酸性成纤维细胞生长因子治疗深Ⅱ度烧伤的多中心随机对照临床试验

目的:评价重组人酸性成纤维细胞生长因子(rh-a FGF)与重组人碱性成纤维细胞生长因子(rh-b FGF)治疗深Ⅱ度烧伤的临床疗效与安全性。方法:采用多中心、随机、平行对照临床试验方法,入选5个研究中心216例深Ⅱ度烧伤患者,两组患者均给予相应抗感染、营养补充治疗。观察组(108例)入院时首先根据创面大小给予rh-a FGF1瓶/5 cm2进行冲洗,然后每日3~4喷/cm2喷雾治疗,6~8次/d,对照组(108例)给予rh-b FGF治疗,给药方法同观察组。随访30 d后,评价两组患者创面愈合情况。结果:观察组完全愈合时间、溶痂时间、12 d完全愈合率、15 d完全愈合率等指标均明显优于对照组(P<0.05)。治疗7 d后,观察组白细胞水平、渗出评分均明显低于对照组(P<0.01)。两组总评分中度构成比比较,差异有统计学意义(P<0.05)。结论:rh-a FGF治疗深Ⅱ度烧伤创面临床疗效优于rh-b FGF,安全性相似。     

大花紫玉盘中新多氧取代环己烯类的结构鉴定

从番荔枝科紫玉盘属植物大花紫玉盘( Uvaria grandiflora Roxb.)根茎中分得4种新的多氧取代环己烯及已知化合物zeylenol,应用波谱分析、X-射线衍射、园二色谱和 Mosher 酯制备等手段确定了全部新化合物的结构及其绝对构型,分别命名为大花紫玉盘醇A(1),B(2),E(3)和F(4)。     

TNF-α对大鼠Leydig细胞的作用及机制研究

目的观察TNF-α对睾丸细胞功能的影响并探讨其可能机制。方法通过Percoll不连续密度梯度分离获取大鼠Leydig细胞进行原代培养。HE染色进行细胞形态学观察。Leydig细胞培养48h后在培养液中分别加入不同浓度的大鼠TNF-α,使其终浓度达到0.1、1、10、100ng/ml,分别在培养的第1、2、3、4天取上清,通过放免法测定上清液中睾酮的含量,应用MTT法测定细胞增殖情况,流式细胞术与丫啶橙(AO)染色检测及观察Leydig细胞凋亡情况。结果原代细胞通过提纯后的细胞纯度可达70%~80%。HE染色后可见细胞胞质含量丰富,含有分泌颗粒,胞核圆。TNF-α在0.1~100ng/ml浓度范围内能呈剂量依赖的方式抑制Leydig细胞睾酮的基础分泌。0.1、1、10、100ng/mlTNF-α作用24h后,对Leydig细胞睾酮分泌量的抑制率分别为22.03%、34.98%、52.95%、74.83%。各组Leydig细胞睾酮的分泌量随时间延长呈减少的趋势,但除100ng/ml组外,其他各组各时间点比较差异无统计学意义。高浓度TNF-α(10、100ng/ml)组具有抑制Leydig细胞增殖和促进其凋亡作用,其增殖抑制率分别达到38.35%±4.17%、76.35%±8.65%,而凋亡率分别为13.23%±1.11%、26.43%±5.82%,与对照组比较有统计学意义(P<0.01)。AO染色见高浓度TNF-α(10、100ng/ml)组出现明显的细胞凋亡。结论TNF-α对Leydig细胞睾酮的基础分泌具有抑制作用,在较高浓度时该作用可能与其抑制Leydig细胞增殖并促进细胞凋亡有相关。     

A review of the safety and clinical utility of contrast echocardiography

There are limitations to the sensitivity and specificity of conventional two-dimensional echocardiograms in making an accurate diagnosis in certain patient populations. This led to the development of specific contrast-enhancing agents with the following characteristics: small enough to cross the pulmonary capillary bed, remain stable throughout the length of the procedure, do not dissolve in blood, and rapidly cleared from the body with low toxicity. Unfortunately, the use of contrast echocardiography has not taken off as expected. The low take-up rate among clinicians can largely be attributed to the black box warning by the United States Food and Drug Administration in 2007, after the coincidental occurrence of four patient deaths and about 190 severe cardiopulmonary reactions shortly after contrast agent administration. In this article, we address the clinical safety of contrast agents, share our institution’s experience in using it and elaborate on the clinical indications of contrast echocardiography.     

The role of the basolateral amygdala in stimulus-reward memory and extinction memory consolidation and in subsequent conditioned cued reinstatement of cocaine seeking

The consolidation of cue-cocaine associations and extinction learning (i.e. cue-no cocaine associations) into long-term memory probably regulates the long-lasting control of conditioned stimuli (CS) over cocaine-seeking behaviour, and the basolateral amygdala (BLA) may play a role in this phenomenon. To test this hypothesis, rats previously trained to self-administer cocaine underwent a single classical conditioning (CC) session, during which they received passive pairings of cocaine infusions and a novel light + tone stimulus complex. After additional self-administration sessions in the absence of CS presentation and subsequent extinction training sessions, the ability of the CS to reinstate cocaine-seeking on five test days was assessed. Rats received intra-BLA microinfusions of vehicle or the Na+-channel blocker tetrodotoxin (TTX) immediately after CC (consolidation of CS-cocaine associations) or immediately after reinstatement testing (consolidation of extinction learning). TTX administered immediately after CC attenuated subsequent CS-induced reinstatement. In contrast, TTX administered after the first reinstatement test impaired the extinction of cocaine-seeking behaviour during a second reinstatement test by disrupting extinction memory. Overall, these findings suggest that Na+ channel-mediated mechanisms within the BLA mediate the consolidation of both cocaine-stimulus association and extinction learning, two processes that have opposite effects on subsequent cue-induced cocaine-seeking behaviour.     

胰岛素对烫伤血清诱导骨骼肌成肌细胞凋亡的调控作用

目的 探讨胰岛素对烫伤大鼠血清诱导大鼠骨骼肌成肌细胞株L6凋亡的调控作用及机制.方法 体外培养L6细胞,按照随机数字表法分为对照组、烫伤血清组、胰岛素组和烫伤血清+胰岛素组.在上述4组细胞培养液中分别添加体积分数20％正常大鼠血清、体积分数20％烫伤大鼠血清、体积分数20％正常大鼠血清+100 nmol/L胰岛素、体积分数20％烫伤大鼠血清+100 nmol/L胰岛素,孵育48 h.行Hoechst 33258染色,于倒置荧光显微镜下观察细胞凋亡形态并计数凋亡细胞;行膜联蛋白V-异硫氰酸荧光素/碘化丙啶双标记染色,用流式细胞仪检测细胞凋亡率;蛋白质印迹法检测细胞磷酸化(p一)蛋白激酶B(Akt)、p-磷脂酰肌醇3激酶(PI3K)、Bax、Bcl-2、活化半胱氨酸天冬氨酸蛋白酶3( caspase-3)的蛋白表达量.对实验数据行组间或配对t检验.结果 (1)倒置荧光显微镜下可见,烫伤血清组凋亡细胞为每视野(59.6±3 9)个,显著多于对照组、胰岛素组、烫伤血清+胰岛素组[每视野(4 9±2.6)、(5 5±2 1)、(19.7±2 3)个,t值分别为28.53、29.86、21.53,P值均小于0.01].(2)流式细胞仪检测结果显示,烫伤血清组细胞凋亡率为(18.5±1.8)％,明显高于对照组、胰岛素组及烫伤血清+胰岛素组[(1.1±0 6)％、(1 5±0 3)％、(7.8±0.6)％,t值分别为22.41、22 83、13 92,P值均小于0 01].(3)蛋白质印迹检测显示,烫伤血清组Bax蛋白表达量(1.12±0.63)及活化caspase-3蛋白表达量(2.15±0.51)明显高于对照组(0.16±0 03、0.21±0.03,t值分别为3 80、10 69,P值均小于0 01),p-Akt蛋白表达量(0.20±0.03)明显低于对照组(0 42±0 07,t=-8.46,P＜0.01);Bcl-2及p-PI3K蛋白表达量(0.19±0 03、0.17±0.03)与对照组(0.26±0 09、0 28±0.07)接近(t值分别为-2.73、-1.14,P值均大于0 05).与烫伤血清组比较,烫伤血清+胰岛素组Bax蛋白表达量(0.40±0.14)和活化caspase-3蛋白表达量(0.83±0.18)明显降低(t=-3.23,P ＜0.05;t =6.66,P ＜0.01),Bcl-2、p-Akt及p-PI3K蛋白表达量均升高(0.39±0.10、0 78±0 03、0.47±0.12,t值分别为4.07、18.71、5 05,P＜0.05或P＜0.01).结论 烫伤大鼠血清可显著促进骨骼肌成肌细胞凋亡,胰岛素能通过PI3K/Akt信号途径抑制细胞凋亡.     

Angiotensin II receptors modulate muscle microvascular and metabolic responses to insulin in vivo

OBJECTIVE

Angiotensin (ANG) II interacts with insulin-signaling pathways to regulate insulin sensitivity. The type 1 (AT₁R) and type 2 (AT₂R) receptors reciprocally regulate basal perfusion of muscle microvasculature. Unopposed AT₂R activity increases muscle microvascular blood volume (MBV) and glucose extraction, whereas unopposed AT₁R activity decreases both. The current study examined whether ANG II receptors modulate muscle insulin delivery and sensitivity.

RESEARCH DESIGN AND METHODS

Overnight-fasted rats were studied. In protocol 1, rats received a 2-h infusion of saline, insulin (3 mU/kg/min), insulin plus PD123319 (AT₂R blocker), or insulin plus losartan (AT₁R blocker, intravenously). Muscle MBV, microvascular flow velocity, and microvascular blood flow (MBF) were determined. In protocol 2, rats received ¹²⁵I-insulin with or without PD123319, and muscle insulin uptake was determined.

RESULTS

Insulin significantly increased muscle MBV and MBF. AT₂R blockade abolished insulin-mediated increases in muscle MBV and MBF and decreased insulin-stimulated glucose disposal by ~30%. In contrast, losartan plus insulin increased muscle MBV by two- to threefold without further increasing insulin-stimulated glucose disposal. Plasma nitric oxide increased by >50% with insulin and insulin plus losartan but not with insulin plus PD123319. PD123319 markedly decreased muscle insulin uptake and insulin-stimulated Akt phosphorylation.

CONCLUSIONS

We conclude that both AT₁Rs and AT₂Rs regulate insulin’s microvascular and metabolic action in muscle. Although AT₁R activity restrains muscle metabolic responses to insulin via decreased microvascular recruitment and insulin delivery, AT₂R activity is required for normal microvascular responses to insulin. Thus, pharmacologic manipulation aimed at increasing the AT₂R-to-AT₁R activity ratio may afford the potential to improve muscle insulin sensitivity and glucose metabolism.Skeletal muscle microvascular perfusion distribution is determined by precapillary terminal arteriolar tone. Dilating these arterioles increases microvascular perfusion and expands the capillary exchange surface area, whereas constriction leads to the opposite (1,2). Microvascular insulin resistance and dysfunction are closely related with metabolic insulin resistance in diabetes (2–4). Insulin-mediated microvascular recruitment precedes insulin-stimulated glucose uptake in skeletal muscle (5), and blockade of insulin’s microvascular action with N^ω-nitro-l-arginine methyl ester (l-NAME) decreases steady-state insulin-stimulated glucose disposal by ~40% (5,6).To act on muscle, insulin must first traverse the microvasculature perfusing the muscle and then be transported through the vascular endothelium into muscle interstitium. Recent evidence suggests that altered muscle microvascular perfusion profoundly affects insulin delivery and action in muscle (2). Many physiological factors regulate muscle microvascular perfusion in vivo, including insulin, mixed meals, and muscle contraction (7–12). Increased muscle microvascular recruitment induced by muscle contraction is associated with increased muscle insulin uptake (11).The renin-angiotensin system (RAS) plays a central role in maintaining hemodynamic stability (13,14), and angiotensin (ANG) II can interact with the insulin-signaling pathways to regulate insulin sensitivity. In cultured cells, ANG II acts via the ANG II type 1 receptor (AT₁R) to impair insulin actions (15–17). On the other hand, acutely raising ANG II systemically improves insulin-stimulated muscle glucose utilization in humans (18–20) and increases muscle microvascular recruitment independent of blood pressure changes in rodents (21). Both the AT₁R and ANG II type 2 receptor (AT₂R) are present on endothelial cells, vascular smooth-muscle cells, and other vessel-associated cells throughout skeletal muscle microcirculation (13,22,23). ANG II stimulates cell proliferation and vasoconstriction via the AT₁Rs and promotes vasodilation through the AT₂R (24,25). We recently have reported that both the AT₁Rs and the AT₂Rs significantly regulate basal microvascular tone and glucose use by muscle (21). Although basal AT₂R activity increases muscle microvascular blood volume (MBV) (an index of microvascular surface area and perfusion) and glucose extraction, basal AT₁R activity decreases both (21).In the current study, we assessed whether ANG II receptors modulate muscle insulin delivery and sensitivity in vivo. Our results indicate that both AT₁Rs and AT₂Rs regulate insulin’s microvascular and metabolic action in muscle. Although AT₁R activity restrains muscle metabolic responses to insulin via decreased microvascular recruitment and insulin delivery, AT₂R activity is required for normal microvascular responses to insulin.     

Reconstruction of fronto-orbital and nasal defects with compound epoxied maleic acrylate/hydroxyapatite implant prefabricated with a computer design program

The repair of fronto-orbital nasal bone defects may be a troublesome problem to plastic surgeons. This report aims to present the results of reconstruction of fronto-orbital nasal bone defects with the prefabrication of epoxied maleic acrylate/hydroxyapatite compound (EH compound) using 3-dimensional (3D) imaging data and computer-assisted manufacturing techniques, sometimes combined with autogenous bone to repair nasal defect. Helical computed tomography data were used to create a 3D model of the patient's skull. On the basis of these data, the individual shape of the implant was created by a computer-aided design/computer-aided manufacturing program. A rapid prototyping system was applied for production of the physical models. A total of 12 patients with traumatic fronto-orbital nasal defects were included in this study. The patients followed up for 1 to 24 months. The satisfactory results, such as excellent symmetry, stability, and normal fronto-orbital contours were obtained for all patients. The operating time was short without any complications. The depression of the region of fronto-orbital nasal bone defects always achieved an attractive or satisfactory prominence that was in balance and harmony with other facial features of all the patients. This method allows accurate fabrication of the implant. It improves the surgical techniques and reduces the risk of a second intervention, with improved aesthetic outcomes.     

螺旋CT胆系成像的临床应用

目的：探讨螺旋ＣＴ胆系成像（ＳＣＴＣ）技术,并对其临床应用价值做一评估。方法：采用５０％ 胆影葡胺２０～４０ ｍ ｌ静脉缓注。３３ 例延时３０～６０ ｍ ｉｎ,１６例延时９０ ｍｉｎ 后行螺旋ＣＴ容积扫描,将图像数据传至工作站作三维、四维及ＭＰＲ成像。结果：我们用此法检查了４９ 例病人,其中２５例为胆囊结石,９例胆总管结石,胆囊术后胆总管狭窄２例,５例为胆管癌,正常者８ 例。结论：螺旋ＣＴ胆系成像是有效的无创伤性胆系成像技术,弥补了常规ＣＴ及螺旋ＣＴ平扫在胆系疾病诊断中的不足。     

CT引导下放射性粒子植入治疗肺转移癌

目的探讨种植放射性125I粒子治疗肺转移癌的近期疗效。方法82例126个肺转移灶在CT引导下经皮穿刺肿瘤内种植放射性125I粒子,处方剂量80Gy。6个月后复查CT观察肿瘤体积变化,随访2年。结果靶区瘤体接受的平均照射剂量(159.3±34.5)Gy,中位剂量(118.6±33.2)Gy。6个月后复查CT显示肿瘤完全缓解25.4%(32/126),部分缓解64.3%(81/126),无变化6.3%(8/126),进展4.0%(5/126),总有效率89.7%(113/126)。并发气胸12例,咳血痰41例。死亡病例:8~12个月11例,其中恶性纤维组织细胞瘤6例,肺癌3例,直肠癌1例,肝癌1例;13~24个月15例,其中恶性纤维组织细胞瘤4例,肺癌4例,卵巢癌4例,多发骨髓瘤2例,子宫平滑肌肉瘤1例。1年存活71例,存活率86.6%,2年存活56例,存活率68.3%。结论CT引导下经皮穿刺肿瘤内种植放射性125I粒子治疗肺转移癌的近期疗效肯定。