect, which was accompanied with considerable inhibition of bone turnover, differed in the mandible and in the proximal tibia and was independent of the OPG pathway. Drs. Sheng and Xu contributed equally to this work.     

The clinical characteristics of renal cell carcinoma in female patients

Objective:   To investigate the clinical characteristics of renal cell carcinoma (RCC) in female patients.
Methods:   The clinical characteristics including sex, age at diagnosis, histological tumor size, histological subtype, Fuhrman nuclear grade and pathological tumor–node–metastasis (TNM) stage of 881 consecutive patients treated with (partial) nephrectomy for RCC from 1998 to 2006 were analyzed. Characteristics of different gender groups and different female age groups were compared. The one-way anova and t -test were used to compare means. Pearson's χ²-test and the likelihood ratio test were used to compare ratios.
Results:   Low-grade tumors accounted for 79.3% of female patients and 64.1% of male patients ( P  < 0.001). The percentage of stage T1–2 was 76.6% in female patients while it was only 68.5% in male patients ( P  = 0.011). Also, female patients had more T1–2N0M0 tumors (73.0% vs 64.3%, P  = 0.009). Once female patients were classified into three groups according to age diagnosis (≤40, 41–59 and ≥60 years) young female patients seemed to have more tumors with unfavorable histology (8.7% vs 5.1% vs 4.3%), Fuhrman grade 3–4 (23.9% vs 23.1% vs 17.7%) and stage T3–4 (28.3% vs 23.1% vs 22.0%).
Conclusion:   Compared with male patients, female patients had lower stage and grade tumors. However, younger female patients had more tumors with unfavorable histology, and higher stage and grade compared to older female patients.     

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.     

跟腱区动脉血供的三维可视化研究

目的通过数字化技术构建跟腱区动脉血供的三维可视化图像,研究跟腱区的动脉血供。方法新鲜人小腿标本三只,用30％明胶、10％朱砂、10％淀粉按比例配制的灌注液灌注,冷藏后CT扫描获得DICOM格式数据,Mimics 10．01软件处理。结果获得小腿跟腱区皮肤、骨骼、动脉、跟腱的三维可视化图像。结论跟腱区三维可视化图像可为临床提供形态学资料,虚拟手术有助于最佳手术方案的选择。     

高效抑制核因子κ—B的茎环RNA基因序列的获得

目的获得高效抑制前列腺癌细胞株Lncap中核因子kappa—B表达的shRNA序列。方法根据核因子kappa—B基因信息,设计siRNA1、siRNA2、siRNA3三条针对核因子kappa-B基因cds区的siRNA序列及无意义的对照序列,组建与之对应的4对互补的单链DNA序列,包括siRNA的正义链和反义链：正义链序列按5’向3’顺序依次为：酶切位点（BamH Ⅰ）、干扰序列（19bp）、loop环（TFCAAGAGA）、干扰序列的反向互补序列（19bp）、中止信号（TTTTT）、酶切位点（EcoR Ⅰ）。将合成的序列插入空载体pSIH1-H1-copGFP shRNA Vector中,转染前列腺癌细胞后,通过real—timePCR检测不同序列片断对核因子kappa—B的mRNA抑制效果。结果设计的3条针对核因子kappa—B的序列中第3条的抑制效果最好,目的序列位于核因子KAPPA—B（NM_021975）的1096到1113,茎环序列为5＇-GATCC GCCCTATCCCTITACGTCA TTCAAGAGA TGACGTAAAGGGATAGGGC TTITT G-3’。其对前列腺癌细胞株中核因子kappa—B的mRNA的干扰效率为59％,对其蛋白表达的抑制率为81％。转染细胞后,细胞可以稳定低表达核因子kappa—B。结论成功获得高效抑制前列腺癌细胞株Lncap中核因子kappa—B表达的shRNA序列,为后期研究核因子kappa-B在前列腺癌发病中的作用机理等研究提供了基础。