神经肽P物质在糖尿病足溃疡皮肤中的表达变化

目的 探讨神经肽P物质（SP）在糖尿病足溃疡（DFU）皮肤中的表达变化. 方法 免疫组织化学法观察对照（Con）、非糖尿病DFU（NDFU）组和DFU组皮肤组织中SP及增殖细胞核抗原（PC-NA）的表达特点. 结果 SP表达量在Con、NDFU和DFU组分别为79.64、65.12和45.30 （P＜0.01）.PCNA阳性细胞率在Con、NDFU和DFU组分别为（35.120±7.314）％,（33.880±4.055）％和（28.320±9.332）％,NDFU组与Con、DFU组比较差异有统计学意义（P＜0.01）,但NDFU组和Con组比较差异无统计学意义（P＞0.05）. 结论 DFU患者边缘皮肤中SP表达量减少,可能是导致糖尿病患者创面炎症反应异常及创面修复细胞增殖功能受损,从而引起创面修复受损的原因之一.     

糖尿病足溃疡感染多重耐药铜绿假单胞菌的危险因素及预后分析

目的 探讨糖尿病足溃疡（DFU）感染多重耐药铜绿假单胞菌（MDRPA）的危险因素及其对预后的影响. 方法 将117例DFU感染铜绿假单胞菌（PA）患者根据是否感染MDRPA分为非MDR-PA（N-MDRPA）组和MDRPA组,分析DFU感染MDRPA的危险因素及其对预后的影响. 结果 入院前抗生素应用史、入院前因同一溃疡住院史和骨髓炎是DFU患者感染MDRPA的独立危险因素.MDRPA组较N-MDRPA组截肢/趾率高（32.6％ vs 16.2％,P＜0.05）,治愈率低（20.9％vs41.9％,P＜0.05）. 结论 入院前抗生素应用史、入院前因同一溃疡住院史和骨髓炎是DFU患者感染MDRPA的独立危险因素.MDRPA可导致创面预后差,增加截肢/趾风险.     

MEBT/MEBO对糖尿病足溃疡创面愈合中Smad3、β-catenin mRNA表达的影响

目的采用RT-PCR检测方法观察皮肤原位再生复原技术(Moist Exposed BurnTreatment/Moist Exposed Burn Ointment,MEBT/MEBO)对大鼠糖尿病足溃疡创面愈合的干预作用,研究其促进溃疡创面愈合的机制。方法将100只雄性SD大鼠随机分为空白对照组(20只)和糖尿病造模组(80只),糖尿病造模组大鼠尾静脉注射链脲佐菌素(STZ),成功制备糖尿病大鼠模型64只,从中随机选取60只,并随机分为湿润烧伤膏(MEBO)组(20只)、贝复济组(20只)和模型组(20只)。造模成功后次日开始用药,各组大鼠创面给予相应的药物治疗,并记录创面愈合时间;用药6 d后,采用RT-PCR法观察记录创面肉芽组织中β-catenin mRNA和Smad3 mRNA的表达量。结果 (1)4组大鼠创面平均愈合时间对比,空白对照组愈合时间最短;MEBO组、贝复济组、模型组3组大鼠创面平均愈合时间对比,MEBO组愈合时间最短。(2)用药后第6天,模型组大鼠创面肉芽组织中β-catenin mRNA的表达显著低于空白对照组、MEBO组、贝复济组(P0.01),而MEBO组与贝复济组相比,差异具有统计学意义(P0.05);模型组大鼠创面肉芽组织中Smad3 mRNA的表达显著高于空白对照组、MEBO组、贝复济组(P0.01),而MEBO组与贝复济组相比,差异具有统计学意义(P0.05)。结论 MEBT/MEBO可抑制Smad3 mRNA、增强β-catenin mRNA在实验性糖尿病足溃疡大鼠创面修复中的表达,缩短创面愈合时间,促进糖尿病足溃疡创面的愈合。     

Diabetic foot off loading and ulcer remission: Exploring surgical off-loading

IntroductionDiabetic peripheral neuropathy leads to foot deformity, soft tissues damage, and gait imbalance, all of which can increase the mechanical stress imposed on the foot and give rise to Charcot neuroarthropathy. The current International Working Group of the Diabetic Foot International Guidelines on offloading focus on managing neuropathic foot ulcers related to pressure: only 2 of their 9 recommendations deal with surgical interventions. We assess the role of surgical techniques in off-loading to heal and possibly prevent diabetic foot ulceration.MethodsWe systematically analysed published data from January 2000 to November 2020 to assess methods of surgical offloading and associated outcomes for the surgical reconstruction. We tried to identify healing, remission-rates, return to ambulation, complications and limitations.ResultsFive discrete categories of surgical offloading are used in recalcitrant ulcers: 1. Lesser toe tenotomies; 2. Metatarsal head resection ± Achilles tendon release; 3. Hallux procedures; 4. Bony off-loading procedures in the form of exostectomy; and 5. Complex surgical foot reconstruction. Adjuvant modalities including surgically placed antibiotic delivery systems show promise, but further studies are required to clarify their role and effect on systemic antibiotic requirements.Conclusions and implicationsSurgery is important to mechanically stabilise and harmonise the foot for long term off-loading and foot-protection. Surgery should not be reserved for recalcitrant cases only, but extended to ulcer prevention and remission. Further comparative studies will benefit surgical decision making to avoid recurrence and define time point when surgical off-loading could protect against irretrievable tissue loss/re-ulceration.     

Clinical outcome and determinants of amputation in a large cohort of Iranian patients with diabetic foot ulcers

ObjectiveDetermining the predictive factors of diabetes foot ulcer (DFU) development and lower extremity amputations (LEA) in patients with diabetes mellitus (DM) is of great importance to compose risk stratification models. The aim of this study is to investigate the outcome and predictors of LEA in patients with DFU in large sample of Iranian patients.MethodsThis prospective cohort study was conducted during a 2-year period from 2014 to 2016, in Shiraz, southern Iran. All the patients with type 1 and 2 DM and DFU were included in the cohort and were followed for 2 years at least. They were visited in the clinic on a monthly basis and development of new DFU and LEA were recorded. The two-year free-DFU survival and predictors of the DFU development and LEA were recorded. Multivariate regression models were used to determine the factors.ResultsA total number of 432 patients with mean age of 56.8 ± 13.3 years were included. The two-year DFU-free survival rate was 0.826. The two-year DFU-free survival was associated with male gender (p = 0.005), foot deformity (p = 0.002), history of prior DFU (p < 0.001), cigarette smoking (p = 0.032), nephropathy (p = 0.005), retinopathy (p = 0.007), ischemic heart disease (p = 0.043), and neuropathy (p < 0.001).ConclusionDevelopment of new DFU is associated with higher age, longer duration of disease, and type I diabetes. LEA was associated with increased white blood cell (WBC), Creatinine and ulcer history for major amputation and ulcer history, fasting blood sugar (FBS), infection, revascularization history, and foot deformity, for minor amputation.     

Bioengineered skin in diabetic foot ulcers

Objective: Bioengineered skin (BS) has been shown to play an important role in the treatment of diabetic foot ulcers (DFUs). Whether BS in the therapy of DFU can improve the outcomes still remains uncertain. We performed a quantitative meta‐analysis of available randomized controlled trials to determine the effectiveness and safety of BS in the treatment of patients with DFUs. Design and Methods: Comprehensive search strategies of various electronic databases were used for this study to evaluate the effectiveness and safety between BS and conventional treatment (CT) in patients with DFU, and only randomized controlled trials were adopted in our review. Search terms included ‘bioengineered skin’, ‘tissue‐engineering skin’, ‘human‐tissue graft', ‘human‐skin device’, ‘living‐skin equivalent' and ‘diabetic foot', ‘diabetic ulcer’, ‘diabetic wound’. Analysis outcomes included complete wound closure, complications, ulcer recurrence and adverse severe events (ASEs). Results: Seven randomized controlled trials on BS vs. CT were included, and 880 participants met inclusion criteria. Pooled analysis showed a significant effectiveness and safety advantages for BS treatment compared to CT for patients with DFUs. In analysis of complications, only statistically significant difference of infection was noted. And no included trials reported ASEs related to these treatments. Conclusions: Based on the meta‐analysis, patients with DFUs may benefit from the BS because of its high effectiveness and safety and reduced risk for infections in comparison to CT.     

Cyclo-oxygenase-1 inhibition increases acid secretion by modulating H+,K+-ATPase expression and activation in rabbit parietal cells

1. In the present study, we evaluated the role of cyclo-oxygenase (COX)-1 and COX-2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [(14)C]-aminopyrine uptake, prostaglandin (PG) E(2) synthesis and COX-1, COX-2 and proton pump expression at baseline and after treatment with various concentrations of specific COX-1 (SC-560), COX-2 (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methyl-sulphonyl)phenyl-2 (5H)-furanone; DFU) and non-specific COX (indomethacin) inhibitors. 2. In parietal cells, SC-560 and indomethacin, over the concentration range 10(-8) to 10(-4) mol/L, dose-dependently increased basal and 10(-4) mol/L histamine-stimulated aminopyrine uptake and inhibited PGE(2) synthesis, whereas DFU (10(-8) to 10(-5) mol/L) had no effect. However, at 10(-4) mol/L, DFU augmented histamine-stimulated aminopyrine uptake by 135% and inhibited PGE(2) synthesis by 39%, indicating an inhibition of COX-1 at this higher concentration. 3. The SC-560-, DFU- and indomethacin-induced augmentation of histamine-stimulated aminopyrine uptake was reduced to basal levels after 10(-5) mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10(-4) mol/L ranitidine only partially inhibited such augmentation. 4. Only COX-1 was detected in parietal cells. However, both COX-1 and COX-2 were expressed in gastric glands, with relative protein density of COX-1 being sixfold higher than that of COX-2. Protein levels of COX-1 in parietal cells and those of COX-1 and COX-2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine. 5. Parietal cell proton pump expression was significantly enhanced by 10(-5) mol/L SC-560 and 10(-4) mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10(-5) mol/L DFU had no effect. 6. In conclusion, the data indicate that inhibition of COX-1- but not COX-2-derived PGE(2) synthesis is involved in augmentation of non-steroidal anti-inflammatory drug-induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump.     

自体血小板凝胶在糖尿病足溃疡治疗中的应用研究

目的 观察自体富血小板凝胶治疗糖尿病足溃疡（DFU）的疗效. 方法 72例DFU患者按照数字随机法分为两组.治疗组采用自体富血小板凝胶外敷;对照组采用常规疗法.比较两组DFU治愈率、好转率及愈合时间. 结果 两组间年龄、糖尿病病程、FPG、FIns、HbA1c、稳态模型评估胰岛素抵抗指数（HOMA-IR）、BMI、TG、TC、LDL-C、HDL-C、溃疡面积及溃疡体积比较差异均无统计学意义（P＞0.05）.两组Wagner Ⅰ级DFU治疗的疗效比较差异均无统计学意义（P＞0.05）.在WagnerⅡ、Ⅲ级DFU病例中,治疗组治愈率（66.7％、70.0％）、总有效率（94.4％、90.0％）均高于对照组（治愈率：26.3％、57.9％;总有效率：10.0％、30.0％）（P＜0.05）;治疗组Wagner Ⅰ～Ⅲ级DFU愈合时间均短于对照组[WagnerⅠ级：（14.75±1.82） vs （22.00±1.63）d;WagnerⅡ级：（27.12±2.15） vs （34.93±1.44）d;WagnerⅢ级：（41.89±3.22） vs （53.83±1.17）d] （P＜0.05）. 结论 自体富血小板凝胶可能具有促进DFU愈合的作用.     

特异性环氧化酶2抑制剂-双脱氧氟尿苷(DFU)在动脉粥样硬化中的作用

目的本研究观察高脂餐诱导的兔AS模型中,COX-2在AS发生和早期病变中的表达,以及在此过程中增生内膜降解基质的能力、胶原含量、内弹力板的变化;以及DFU[5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)-phenyl-2-(5H)-furanone]-特异性COX-2抑制剂的作用。方法42只6周龄雄性新西兰大白兔(NZW),饲以高脂餐(2%胆固醇 3%猪油),参考血脂反应程度,随机分为四组,在高脂餐的同时,分别管饲安慰剂与不同剂量的DFU。4周后取主动脉(主动脉根部-髂动脉分叉)。主动脉弓前1/3切片,行HE染色;后2/3匀浆,测明胶酶活性及免疫印迹检测MMP-2。其余主动脉标本纵向剖开,以4%中性甲醛固定,苏丹Ⅳ染色,内膜拍照,Matlab软件分析粥样硬化斑块面积占内膜总面积比例。结果主动脉内膜COX-2随AS的进展表达逐渐增高。DFU对各组体重、血浆总胆固醇与甘油三酯无显著性影响。不同剂量DFU组AS面积比例分别为:对照组,0.330±0.052(n=7);实验1组,0.273±0.042(n=6);实验2组,0.314±0.089(n=8);实验3组,0.288±0.036(n=9)。与对照相比,DFU对实验1、23、组主动脉AS面积没有明显影响(P>0.50)。DFU对病变血管内MMP-2的表达和活性亦没有影响。结论COX-2与AS发生和进展相关,但未发现特异性COX-2抑制剂DFU对AS进展的抑制作用。     

MEBT/MEBO治疗糖尿病足溃疡的临床疗效观察

目的观察应用皮肤再生医疗技术(Moist Exposed Bunn Therapy/Moist Exposed Burn Ointment,MEBT/MEBO)治疗WagnerⅡ级糖尿病足溃疡的疗效,并探讨其修复创面的机制。方法选择2013年1月至2015年1月右江民族医学院附属医院和广西中医药大学第一附属医院收治的WagnerⅡ级糖尿病足溃疡患者81例,随机分为湿润烧伤膏组(43例)和贝复济组(38例),分别外用湿润烧伤膏和贝复济凝胶治疗,每日1次分别于用药后第1、10、20天观察创而修复情况。结果用药后第10、20天,湿润烧伤膏组患者创面较贝复济组患者创面明显缩小,差异具有统计学意义(P<0.05),治疗20 d后,湿润烧伤膏组治愈27例、显效15例、有效1例;贝复济组治愈12例,显效20例,有效6例,差异具有统计学意义(P<0.05)。结论湿润烧伤膏可有效促进WagnerⅡ级糖尿病足溃疡创面愈合,临床疗效肯定。