Background:Chronic nonhealing wounds are major complications in diabetic patients, with impaired angiogenesis playing a critical role in the delayed healing process. Current treatments for diabetic wounds are inadequate. The dysregulation of endothelial cell genes, particularly thrombospondin-1 (TSP-1), impairs neovascularization and delays wound repair. In recent years, hydrogel-based wound dressings have gained widespread application in biomedicine. The study introduced a new therapeutic approach, embedding miR-221-3p-loaded small extracellular vesicles (miR-221OE-sEVs) within gelatin methacryloyl (GelMA) hydrogels to reduce TSP-1 levels and improve healing in diabetic wounds. Methods:First, we observed upregulated TSP-1 expression in human umbilical vein endothelial cells (HUVECs) when cultured in a high-glucose (HG) environment. We employed small interfering RNA (siRNA) and miR-221-3p to suppress TSP-1 expression and then evaluate the functional effects on HUVECs. Subsequently, miR-221-3p was encapsulated in sEVs via lentiviral transfection. The effects of miR-221OE-sEVs on HUVECs under HG conditions were evaluated. Finally, miR-221OE-sEVs were incorporated into a GelMA hydrogel (G-miR-221OE-sEVs) and applied to a diabetic murine wound model to evaluate their effects on wound closure and angiogenesis. Results:Under HG conditions, the use of siTSP-1 to silence TSP-1 enhanced the proliferation, migration, and tube formation capabilities of HUVECs. Similarly, miR-221-3p treatment exerted proregenerative effects via the targeting of TSP-1. We successfully generated miR-221OE-sEVs that exhibited a 28-fold increase in miR-221-3p expression, which significantly enhanced HUVEC functionality under HG conditions. Encapsulation within the GelMA hydrogel enabled G-miR-221OE-sEVs to significantly accelerate diabetic wound healing via increased angiogenesis. Conclusions:This study demonstrated the successful fabrication of a novel bioactive wound dressing (G-miR-221OE-sEVs), which promotes diabetic wound healing by promoting angiogenesis through the regulation of TSP-1. This approach offers a potential therapeutic option for enhancing the management of diabetic wounds.

During skin aging, the degeneration of epidermal stem cells (EpiSCs) leads to diminished wound healing capabilities and epidermal disintegration. This study tackles this issue through a comprehensive analysis combining transcriptomics and untargeted metabolomics, revealing age-dependent alterations in the Gpx gene family and arachidonic acid (AA) metabolic networks, resulting in enhanced ferroptosis. Selenomethionine (Se-Met) could enhance GPX4 expression, thereby assisting EpiSCs in countering AA-induced mitochondrial damage and ferroptosis. Additionally, Se-Met demonstrates antioxidative characteristics and extensive ultraviolet absorption. For the sustained and controllable release of Se-Met, it was covalently grafted to UV-responsive GelMA hydrogels via AC-PEG-NHS tethers. The Se-Met@GelMA hydrogel effectively accelerated wound healing in a chronological aging mice model, by inhibiting lipid peroxidation and ferroptosis with augmented GPX4 expression. Moreover, in a photoaging model, this hydrogel significantly mitigated inflammatory responses, extracellular matrix remodeling, and ferroptosis in UV-exposed mice. These characteristics render Se-Met@GelMA hydrogel valuable in practical clinical applications.

Background: Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. Method: This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. Results: The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI, 0.917-0.960) and 0.966 (95% CI, 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. Conclusion: This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.

This study attempted to investigate the role and mechanism of endoplasmic reticulum (ER) stress in the islet dysfunction in mice after severe burns. C57BL/6 mice were randomly divided into the sham group, burn group, and burn+4-phenylbutyric acid (4-PBA) group. Mice were burned with full thickness of 30% total surface area (TBSA), and 4-PBA solution was intraperitoneally injected into mice in burn+4-PBA group. Glucose-stimulated insulin secretion (GSIS), Fasting blood glucose (FBG) and glucose tolerance were detected 24 hours post severe burns. The ER stress-related pathway markers immunoglobulin binding protein (BIP), X-box binding protein 1 (XBP1), phosphorylation-PKR-like ER kinase (p-PERK), phosphorylation-eukaryotic translation initiation factor 2α (p-eIF2α), CHOP, activating transcription factor 6 (ATF6), apoptosis-related protein Cleaved-Caspase 3, and islet cell apoptosis were measured. Mice were characterized with elevated FBG, decreased glucose tolerance and GSIS levels post severe burns. The expression of BIP, XBP1, p-PERK, p-eIF2α, CHOP, ATF6, Cleaved-Caspase 3, and islet cell apoptosis were increased significantly after severe burns. 4-PBA treatment contributed to decreased FBG, improved glucose tolerance, increased GSIS, inhibited islet ER stress, and reduced pancreatic islet cell apoptosis in mice post severe burns. ER stress occurs in islets of severely burned mice, which leads to increased apoptosis of islet cells, thus resulting in islet dysfunction.

Aim: The aim of this study was to explore the epidermal barrier structure and function of re-harvested skin from non-scalp donor sites. Methods: Six patients with large-area deep burns who met the inclusion and exclusion criteria were subjected to split-thickness skin excision three times on the same healthy non-scalp donor sites, with an interval of 14 days. The donor skin thus harvested was labeled as primary skin (S1), secondary skin (S2), and tertiary skin (S3). The transepidermal water loss (TEWL) and stratum corneum water content (SCH) of donor skin were detected before each surgery, and the donor skin was harvested during the surgery. The donor skin was stained with hematoxylin and eosin (HE) and involucrin, loricrin, filaggrin, small molecule proline-rich protein 3 (SPRR3), ZO-3, JAM-A, and JAM-C, or observed by transmission electron microscopy. Results: The epidermal barrier function of the re-harvested skin from the non-scalp donor sites became impaired. The histopathological structure of the re-harvested skin from non-scalp donor sites became abnormal. The barrier of the epidermal stratum corneum of the re-harvested skin from non-scalp donor sites was damaged. The epidermal tight junction barrier in the re-harvested skin from non-scalp donor sites was damaged. Conclusions: As the number of harvesting increases, the epidermal barrier function of the skin decreased, and the damage to the barrier structure increased. Hence, it is vitally important to restore the epidermal barrier function for re-harvesting in non-scalp donor sites.

This study was designed to analyse the characteristics and aetiology of low-temperature burns and explore the prevention and treatment strategies. In total, 206 patients hospitalised with low-temperature burns in a major burn center in Beijing from 2017 to 2021 were included. There were 35-49 cases per year, with an average of 41 ± 4.5 cases. The prevalence of low-temperature burns was higher in female than in male and are mainly resulted from two kinds of incidents: unintended burns from heat treatment (50.97%, 105/206) and improper use of heating devices to keep warm (43.69%, 90/206). Most cases occurred in autumn (33.01%, 68/206) and the least in spring (17.96%, 37/206); cases in summer (24.27%, 50/206) and winter (24.76%, 51/206) accounted for nearly a quadrant respectively. Low-temperature burns in summer were mainly unintended burns from heat treatment (80%, 40/50), whereas in autumn were mainly resulted from improper use of heating devices to keep warm (55.88%, 38/68), the difference was statistically significant (χ2  = 42.801, P < .001). Of all the cases, the burn size ranged from 0.2% to 5% TBSA, mostly less than 1% (85.92%, 177/206); third-degree burns accounted for 98.54% (203/206). Patients admitted after 3 weeks post-injury accounted for 42.23% (87/206). All patients were cured, and most of them were by surgeries (70.87%, 146/206). The results of the study show that low-temperature burn injury features a predictable morbidity among different seasons, a higher prevalence in adult women and a frequent occurrence at home. The wounds of low-temperature burns are often small in size but deep in depth, and can be easily misdiagnosed as superficial burns. However, most low-temperature burn wounds require surgical treatment. The study also suggests that based on the characteristics and aetiology of low-temperature burns, targeted prevention and treatment measures should be mapped out.

Background: Severe burns are often complicated with hyperglycemia caused by mitochondrial oxidative stressrelated pancreatic islet dysfunction. Silent information regulator of transcription 3 (Sirt3) can regulate mitochondrial oxidative stress. However, the role and mechanism of Sirt3 on islet function after severe burns remain unclear. Therefore, this study aimed to investigate whether Sirt3 played a role in both mitochondrial oxidative stress in islets and mediating islet function post severe burns.Methods: A mouse model of 30% total body surface area full-thickness burn and an in vitro MIN6 cell hypoxia model were established. Sirt3 KO mice were used to demonstrate further the role of Sirt3 in maintaining redox homeostasis and regulating islet function. Fasting blood glucose and glucose-stimulated insulin secretion (GSIS) were detected to assess the islet function. The levels of mitochondrial ROS and deacetylation, and the activities of Mn-SOD and IDH2 were measured to evaluate oxidative stress. The mitochondrial membrane potential (MMP) was detected and the apoptosis rate measured. Results: In vitro MIN6 cells, the hypoxia treatment significantly reduced Sirt3 expression, resulting in increased deacetylation of Mn-SOD and IDH2, which further led to a higher level of mitochondrial ROS. In addition, hypoxia reduced MMP and increased apoptosis rate, which impaired GSIS eventually. Knockdown of Sirt3 caused similar alterations. The hypoxia-induced high level of mitochondrial ROS and apoptosis and impaired GSIS could be reversed by overexpression of Sirt3. Similarly, after severe burns, the expression of Sirt3 in islets decreased significantly with a high level of deacetylation of Mn-SOD, IDH2, mitochondrial ROS and apoptosis, and islet dysfunction. Oxidative stress and apoptosis also occurred in islets of Sirt3 KO mice, accompanied by islet dysfunction.Conclusions: Sirt3 and downstream signalling are critical in modulating the islet function post severe burns by regulating mitochondrial oxidative stress and apoptosis.

目的:比较国产和进口医用直线加速器及治疗计划系统在肺癌调强放疗中的临床剂量学差异.方法:选取3家医院进行研究,分别使用进口医用直线加速器与进口治疗计划系统(作为A组)、国产医用直线加速器与进口治疗计划系统(作为B组)、国产医用直线加速器与国产治疗计划系统(作为C组).从A组单位随机抽取20例接受调强放疗的肺癌患者,将患者的靶区和危及器官图像分别传输至B组和C组的治疗计划系统进行放疗计划设计和临床剂量学验证(在放疗计划设计中要保证靶区的处方剂量和危及器官的剂量限值与A组一致).比较3组计划的靶区受照射剂量、适形度指数(conformity index,CI)、均匀度指数(homogeneity index,HI),危及器官(肺、心脏、脊髓)的受照射剂量,剂量验证的Gamma通过率.采用SPSS 19.0软件进行统计学分析.结果:在计划靶区(planning target volume,PTV)方面,C组的V105、V110及Dmean均显著高于A组和B组(P<0.05),3组的CI无明显差异(P>0.05);B组的HI优于A组和C组(P<0.05).在肿瘤靶区(gross tumor volume,GTV)方面,3组的V105、V110、Dmean、CI和HI均无明显差异(P>0.05).C组的危及器官受照射剂量全肺V5和Dmean、心脏V30和Dmean及脊髓Dmax均优于A组和B组(P<0.05).3组的3 mm/3％与4 mm/4％标准下的剂量验证Gamma通过率均在95％以上,差异无统计学意义(P>0.05).B组的2 mm/2％标准下的剂量验证通过率高于C组(P<0.05),但与A组没有明显差异(P>0.05).结论:国产和进口医用直线加速器及治疗计划系统在靶区及危及器官的剂量分布上均能满足临床要求,可以用于肺癌的调强放疗.

背景 衰弱指老年人生理储备下降导致的机体易损性增加、抗应激能力减退的非特异性状态,老年衰弱患者住院期间发生跌倒、感染、住院时间延长、死亡等不良事件的风险增加.目的 评估高龄老年男性住院患者的衰弱状态,探索其衰弱的相关因素.方法 收集2019年1月- 2020年1月在解放军总医院第二医学中心住院的年龄≥80岁男性患者的临床资料,采用Fried衰弱表型量表评估后分为衰弱组和非衰弱组.进行单因素和多因素logistic回归分析衰弱的关联因素.结果 本研究共纳入133例患者,平均年龄(90.22 ± 5.37)岁,老年慢性疾病中位患病数为2(2,3)种.经Fried量表评分纳入衰弱组77例 (57.89%),非衰弱组 56例 (42.11%).单因素分析结果显示,衰弱组年龄、总铁结合力 (total iron binding capacity, TIBC)、中重度贫血、慢性肺病、癌症的构成比均显著高于非衰弱组(P ＜ 0.05),其中中重度贫血患者的衰弱患病率高达81.5%.多因素logistic回归分析显示,增龄(OR=1.151, 95% CI: 1.052～1.260)、高TIBC水平(OR=1.038, 95% CI: 1.003～1.074)、中重度贫血(OR=5.975,95% CI:1.112～32.093)是衰弱的关联因素(P＜0.05),且中重度贫血与TIBC衰弱风险具有乘性交互作用(P ＜ 0.05).根据多因素logistic回归模型,拟合中重度贫血、TIBC水平和年龄的受试者工作特征曲线,曲线下面积为0.820,且拟合度良好(χ2=10.244,P=0.248),高于中重度贫血(AUC=0.597)和TIBC(AUC=0.619)单独预测衰弱的曲线下面积.结论 高龄、中重度贫血和TIBC增高与男性老年共病发生衰弱密切相关,及时有效干预可能有助于衰弱的防控.

BACKGROUND:Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing.METHODS:Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed.RESULTS:The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group.CONCLUSION:In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production.

缺血性心脏病(ischemic heart disease,IHD)是全球范围内危害人类健康的重大公共卫生问题,研究显示我国现有冠心病患者1100万,每年有超过100万人死于IHD导致的急性心肌梗死(acute myocardial infarction,AMI)及其并发症,给家庭和社会带来巨大的经济和医疗负担[1-3].因此,降低IHD患者的致死、致残率对个人和社会都具有十分重要的意义.IHD发生的主要病理生理机制是先天性冠状动脉发育异常或后天性动脉粥样硬化引起的血管狭窄或闭塞,造成心肌供血不足,难以满足机体正常生理需求,最终产生胸闷、胸痛等症状,导致AMI的发生.

目的 应用凝血酶智能响应型纳米探针,实现颈动脉血栓的体内可视化预测,为血栓形成的早期诊断提供新策略.方法 将超顺磁性氧化铁与凝血酶响应肽及Cy5.5-N-羟基琥珀酰亚胺酯(Cy5.5 NHS)共价偶联构建探针.检测不同浓度探针(0μg/ml、10 μg/ml、20 μμg/ml、50 μg/ml、100 μg/ml、200 μμg/ml)对人脐静脉内皮细胞的毒性.近红外荧光成像分析加入不同浓度凝血酶的探针荧光强度(实验组:凝血酶浓度分别为0.5 U/ml、1 U/ml、10 U/ml、50 U/ml;空白对照组为0 U/ml;阴性对照组为50 U/ml,并加入100 μg比伐芦定).制备小鼠颈动脉血栓模型,并对血栓组和对照组小鼠颈动脉组织切片进行免疫荧光染色,以探究探针的凝血酶靶向性.结果 不同探针浓度的细胞存活率比较无统计学差异(P＞0.05).不同浓度实验组探针荧光强度分别为空白对照组的17.64、34.24、55.01和64.65倍(P＜0.01),阴性对照组与空白对照组探针荧光强度比较无显著差异(P＞0.05).血栓组小鼠病变局部凝血酶水平较对照组显著升高.结论 本研究成功构建凝血酶智能响应型纳米探针,实现颈动脉血栓的早期精准识别,为血栓形成的可视化预测提供了新策略.

Ischemic heart disease refers to myocardial degeneration, necrosis, and fibrosis caused by coronary artery disease. It can lead to severe left ventricular dysfunction (LVEF ≤ 35–40%) and is a major cause of heart failure (HF). In each contraction, myocardium is subjected to a variety of mechanical forces, such as stretch, afterload, and shear stress, and these mechanical stresses are clinically associated with myocardial remodeling and, eventually, cardiac outcomes. Mitochondria produce 90% of ATP in the heart and participate in metabolic pathways that regulate the balance of glucose and fatty acid oxidative phosphorylation. However, altered energetics and metabolic reprogramming are proved to aggravate HF development and progression by disturbing substrate utilization. This review briefly summarizes the current insights into the adaptations of cardiomyocytes to mechanical stimuli and underlying mechanisms in ischemic heart disease, with focusing on mitochondrial metabolism. We also discuss how mechanical circulatory support (MCS) alters myocardial energy metabolism and affects the detrimental metabolic adaptations of the dysfunctional myocardium.

The incidence of atrial fibrillation (AF) increases with age, and telomere length gradually shortens with age. However, whether telomere length is related to AF is still inconclusive, and the exact mechanism by which aging causes the increased incidence of AF is still unclear. We hypothesize that telomere length is correlated with aging-related AF and that mitochondrial dysfunction plays a role in this. This research recruited 96 elderly male patients with AF who were admitted to the Second Medical Center of Chinese PLA General Hospital from April to October 2018. After matching by age and gender, 96 non-AF elderly male patients who were admitted to the hospital for physical examination during the same period were selected as controls. Anthropometric, clinical, and laboratory analyses were performed on all subjects. The mitochondrial membrane potential (MMP) of peripheral blood leukocytes was detected as the indicator of mitochondrial function. Compared with the control group, the leukocyte telomere length (LTL) was significantly shorter ( P < 0.001 ), and the level of PGC-1α in serum was significantly lower in AF patients. Additionally, in subjects without any other diseases, the AF patients had lower MMP when compared with the control. Multivariate logistic regression confirmed that LTL (OR 0.365; 95% CI 0.235-0.568; P < 0.001 ) and serum PGC-1α (OR 0.993; 95% CI 0.988-0.997; P = 0.002 ) were inversely associated with the presence of AF. In addition, ROC analysis indicated the potential diagnostic value of LTL and serum PGC-1α with AUC values of 0.734 and 0.633, respectively. This research concludes that LTL and serum PGC-1α are inversely correlated with the occurrence of aging-related AF and that mitochondrial dysfunction plays a role in this.

近年来,随着对医学教育方式的不断创新和探索,医学教育模式改革已成为被广泛关注的热点,教师如何使用翻转课堂这种教学方法 让学生积极主动地学习是现阶段教育改革急需解决的问题.文章通过分析翻转课堂教学的发展历程及其最新应用,对实施翻转课堂所带来的效果进行了总结与评价.

人体五脏六腑出现问题将会导致疾病的发生,五脏六腑是人体重要的脏器,各脏器发挥着不同的作用.若五脏六腑"不通",必将导致多种疾病的发生.因此,"以通为用"观念在看待正常五脏六腑时极其重要,在治疗五脏六腑相关疾病时,也具有重大意义.本文就从"以通为用"来论述五脏六腑与疾病的关系.

Objective: Telomeres gradually shorten and the incidence of atrial fibrillation (AF) gradually increases with age. However, the association of telomere length with AF is still controversial. This study aims to determine the correlation between the leukocyte telomere length (LTL) and the presence of AF. Methods: This study recruited 96 AF male patients and 97 healthy male controls (aged ≥60 years) Anthropometric, clinical and laboratory analysis were performed on all subjects. Blood LTL was detected by quantitative real-time PCR assay. PGC-1α concentration was evaluated by ELISA method. The association between LTL and AF was analyzed by simple and multivariate logistic regression. Results: LTL in AF patients was significantly shorter than controls (P < 0.001). Logistic regression analysis confirmed that LTL was inversely associated with the presence of AF (OR 0.428, 95% confidence interval [CI]: 0.268-0.684; P < 0.001). Furthermore, we conducted a subgroup analysis of different ages and different types of AF and found that LTL was negatively correlated with age (r = -0.148, P = 0.040), and there was no statistical difference among different types of AF. We found that the telomere-associated molecule serum PGC-1α concentration was also negatively related to AF (OR 0.991, 95% CI: 0.985-0.997; P = 0.004) . Conclusion: LTL and serum PGC-1α concentration are inversely correlated with the presence of AF in elderly male.

Context Having been used for thousands of years to treat gastrointestinal diseases, the natural isoquinoline alkaloid, berberine, has exhibited a wide spectrum of biochemical and pharmacological effects in studies of recent years. Objective The review intended to examine the many novel bioactivities of berberine, including antidiabetic, anticancer, neuroprotective, anti-inflammatory, and anti-atherosclerotic actions. Design The research team searched the MEDLINE database using PubMed, using different keyword combinations, including berberine AND diabetes, berberine AND cancer, berberine AND (neuron OR brain), berberine AND inflammation, and "berberine AND atherosclerosis to find studies evaluating the various effects exerted berberine. Conclusion Berberine is a promising multipotent agent to combat diabetes, cancer, Alzheimer's disease, and other diseases.