How good is the evidence that cellular senescence causes skin ageing?

Skin is the largest organ of the body with important protective functions, which become compromised with time due to both intrinsic and extrinsic ageing processes. Cellular senescence is the primary ageing process at cell level, associated with loss of proliferative capacity, mitochondrial dysfunction and significantly altered patterns of expression and secretion of bioactive molecules. Intervention experiments have proven cell senescence as a relevant cause of ageing in many organs. In case of skin, accumulation of senescence in all major compartments with ageing is well documented and might be responsible for most, if not all, the molecular changes observed during ageing. Incorporation of senescent cells into in-vitro skin models (specifically 3D full thickness models) recapitulates changes typically associated with skin ageing. However, crucial evidence is still missing. A beneficial effect of senescent cell ablation on skin ageing has so far only been shown following rather unspecific interventions or in transgenic mouse models. We conclude that evidence for cellular senescence as a relevant cause of intrinsic skin ageing is highly suggestive but not yet completely conclusive.     

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, with several underlying pathophysiological mechanisms, some of which are still uncertain. The cornea is an avascular tissue and sensitive to hyperglycemia, resulting in several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity, and tear film changes. The manifestation of DPN in the cornea is referred to as diabetic neurotrophic keratopathy (DNK). Recent studies have revealed that disturbed epithelial-neural-immune cell interactions are a major cause of DNK. The epithelium is supplied by a dense network of sensory nerve endings and dendritic cell processes, and it secretes growth/neurotrophic factors and cytokines to nourish these neighboring cells. In turn, sensory nerve endings release neuropeptides to suppress inflammation and promote epithelial wound healing, while resident immune cells provide neurotrophic and growth factors to support neuronal and epithelial cells, respectively. Diabetes greatly perturbs these interdependencies, resulting in suppressed epithelial proliferation, sensory neuropathy, and a decreased density of dendritic cells. Clinically, this results in a markedly delayed wound healing and impaired sensory nerve regeneration in response to insult and injury. Current treatments for DPN and DNK largely focus on managing the severe complications of the disease. Cell-based therapies hold promise for providing more effective treatment for diabetic keratopathy and corneal ulcers.     

新型胸骨环抱器结合钢丝固定胸骨的临床效果

目的探讨新型胸骨环抱器结合钢丝固定胸骨在成人心脏正中切口直视手术中的应用效果。 方法回顾性分析2016年1月至2017年12月期间在临沂市人民医院心脏血管外科接受手术治疗的328例心脏大血管疾病患者临床资料，按胸骨固定方法不同分为对照组159例和研究组169例。其中对照组采用传统的钢丝将锯开的胸骨左右两侧缝合，后收紧钢丝、合拢胸骨并拧紧钢丝，予以固定胸骨；研究组采用钢丝对合锯开胸骨的基础上放置新型环抱器固定胸骨。分析2组患者关胸时间(关胸开始到皮肤切口缝合结束的时间)、二次开胸止血(胸骨相关)率、术后24 h引流量、术后切口、胸骨感染或胸骨裂开率、术后胸痛不适发生率以及术后住院时间。患者出院后通过门诊、电话询问进行随访。数据比较采用t检验和χ²检验。 结果关胸术后，对照组1例患者因急性A型主动脉夹层术后急性肾功能衰竭死亡，其余所有患者均痊愈出院。研究组患者关胸时间(32.3±7.3) min，明显少于对照组(51.5±8.4) min，差异有统计学意义(t＝－22.113，P<0.05)。胸骨相关的二次开胸止血，研究组发生1例，而对照组发生6例，2组比较差异有统计学意义(χ²＝3.969，P＝0.046)。研究组术后24 h引流量(372.8±213.1) mL，少于对照组(538.9±202.6) mL，2组比较差异有统计学意义(t＝－7.224，P<0.05)。研究组术后未见切口和胸骨感染和(或)裂开，而对照组感染和(或)裂开共7例，其中胸骨裂开4例，早期予以新型环抱器重新固定胸骨，治愈出院；切口感染2例，予以换药后重新缝合切口后治愈；胸骨感染1例，予以胸骨清创加胸大肌肌瓣转移手术后康复出院，2组比较差异有统计学意义(χ²＝7.599，P<0.05)。研究组术后出现胸痛不适2例，而对照组7例，2组比较差异有统计学意义(χ²＝4.101，P＝0.043)。研究组患者术后住院时间(8.6±4.1) d，少于对照组(10.5±3.4) d，2组比较差异有统计学意义(t＝－4.467，P<0.05)。患者出院后随访(11.3±4.9)个月，所有患者均未见胸骨感染及裂开。 结论新型胸骨环抱器结合钢丝固定胸骨手术切口，与传统手术相比操作简单、固定牢固，在缩短关胸手术时间、减少术后切口并发症、缩短住院时间等方面优势明显，可以广泛使用于成人心脏外科正中手术切口。     

Nano-silver modified porcine small intestinal submucosa for the treatment of infected partial-thickness burn wounds

Background and aimSilver has been widely used as a topical antimicrobial agent in burn wound care. In a previous study, we demonstrated the introduction of nano-silver particles to porcine small intestinal submucosa (NS-PSIS) led to significant enhancement in antibacterial property in repairing contaminated abdominal defect. In this study, we explored the efficacy of NS-PSIS in the treatment of Pseudomonas aeruginosa-infected partial-thickness burn wounds.Methods48 male Sprague-Dawley rats were divided into four groups of equal number. Standardized and reproducible Pseudomonas aeruginosa-infected partial-thickness thermal burns wound model were created using these rats. NS-PSIS, PSIS (porcine small intestinal submucosa) or lipido-colloid dressingss (Urgotul?) were tested for 14 days to assess their ability to heal the rats’ burn wounds. Control group was without any treatment after the establishment of infected burn-wound. The wound contraction rate, animal body weight change, histological examination, and the quantification of IL-6 and C-reactive protein (CRP) were measured to evaluate the healing effects.ResultsNS-PSIS significantly promoted wound healing and recovered the normal growth of rats. There were significantly lower expression levels of pro-inflammatory cytokine (IL-6) and CRP in NS-PSIS group as compared with the PSIS or Urgotul group in the treatment of infected partial-thickness burn wounds. Histological exams revealed significant less inflammatory cells infiltrating, more re-epithelization and neovascularization in NS-PSIS group. There were also less inflammatory cells infiltrations in the major organs in NS-PSIS group.ConclusionsNano-silver modified porcine small intestinal submucosa (NS-PSIS) can be used as a biological derivative dressing for the treatment of infected partial-thickness burn wounds.