趋化因子受体7在膀胱癌组织中的表达及其临床意义

目的 探讨趋化因子受体7(CXCR7)蛋白在膀胱癌中的表达情况,并分析其与临床生物学行为及复发的关系.方法 选择148例膀胱移行细胞癌标本,30例正常膀胱组织标本:肿瘤标本中非肌层浸润性癌104例,肌层浸润性癌44例;G147例、G2 73例、G3 28例;单发肿瘤89例,多发肿瘤59例;非肌层浸润性癌中未复发40例,复发64例.采用LSAB免疫组织化学方法,检测膀胱癌和正常组织中CXCR7蛋白的表达,并结合临床资料进行分析. 结果正常组织中CXCR7蛋白的表达水平为10.0%(3/30),肿瘤组织为85.1%(126/148);单发及多发肿瘤CXCR7蛋白高表达率分别为49.4%(44/89)和71.2%(42/59),G1、G2、G3膀胱癌CXCR7蛋白高表达阳性率分别为34.0%(16/47)、65.8%(48/73)、78.6%(22/28),差异均有统计学意义(P＜0.01).非肌层浸润性肿瘤和肌层浸润性肿瘤中CXCR7蛋白高表达阳性率为51.9%和72.7%,组间差异有统计学意义(P＜0.05).非肌层浸润性膀胱癌中,复发组与未复发组中CXCR7蛋白高表达阳性率为64.1%和32.5%,差异有统计学意义(P＜0.01).Kaplan-Merier曲线显示,CXCR7蛋白高表达组患者和CXCR7蛋白低表达组患者术后无复发生存率比较,差异有统计学意义(P＜0.01). 结论CXCR7蛋白高表达与膀胱移行细胞癌的恶性程度及预后相关,提示CXCR7与膀胱癌的发生发展存在相关性.

Abstract：

Objective To explore the expression of CXCR7 in bladder cancer and analyze its clinical significance and relationship with bladder cancer recurrence. Methods The expressions of CXCR7 protein in 148 specimens of bladder cancer and 30 specimens of normal bladder tissues were detected by immunohistochemical staining and its clinical significance was then analyzed. Results The expression of CXCR7 protein was higher in bladder cancers than in the adjacent normal tissues (P＜0.01). CXCR7 protein expression rates were 49. 4% and 71.2% in mutifocal tumors and unifocal tumors, while 34.0%, 65.8% and 78. 6% in G1, G2, and G3 tumors, respectively (P＜0. 01). Expression of CXCR7 protein was higher in muscle invasive bladder cancers than in non-muscle invasive bladder cancers (72. 7% versus 51.9% ,P＜0.05). In patients followed up for 2-95 months, CXCR7 protein expression was significantly higher in patients with recurrence than with non-recurrence (64. 1% versus 32.5%, P＜0.01). Kaplan-Meier analysis and the log-rark test showed that the recurrence-free survival was significantly different between the group of lower CXCR7 expression group and the higher expression group (P＜0.01). Conclusions The expression of CXCR7 protein is high in bladder cancer and the analysis of CXCR7 protein expression is potentially valuable in prognostic evaluation of bladder cancers. CXCR7 may play a role in the development of bladder urothelial cell cancer.     

The protective role of Smad7 in diabetic kidney disease: mechanism and therapeutic potential

OBJECTIVE

Although Smad3 has been considered as a downstream mediator of transforming growth factor-β (TGF-β) signaling in diabetes complications, the role of Smad7 in diabetes remains largely unclear. The current study tests the hypothesis that Smad7 may play a protective role and has therapeutic potential for diabetic kidney disease.

RESEARCH DESIGN AND METHODS

Protective role of Smad7 in diabetic kidney disease was examined in streptozotocin-induced diabetic mice that have Smad7 gene knockout (KO) and in diabetic rats given Smad7 gene transfer using an ultrasound-microbubble-mediated technique.

RESULTS

We found that mice deficient for Smad7 developed more severe diabetic kidney injury than wild-type mice as evidenced by a significant increase in microalbuminuria, renal fibrosis (collagen I, IV, and fibronectin), and renal inflammation (interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], intracellular adhesion molecule-1 [ICAM-1], and macrophages). Further studies revealed that enhanced renal fibrosis and inflammation in Smad7 KO mice with diabetes were associated with increased activation of both TGF-β/Smad2/3 and nuclear factor-κB (NF-κB) signaling pathways. To develop a therapeutic potential for diabetic kidney disease, Smad7 gene was transferred into the kidney in diabetic rats by an ultrasound-microbubble-mediated technique. Although overexpression of renal Smad7 had no effect on levels of blood glucose, it significantly attenuated the development of microalbuminuria, TGF-β/Smad3-mediated renal fibrosis such as collagen I and IV and fibronectin accumulation and NF-κB/p65-driven renal inflammation including IL-1β, TNF-α, MCP-1, and ICAM-1 expression and macrophage infiltration in diabetic rats.

CONCLUSIONS

Smad7 plays a protective role in diabetic renal injury. Overexpression of Smad7 may represent a novel therapy for the diabetic kidney complication.Diabetic nephropathy is a major complication of diabetes (1–4). Approximately 20–40% of patients with type 1 or type 2 diabetes mellitus (DM) develop diabetic nephropathy (5,6). Diabetic nephropathy is characterized by excessive deposition of extracellular matrix (ECM) proteins in the mesangium and tubulointerstitium, thickness of basement membrane of the glomeruli, and loss of podocytes with the development of microalbuminuria and a decline of renal function (2,3,7). Both in vivo and in vitro studies have demonstrated that renal fibrosis and inflammation play an important role in the pathogenesis of diabetic kidney disease (2–4,7–10). Transforming growth factor-β (TGF-β) family is a crucial mediator in the development of diabetic nephropathy (11–15).It is now clear that after binding to its receptors, TGF-β signals through two critical downstream mediators, Smad2 and Smad3, to exert its biological activities such as ECM production. In addition, TGF-β₁ also induces an inhibitory Smad called Smad7, which negatively regulates activation of Smad2/3 by TGF-β receptor competition and degradation via the ubiquitin-proteasome degradation mechanism (16,17). Recent studies have demonstrated that overexpression of Smad7 is capable of inhibiting renal fibrosis and inflammation by blocking the activation of both TGF-β/Smad and nuclear factor-κB (NF-κB) signaling pathway (18–22). In contrast, deletion of Smad7 promotes renal fibrosis and inflammation (23), suggesting that Smad7 may be a key regulator and a therapeutic agent for renal fibrosis and inflammation (24). Although it has been reported that Smad3 is pathogenic in fibrosis including diabetic kidney disease (25,26), the role of Smad7 in diabetes complications remains unexplored, and it is unknown whether blockade of the TGF-β signaling pathway by Smad7 has therapeutic potential for diabetes complications. Thus, in the current study, we uncovered the role of Smad7 in diabetic kidney disease induced in Smad7 knockout (KO) mice and developed new therapeutic strategy for diabetic kidney complication by targeting the TGF-β/Smad pathway with ultrasound-microbubble-mediated Smad7 gene therapy.     

不同海拔高度青少年最大氧供给和氧利用的特点及影响因素

目的探讨高原青少年最大氧耗量（ＶＯ２ｍａｘ）、最大氧供给量（ＤＯ２ｍａｘ）及氧利用的特点。方法对三个不同海拔高度（２２６０ｍ,３４１７ｍ,４３００ｍ）各１５例健康青少年的氧动力学指标进行测试。用自行车负荷递增法直接测定ＶＯ２ｍａｘ等气体交换指标;耳氧仪同步记录氧饱和度（ＳＯ２）;心阻抗法测定最大心指数（ＣＩｍａｘ）。结果血红蛋白浓度（Ｈｂ）随海拔高度的升高而增大（Ｐ＜０．０５）;ＶＯ２ｍａｘ、ＤＯ２ｍａｘ、ＣＩｍａｘ和ＳＯ２均随海拔升高而下降（Ｐ＜０．０５）;三个海拔高度的最大氧摄取率（ＥＲＯ２）无明显变化;ＶＯ２ｍａｘ和ＤＯ２ｍａｘ在三个海拔高度及总体样本中均呈显著直线相关（ｒ＝０．７７、０．７１、０．７２、０．９８,Ｐ＜０．０５）。结论高原青少年ＶＯ２ｍａｘ降低的原因为ＤＯ２ｍａｘ不足,而非氧利用障碍;ＣＩｍａｘ和ＳＯ２的下降是ＤＯ２ｍａｘ不足的决定因素,同时也是ＶＯ２ｍａｘ降低的主要原因。     

Alfacalcidol treatment increases bone mass from anticatabolic and anabolic effects on cancellous and cortical bone in intact female rats

It has been reported that alfacalcidol had an anticatabolic and anabolic effect on bone in ovariectomized and aged male rat models, but this has not been tested on intact female rats. The current study was to determine the effects of alfacalcidol on cancellous and cortical bone in intact female rats with or without exercise. Seventy-four, 8.5-month-old, intact female rats were orally treated with 0, 0.005, 0.025, 0.05, or 0.1 microg/kg alfacalcidol alone or in combination with raised cage (RC) exercise for 3 months. In vivo peripheral quantitative computerized tomography (pQCT) of the proximal tibial metaphyses (PTM) and ex vivo histomorphometric analyses of the PTM and tibial shaft (TX) were performed. Only the 0.1 microg alfacalcidol/kg dose proved to be anabolic. pQCT analysis showed that this dose increased total and cortical bone mineral content and density and trabecular bone mineral density. Histomorphometrically, it induced an anabolic response by increased trabecular mass and microarchitecture from stimulated cancellous bone and bone bouton formations, and suppressed bone resorption more than bone formation on the trabecular and endocortical surfaces, to produce a positive bone balance. A positive correlation between trabecular connectivity and bone bouton numbers occurred. These findings suggest alfacalcidol treatment augments bone mass by increased cancellous bone mass and improved trabecular architecture through its anticatabolic and anabolic properties in the intact adult female rat. Last, raised cage exercise alone or the combination of raised cage and alfacalcidol was no more effective than alfacalcidol alone.     

小主动脉瓣环患者机械瓣置换术后中期疗效分析

目的观察小主动脉瓣环患者行心瓣膜置换术后中期疗效和心功能恢复情况，探讨小口径瓣膜的使用范围。方法1990年7月至2003年6月共对62例患者施行19号主动脉机械瓣膜置换术（19mm瓣膜组），同时选择62例同期置换21号以上机械瓣膜患者做对照（21mm瓣膜组）；术后随访两组患者的临床症状、体征，心电图、超声心动图等指标，采用Kaplan—Meier分析生存曲线计算两组患者的生存率，并进行比较分析。结果19mm瓣膜组中有38例主动脉瓣区仍存在Ⅱ级以上杂音，心电图检查18例有ST段改变，术后11例仍存在胸闷、胸痛症状，术后心功能Ⅱ级33例，Ⅲ级29例；21mm瓣膜组术后心电图检查6例有ST段改变，术后3例有胸闷症状，偶尔有胸痛不适6例，术后心功能Ⅱ级48例，Ⅲ级14例，两组间比较差异有统计学意义（P=0．020）。两组患者术后左心室舒张期末内径、左心室后壁厚度、左心室重量指数、主动脉跨瓣压差等均较术前明显改善（P〈0．05），左心室射血分数（LVEF）术后5年与术前比较明显提高（P〈0．05），但两组间比较差异无统计学意义（P〉0．05）。19mm瓣膜组术后1年、5年生存率分别为93．5％、74．2％；21mm瓣膜组术后1年、5年生存率分别为95．2％、79．0％，两组间比较差异无统计学意义（P=0．231，0．110）。结论小口径主动脉瓣置换术能取得良好的效果和中期生存率。     

旋转臂自锁式髓内钉治疗股骨干骨折

目的 探讨旋转臂自锁式髓内钉(RBSN)治疗股骨干骨折的临床效果.方法 对32例股骨干骨折采用切开复位RBSN内固定.结果 患者均获随访,时间10～30(16.2±1.4)个月.全部骨性愈合,时间为12～26(21.3±2.1)周.采用HSS膝关节评分标准评价疗效:优30例,良1例,可1例,优良率96.9%.结论 RBSN治疗股骨干骨折创伤小,操作简便,固定牢固,疗效确切.     

肝移植术后肺部真菌感染的诊断和治疗

目的探讨肝移植术后肺部真菌感染的早期诊断及治疗方法。方法回顾分析20例肝移植术后肺部真菌感染患者的临床资料,分析其原发病、免疫状态、感染真菌的种类及抗真菌药物的应用。结果20例患者念珠菌感染17例,死亡2例,曲霉菌感染3例,死亡2例。氟康唑、伊曲康唑、两性霉素B治疗有效率70％,伏立康唑、卡泊芬净治疗有效率100％。结论肝移植术后真菌感染高发,以危重患者为主要目标人群,发生早,病情重。诊断分三级,达到临床诊断即应及早治疗。治疗以伏立康唑为首选,严重感染者联合应用卡泊芬净效果良好。     

应用医用电子去脂机行颈部脂肪抽吸临床效果观察

目的：探讨医用电子去脂机行颈部脂肪抽吸的临床效果以及安全性。方法：共收治就医者87例，按其要求分别对颈前区、颈项部等进行电子去脂术，针对每位就医者手术治疗前后颈围测量及照片的对比，进行临床效果的评估。结果：全部病例均取得了明显的治疗效果，术后无反弹，术中损伤小，就医者无明显痛苦，手术无并发症发生。结论：应用医用电子去脂机行颈部脂肪抽吸，操作简单，安全可靠，治疗效果显著，就医者易接受。     

超声引导微通道经皮肾镜下碎石术的应用研究(附896例报告)

目的:探讨超声引导下行微通道经皮肾镜下碎石术(mini-PNL)治疗上尿路结石的可行性和优越性.方法:超声引导下行mini-PNL术共896例,其中肾鹿角形结石396例,肾盂结石350例,输尿管上端结石143例,移植肾结石7例.结果:896例患者中146例(16.3%)术前超声评估患肾积水较轻,而穿刺前输尿管插管,注生理盐水形成人工肾积水便于穿刺.872例(97.3%)患者1次穿刺成功,其余24例(2.7%)于一周后经第2次穿刺,22例成功,2例改行X线定位穿刺成功;碎石术中B超发现345例(38.5%)存在＞5 mm结石,在超声引导下定位并粉碎.术后每两周超声随访,1个月后,896例患者中823例(91.8%)结石完全清除,73例(8.2%)有残余小结石.并发症包括发热111例(12.3%),其中8例高热伴发菌血症败血症;出血138例(15.4%),其中2例发生下腔静脉损伤,但无严重出血发生;胸腔积液3例(0.3%);无腹腔内脏器损伤发生.结论:超声能对拟行mini-PNL术的病例作出准确判断,指导术前准备;术中超声引导可提高穿刺成功率,并有效避免血管及脏器损伤,避免大结石残留;术后可正确评估手术疗效.超声引导mini-PNL术治疗上尿路结石安全可行,适合在基层医院推广应用.     

Lichtenstein法无张力疝修补术治疗120例成人腹股沟疝体会

目的总结Lichtenstein法治疗成人腹股沟疝的疗效。方法120例腹股沟疝患者,采用Lichtenstein法行无张力疝修补术,其中斜疝93例（包括复发性斜疝14例,双侧斜疝3例）;直疝27例。结果120例患者手术过程顺利,手术时间平均50（45-60）min,术后住院5-7 d。伤口感染1例,经抗生素治疗及局部换药痊愈;阴囊积液4例,经阴囊穿刺1-2次治愈;局部疼痛2例,术后1-3月逐渐好转。术后96例获随访,平均14个月,无一例复发。结论Lichtenstein法治疗成人腹股沟疝效果确切,符合解剖生理特点,操作简单,术后并发症少,值得推广。