The xeroderma pigmentosum complementation group C gene (XPC) has been identified as important for repairing UV-related DNA damage. Some subtle changes in this gene may impair repair efficiency and influence susceptibility to human cancers, including skin cancer. Two polymorphisms in XPC, 939A>C (rs2228001) and 499C>T (rs2228000), are considered to have possible associations with the risk of skin cancer, but the reported results have been inconsistent. Here we performed a meta-analysis of the available evidence regarding the relationship between these two polymorphisms and the risk of skin cancer. All relevant studies were searched using PubMed, Embase and Web of Science before February 2012. A total of 8 case-control studies were included in this analysis, and no convincing associations between the two polymorphisms and risk of skin cancer were observed in any of the genetic models. Stratified analyses by skin cancer type also did not detect significant associations in any subgroup. This meta-analysis suggested that the XPC 939A>C and 499C>T polymorphisms may have little involvement in susceptibility to skin cancer.

<正>患者男,78岁。火焰烧伤面部、腹部和四肢4h入院。既往无尿崩症病史。查体:神志清,烦躁,脉搏90次/min,呼吸24次/min,血压150/80mmHg。创面主要位于双下肢。入院诊断:(1)烧伤(火焰)50%,深Ⅱ度20%面、腹、四肢,Ⅲ度30%双下肢。(2)轻度吸入性损伤。入院后行简单清创,常规静脉快速补液抗休克,入院后第1小时补液500ml,尿量550ml;第2小时补

目的:探讨负压封闭引流(VSD)技术在治疗电烧伤创面中的应用效果。方法:对20例创面应用负压引流技术,待肉芽组织新鲜后,行植皮或植皮联合皮瓣转移术。结果:术后5～7d引流后揭除敷料,创面无感染迹象,肉芽新鲜,12例行自体皮移植后创面愈合;5例行植皮联合皮瓣移植后创面愈合;3例再次VSD负压引流术后行植皮后创面愈合。结论:负压封闭引流技术治疗电烧伤创面,可控制感染,改善创面条件,促进创面愈合,疗效可靠。

Mammalian target of rapamycin (mTOR) is an important mediator for cross talk between nutritional signals and metabolic signals of insulin by downregulating insulin receptor substrate proteins. Therefore, mTOR inhibition could become a therapeutic strategy in insulin-resistant states, including insulin resistance induced by burn. We tested this hypothesis in the rat model of 30% TBSA full thickness burn, using the mTOR inhibitor rapamycin. Rapamycin (0.4 mg/kg, i.p.) was injected 2 h before euglycemic–hyperinsulinemic glucose clamps at 4 days after burn. IRS-1, phospho-serine307, phospho-tyrosine of IRS-1 and phospho-mTOR in muscle tissue were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Plasma TNF-α, insulin and C-peptide were determined before and after euglycemic–hyperinsulinemic glucose clamps. Our data showed that TNF-α, insulin and C-peptide significantly increased in the early stage after burn (P < 0.01). The infused rates of total 10% glucose (GIR, mg/kg min) significantly decreased at 4 days after burn. The level of IRS-1 serine307 phosphorylation in muscle in vivo significantly increased after burn (P < 0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P < 0.01). Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine307 phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. However, TNF-α, insulin and C-peptide were not decreased by rapamycin treatment postburn. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose metabolism, and at least, partly contributes to burn-induced insulin resistance. mTOR inhibition may become a therapeutic strategy in insulin-resistant states after burn.

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. Early excision and grafting reduces cytokines and insulin resistance in burned rats. The authors hypothesized that early wound excision and grafting in patients would also reduce insulin resistance induced by major burn. Thirty-five adult surviving major burn patients (>40%TBSA burn) were recruited. The removal of dead devitalized tissue and allografting in escharectomy group was performed within 72 hours and in control group about 7 days after burn injury. The concentrations of plasma insulin, glucose, and cytokines were measured at 2 and 5 days postburn. Euglycemic-hyperinsulinemic glucose clamps were performed at 5 days after burn. The levels of phosphotyrosine, phosphoserine³¹² of insulin receptor substrate (IRS)-1, and phospho-jun N-terminal kinase (JNK) in muscle were analyzed with immunoprecipitation and Western blotting at 5 days postburn. Escharectomy and allografting during shock stage significantly reduced the levels of interleukin-6 and tumor necrosis factor-α, decreased the levels of phosphoserine³¹² and phospho-JNK, increased the level of phosphotyrosine of IRS-1, and further reduced insulin resistance at 5 days after thermal injury compared with delayed excision group. Escharectomy and allografting during shock stage seemed to have an immunomodulatory effect on the inflammatory mediators and further to reduce insulin resistance induced by major burns in patients by decreasing the phosphorylation of IRS-1 serine³¹² and JNK1/2.

<正>大面积烧伤患者在创面愈合后,后期的功能恢复成为治疗的重要环节,但许多患者存在着一个共性问题,即自体皮源的严重匮乏。很多患者只有头皮是正常的,但在烧伤早期的创面修复中已多次被取过,后期整形时功能部位的瘢痕切除需要移植较厚的皮片,而且需要手术的部位多,需要的自体皮也多,面对这种自体皮源少,又很难取到较厚皮片的矛盾,笔者采用了

Burn wound excision and grafting is a common clinical practice that decreases patient morbidity and mortality. It is not known, however, if the salutary effects of this procedure are related to effects on interleukin 6 (IL-6) and tumor necrosis factor (TNF-) alpha, and to reducing insulin resistance after burn. Sprague-Dawley rats were randomly divided into three groups: control, burn, burn +/- excision groups. Rats in burn group were given a third-degree scald burn covering 30% total body surface area (TBSA) and no wound excision. Rats in burn +/- excision group were subjected to a 30% third-degree burn followed by complete excision and allografting of the injury site within 15 min after burn. The rats in control group were treated in the same manner as the burn group, except that they were immersed in a room-temperature water. Glucose tolerance tests (GTT) were observed at 3 days after burn, euglycemic-hyperinsulinemic glucose clamps were performed at 4 days after burn and interleukin 6 (IL-6) and tumor necrosis factor (TNF-) alpha were determined after euglycemic-hyperinsulinemic glucose clamps. The levels of IL-6 and TNF-alpha increased after burn. Significant differences in GTT were observed between control and burn groups, and the rate of glucose infused measured in burned rats was significantly decreased compared with that in control at 4 days after burn. Early excision and grafting significantly decreased levels of IL-6 and TNF-alpha, and further reduced insulin resistance following thermal injury compared with burn group. Conclusion: Early excision and grafting appeared to have an effect on inflammatory mediators and further reduced insulin resistance induced by major burns. (C) 2010 Elsevier Ltd and ISBI. All rights reserved.

OBJECTIVE:To investigate the role of c-Jun NH (2)-terminal kinase (JNk) in insulin resistance after burn and its mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomized to control, burn and burn + anisomycin groups. The rats in control group received sham burn trauma, and burn and burn + anisomycin groups received 30% total body surface area (TBSA) full thickness burn injury. Anisomycin (5 mg/kg) together with 250 microl dimethyl sulfoxide (DMSO) was injected to the rats in anisomycin group intravenously, and only 250 microl DMSO in the other two groups. Euglycemic-hyperinsulinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phospho-tyrosine of insulin receptor substrate (IRS)-1 and phospho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups.RESULTS:The infusing rates of total 10% glucose (mg x kg(-1) x min(-1)) in control, burn and burn + anisomycin group were 12.3 +/- 0.4, 6.6 +/- 0.3, 6.5 +/- 0.4, respectively. The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn.CONCLUSIONS:The activation of JNK elevates the level of IRS-1 phospho-serine 307 and might play a role in insulin resistance after burn in rats.

OBJECTIVE To investigate the role and mechanism of c-Jun N-terminal kinase (JNk) inhibitor (SP600125) in amelioration of insulin resistance after scald. METHODS Twenty-four Sprague-Dawley rats were randomized into sham (the process of scald was mimicked by water at room temperature) , scald, scald and SP600125 groups. The rats were inflicted with 30% TBSA full-thickness scald in the latter two groups. Euglycemic-hyperinsulinemic glucose clamp experiment was carried out 4 days after scald. SP600125 was administered to the rats in scald and SP600125 2 hrs before Euglycemic-hyperinsulinemic glucose clamp was performed. Changes in the phospho-Serine307 and phospho-tyrosine of IRS-1 activity, as well as expression of phospho-JNK in muscles were determined. RESULTS Euglycemic-Hyperinsulinemic Glucose Clamps experiment showed that the infusion rate of 100 g/L glucose in sham, scald, scald and SP600125 groups were (12. 33 +/-0. 42) , (6. 61 +/-0. 27) , (11. 11 +/-0. 68) mgx kg(-1) x min(-1) , respectively ( P <0.01). The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles were significantly increased, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after scald. Compared with scald group, the level of IRS-1 Serine307 phosphorylation and JNK activity in scald and SP600125 group were decreased but tyrosine phosphorylation was elevated. CONCLUSION SP600125 can partially ameliorate insulin resistance after scald by inhibition of JNK activation, and decrease the level of IRS-1 phospho-serine307.

改善微循环、减轻缺血再灌注损伤是治疗烧伤后休克的目的,但如何判断微循环的状况,掌握补液尺度是临床工作的难点和关键.常用监测指标如心率、血压、尿量在原理上均不能直接反映组织灌流及氧输送情况,且受神经、体液调节及利尿剂、血管活性药物、脏器功能、个体差异等因素影响较大,延迟复苏和病程特殊的重度休克,情况更为复杂.

PS can stimulate immune responses of anti-HBs and anti-preS2 in normal and transgenic mice. The appearance of anti-preS2 was 1-2 weeks earlier than that of anti-HBs. HBsAg and HBeAg in sera turned negative 8 weeks after immunization. At the 8th week, hepatocytes showed extensive granular degeneration and hydropic degeneration. There was no obvious difference in the amount of mononuclear lymphocytes between pre- and post-gene immunization. It is showed that specific humoral immune response can be effectively induced by PS after DNA-based immunization, and PS seems to be responsible for the disapearance of HBsAg and HBeAg in sera of HBV transgenic mice. The results provide an evidence for further investigation of genetic vaccine in the treatment of chronic HBV infection.

Objective:To investigate the effects of sirolimus on IRS-1 phospho-Ser 307 and insulin resistance after burn in rats. Methods: Twenty-four Sprague-Dawley rats were randomized into control(sham burn trauma),burn(30%TBSA full thickness burn injury) and burn+sirolimus groups(n=8). Euglycemic-hyperinsulinemic glucose clamp was performed 4 d after burn. Sirolimus (0.4 mg/kg) was injected intraperitoneally 2 h before euglycemic-hyperinsulinemic glucose clamps. PhosphoSerine 307 ,phosphotyrosine of IRS-1 and phospho-mTOR in muscles and fat tissues were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Results: The infused rates of total 10% glucose (GIR, mg/kg·min) in control,burn and burn+sirolimus groups were 12.33±0.42,6.61±0.27 and 10.35±0.63,respectively (P0.01). The level of IRS-1 Serine 307 phosphorylation in both muscle and fat tissues in vivo increased significantly,while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn. Sirolimus inhibited the activation of mTOR,reduced Serine 307 phosphorylation,elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. Conclusion: Sirolimus inhibits the activation of mTOR,decreases the level of IRS-1 phosphoserine 307 , and, at least partly,ameliorates insulin resistance after burn.

目的:观察烧伤后胰岛素受体底物1(IRS-1)及其丝氨酸307和酪氨酸磷酸化的变化,探讨烧伤后胰岛素抵抗的分子机制.方法:6周龄SD大鼠(体质量160～170g)随机分为假烫伤组(n=8)和烫伤组(n=8),烫伤组大鼠制成烧伤面积为30%的Ⅲ度烫伤模型,伤后第4天,禁食5 h后的大鼠,进行正常血糖高胰岛素钳夹技术实验,实验后颈动脉放血处死,立即采集肌肉和脂肪标本,采用免疫沉淀和免疫印迹方法分析IRS-1及其丝氨酸307和酪氨酸磷酸化的变化情况.结果:烫伤后肌肉和脂肪组织中IRS-1上丝氨酸307磷酸化水平显著升高[假烫伤组光密度值设定为1,进行对照比较;骨骼肌:(3.78±1.58)vs(1.00±0.16),P＜0.01;脂肪组织:(2.09±0.44)vs(1.00±0.18),P＜0.05],而IRS-1上酪氨酸磷酸化水平显著降低[骨骼肌:(0.66±0.32)vs(1.00±0.34),P＜0.05;脂肪组织:(0.62±0.27)vs(1.00±0.24),P＜0.05].烫伤后IRS-1含量无显著性改变[肌肉组织:(0.87±0.05)vs(1.00±0.17),P＞0.05;脂肪组织:(0.93±0.01)vs(1.00±0.16),P＞0.05].结论:烧伤后IRS-1丝氨酸307磷酸化升高和酪氨酸磷酸化降低可能是烧伤后胰岛素抵抗发生的重要分子机制之一.

Aims: Burn injury is associated with insulin resistance. The exact molecular mechanism of insulin resistance after bum has not been elucidated. The aim of this study was to investigate the changes of IRS-1, Ser307 and tyrosine phosphorylation of IRS-1 after bum. Methods. Sprague-Dawley rats received 30% TBSA full thickness bum injury or sham bum trauma. Euglycemic-hyperinsulinemic glucose clamp was performed at the 4th day after the bum. IRS-1, phospho-Ser307 and phospho-tyrosine of IRS-1 were determined by immunoprecipitation and Western blot analysis. Results. Our data showed that the infused rate of total 10% glucose (mg/kg/min) in the Burn group decreased significantly compared with that in the Control group (6.74±20 vs 12.14±0.30; p<0.01). The level of IRS-1 Ser307 phosphorylation increased significantly in the Bum group compared with that in the Control group (p<0.01), whereas insulin-induced tyrosine phosphorylation of IRS-1 decreased significantly in the Bum group in comparison with that in the Control group (P<0.05). Quantities of IRS-1 were not significantly different between two groups. Conclusions. This study indicates Ser307 hyper-phosphorylation and tyrosine hypo-phosphorylation of IRS-1 in vivo, and these may play role in the molecular mechanism of insulin resistance after bum.

OBJECTIVE:To study the changes in plasma sodium level and blood erythrocyte after resuscitation with different fluid regimes at early postburn stage. METHODS:One hundred and fifty burn patients admitted to our burn ward were randomly divided into three groups based on the different regimes of fluid resuscitation, i.e. A (n = 50, resuscitation with balanced salt solution for to the patients with middle and small burn area, Na(+) = 130 mmol/L); B (n = 50, with the same regime as in group A for those with large burn area), and C (n = 50, with hypertonic saline resuscitation for those with large burn area, Na(+) = 174 mmol/L) groups. The fluid supplementation, and changes in plasma sodium level and blood erythrocyte count, and the mean corpuscular volume (MCV) were observed during 1st to 3rd post burn day (PBD). RESULTS:The average volume of fluid supplementation in C group was lower than that in A and B groups (P < 0.01), though the average sodium supplementation in C group was higher than that in B group within 3 PBDs (P < 0.01). The average plasma level of sodium in B group was obviously lower than that in C group within 3 PBDs (P < 0.05). Negative correlation between the plasma sodium level and burn index (BI) was observed in A and B group on 1 PBD (r = -0.84, P < 0.01). The plasma sodium level was in the lower margin of normal range (137.4 +/- 3.9) mmol/L in B group, while that in C group was in the higher margin of normal range with obvious difference compared with B and C groups (P < 0.05 or 0.01). The MCV in group was lower than that in B group on the 1st and 2nd PBD, i.e. (92.1 +/- 4.5) fl vs (95.5 +/- 5.5) fl on the 1st PBD, and (90.9 +/- 5.4) fl vs (93.2 +/- 6.4) fl on the 2nd PBD, P > 0.05). CONCLUSION:The plasma sodium level was stable with milder degree of swelling of the erythrocytes when hypertonic saline resuscitation was given to patients with large burn area during early postburn stage.

Objective To investigate the prevention methods and management of visceral complications in severely burned shipman patients.Methods A retrospective review was undertaken to analyze the incidence and management of visceral complications in 31 severely burned shipman patients who were admitted to our center during the period from February 1997 to May 2000.Thirty-two male-,age-,TBSA- and full thickness-matched non-shipman burned patients were selected randomly to form the control group.Results The incidence of ARDS,stress ulcer bleeding and hepatic failure in shipman burned patients was 32.3%,19.4% and 38.7% respectively,all of which were significantly higher than those in the non-shipman burned patients.Comprehensive measures emphasizing on prior prevention were utilized to deal with the visceral complications.30 were cured and 1 died in the shipman patient group,while all 32 non-shipman patients were cured.There was no significant difference in the survival rate between the two groups.Conclusions Although there was a higher incidence of visceral complications,a satisfactory outcome of the burned shipman patients can be achieved with the comprehensive measures emphasizing on prior prevention undertaken.