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The aim is to investigate the prognostic value of the factors related to the initial surgical management of burn wounds in severely burned patients. A total of 189 severely burned adult patients who were admitted to our institute between January 2012 and December 2020 and met the inclusion criteria were recruited. Patients were divided into survival and nonsurvival groups. The patient data included sex, age, total burn surface area (TBSA), burn index, inhalation injury, mechanical ventilation, initial surgical management of the burn wound (including postinjury time before surgery, surgical duration, surgical area, intraoperative fluid replenishment, intraoperative blood loss, and intraoperative urine output), and duration in the burn intensive care unit (BICU). Independent samples t-tests, Mann–Whitney U-tests, and χ 2 tests were performed on these data. Those of which with statistically significant differences were subjected to univariate and multivariate Cox regression analyses to identify independent risk factors affecting the prognosis of severely burned patients. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) and optimal cutoff value were calculated. Patients were divided into two groups, according to the optimal cutoff value of the independent risk factors. The TBSA, surgical area, and survival rates of the two groups during hospitalization were analyzed. The survival group (146 patients) and the nonsurvival group (43 patients) differed significantly in TBSA, burn index, inhalation injury, mechanical ventilation, initial surgical area, intraoperative fluid replenishment, intraoperative blood loss, and duration in the BICU (P < .05). Univariate Cox regression analysis showed that TBSA, burn index, mechanical ventilation, initial surgical area, intraoperative fluid replenishment, and intraoperative blood loss were risk factors for death in severely burned patients (P < .05). Multivariate Cox regression analysis showed that the burn index and intraoperative blood loss were independent risk factors for death in severely burned patients (P < .05). When the intraoperative blood loss during the initial surgical management of burn wounds was used to predict death in 189 severely burned patients, the AUC was 0.637 (95% confidence interval: 0.545–0.730, P = .006), and the optimal cutoff for intraoperative blood loss was 750 ml. Kaplan–Meier survival analysis showed that the prognosis of the group with intraoperative blood loss ≤750 ml was better than that of the group with intraoperative blood loss >750 ml (P = .008). Meanwhile, the TBSA and surgical area in the group with intraoperative blood loss ≤750 ml were significantly lower than that of the group with intraoperative blood loss >750 ml (P < .05). The burn index and intraoperative blood loss during the initial surgical management of burn wounds are independent risk factors affecting the outcome of severely burned patients with good predictive values. During surgery, hemostatic and anesthetic strategies should be adopted to reduce bleeding, and the bleeding volume should be controlled within 750 ml to improve the outcome.

Burns are common injuries associated with high disability and mortality. In recent years, Meek micrografting technique has been gradually applied for the wound treatment of severe burns. However, the efficacy of two-stage Meek micrografting in patients with severe burns keeps unclear. The data of eligible patients with severe burns who were admitted to Southwest Hospital of the Third Military Medical University from January 2013 to December 2019 were retrospectively analyzed. The patients were divided into two groups according to the Meek micrografting method: one-stage skin grafting (group A) and two-stage skin grafting (group B). The baseline data, survival rate of skin graft, length of hospital stay, treatment costs, laboratory data, and cumulative survival were statistically analyzed. One hundred and twenty-seven patients (91 in group A and 36 in group B) were included in the study. There was no significant difference in the baseline data, the length of hospital stay, and treatment costs between the two groups. The survival rate of skin graft was higher in group B. Total protein and albumin level, platelet count in group B were superior to those in group A, while there was no difference in other laboratory data (prealbumin, serum creatinine, urea nitrogen, cystatin C, blood cultures, wound exudate cultures), and cumulative survival between the two groups. Our results demonstrated that staged Meek micrografting could improve the survival rate of skin graft, by reducing the risks of hypoproteinemia, hypoalbuminemia, and low platelet counts after adequate resuscitation.

Chronic wounds have become one of the major issues in medicine today, the treatments for which include dressing changes, negative pressure wound therapy (NPWT), hyperbaric oxygen, light irradiation, surgery, etc. Nevertheless, the application of diode lasers in chronic wounds has rarely been reported. This retrospective cohort study aimed to evaluate the therapeutic effect of diode laser (810nm) irradiation on chronic wounds. 89 patients were enrolled in the study. The control group (41 patients) received traditional dressing change therapy, while the diode laser treatment group (48 patients) were patients received additional treatment with diode laser (810 nm) irradiation for 10 minutes at each dressing change. Wound healing time was compared between two groups, while the pain relief index was creatively introduced to evaluate the effect of relieving wound pain, which was calculated by the difference in pain scores between the first and last dressing changes divided by the number of treatment days. The wound healing time of the diode laser treatment group was 22.71±8.99 days, which was significantly shorter than that of the control group (37.44±23.42 days). The pain relief index of the diode laser treatment group was 0.081±0.055, which was significantly increased compared with that of the control group (0.057±0.033). Our findings suggest that diode laser irradiation has the potential to promote healing in chronic wounds and relieve wound pain. This article is protected by copyright. All rights reserved.

The aim is to examine the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with major burns and sepsis. We collected the data of major burn patients who were admitted to our department. We compared the age, sex, burn area, burn depth, length of hospitalization, and mortality rate between the sepsis group and non-sepsis group and compared NT-proBNP, procalcitonin (PCT), platelet count, Sequential Organ Failure Assessment (SOFA) score, and quick SOFA (qSOFA) score between the survivors and nonsurvivors in the sepsis group. Receiver operating characteristic (ROC) curves were used in sepsis patients to evaluate the prognostic value of NT-proBNP, PCT, SOFA score, qSOFA score, etc. Kaplan–Meier survival curves were used to compare the 90-day survival curves of patients. Logistic regression analysis was used to analyze the risk factors that affect the prognosis of sepsis patients. There were 90 major burn patients with sepsis and 114 major burn patients without sepsis. The mortality rate for the major burn sepsis group was significantly higher than that for the non-sepsis group. The NT-proBNP level in sepsis patients in the nonsurvivor group was 2900 pg/ml, which was significantly higher than that in patients in the survivor group. Survival analysis showed that the mean survival time for the NT-proBNP >2000 pg/ml group was 15.08 days. Multivariate regression analysis indicated that NT-proBNP was an independent risk factor for mortality in burn patients with sepsis. NT-proBNP can be used as a prognostic marker in patients with major burns and sepsis.

Severe burns often cause various systemic complications and multiple organ dysfunction syndrome, which is the main cause of death. The lungs and kidneys are vulnerable organs in patients with multiple organ dysfunction syndrome after burns. Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) have been gradually applied in clinical practice and are beneficial for severe burn patients with refractory respiratory failure or renal dysfunction. However, the literature on ECMO combined with CRRT for the treatment of severe burns is limited. Here, we focus on the current status of ECMO combined with CRRT for the treatment of severe burns and the associated challenges, including the timing of treatment, nutrition support, heparinization and wound management, catheter-related infection and drug dosing in CRRT. With the advancement of medical technology, ECMO combined with CRRT will be further optimized to improve the outcomes of patients with severe burns.

Venous leg ulcers are a manifestation of lower extremity chronic venous disorder. Venous hypertension caused by abnormal venous blood flow is considered to be the primary mechanism of venous ulcers. The etiology of lower extremity venous ulcer is complicated, and it is difficult to be treated. At present, it has achieved a certain effect for venous leg ulcers through the combination of drugs, pressure therapy, and surgical treatment. Budd-Chiari syndrome is a rare syndrome characterized by portal hypertension and/or inferior vena cava syndrome. Treatment of Budd-Chiari syndrome includes anticoagulation, thrombolysis, angioplasty, stenting, transjugular intrahepatic portosystemic shunt, and liver transplantation. This article reports an elderly female patient with recurrent ulceration of both lower extremities that healed poorly after long-term dressing and skin grafting. During further examination, she was found to have Budd-Chiari syndrome. Through multidisciplinary treatment, which includes removing the inferior vena cava stenosis and implanting the ulcer wound, the ulcer wounds then healed.

Background Joint contracture is the major clinical complication in burn patients, especially, the severe burn patients. This study aimed to investigate the number and severity of joint contractures in patients with burns affecting greater than or equal to 50% of the total body surface area (TBSA) undergoing early rehabilitation in a burn intensive care unit (BICU). Methods We analyzed burn patients with burns affecting greater than or equal to 50% of the TBSA admitted to a BICU who received early rehabilitation within 7 days post-injury from January 2011 to December 2015. Demographic and medical information was collected. The range of motion (ROM) of different joints was measured 1 month post-admission. Spearman’s correlation coefficient and logistic regression analysis was used to determine predictors of the presence and severity of contractures. Result The average affected TBSA of the included burn patients was 67.4%, and the average length of stay in the BICU was 46.2 ± 28.8 days. One hundred and one of 108 burn patients (93.5%) developed at least one joint contracture. The ROM in 67.9% of the affected joints was mildly limited. The majority of contractures in severe burn patients were mild (37.7%) or moderate (33.2%). The wrist was the most commonly affected joint (18.2%), followed by the shoulder, ankle, hip, knee, and elbow. A predictor of the presence of contractures was the length of hospital stay (p = 0.049). The severe contracture was related to the area of full-thickness burns, the strict bed rest time, and the duration of rehabilitation in BICU. The length of rehabilitation stay (days) in patients with moderate contracture is 54.5% longer than that in severe contracture (p = 0.024) Conclusion During the long stay in BICU, the length of rehabilitation stay in a BICU could decrease the severity of contractures from severe to moderate in the patients with equal to 50% of the TBSA. Hence, this research reveals the important role of early rehabilitation interventions in severe burn patients.

Patients with extensive deep burns usually experience infections and organ dysfunction. Proactive and effective wound repair is key to treatment. If large wounds remain open, systemic infection and multiple organ dysfunction syndrome can occur, threatening the lives of patients. Current wound repair methods include skin grafts, flap repair, negative-pressure wound therapy, and cellular and/or tissue-based products. For deep, complex burn wounds, a single form of treatment is usually ineffective. This article reports a rare case of burn wound repair. The patient was burned by a charcoal flame on multiple parts of his body after carbon monoxide poisoning. Pneumothorax and acute renal failure occurred after the injury, accompanied by multiple osteonecroses of the trunk and lower limbs. A multidisciplinary team formulated an individualized treatment plan; the diverse treatments included closed chest drainage, continuous renal replacement therapy, infection control, analgesia, wound debridement, negative-pressure wound therapy, cellular and/or tissue-based products, autologous dermal scaffold graft, skin grafts, flap transposition, platelet-rich plasma, and rehabilitation, which ultimately saved the patient's life and led to healing of all the wounds.

The Meek technique is currently a key method for treating wounds in severely burned patients. The survival rate of skin grafts is an important factor affecting the success rate of treatment. The purpose of this study was to investigate the effect of the preoperative prognostic nutritional index (PNI) on the survival rate of skin grafts in patients treated with the Meek technique in the early stage of severe burns. We retrospectively analyzed the data of severely burned patients who were treated at the burn center between January 2013 and December 2019 and met the inclusion criteria. The albumin (ALB) level and lymphocyte count obtained 1 day before the operation was used to calculate the preoperative PNI (PNI = serum ALB level [g/L] + 5 × total number of peripheral blood lymphocytes [×109/L]). According to the survival rates of skin grafts 14 days after the operation, patients with severe burns were divided into a group with good skin graft survival (survival rate ≥75%, abbreviated as group G) and a group with poor skin graft survival (survival rate .05). The total burned surface area, burn index, platelet-to-lymphocyte ratio, preoperative platelet count, operative time, total protein, albumin level, globulin level, and PNI were the risk factors affecting the survival of Meek grafts. The burn index was an independent risk factor for poor skin graft survival (odds ratio [OR]: 1.049, 95% confidence interval [CI]: 1.020–1.079; P < .05). The preoperative PNI was a protective factor against poor skin graft survival (OR: 0.646, 95% CI: 0.547–0.761; P < .05). The ROC curve determined that the optimal cut-off value for the preoperative PNI was 34.98. There were 59 cases with PNI > 34.98 (the high PNI group) and 62 cases with PNI < 34.98 (the low PNI group). The survival rate of skin grafts in patients with a high PNI was generally significantly higher than that of patients with a low preoperative PNI (P < .05). Five (8.47%) patients in the high PNI group died, compared with 16 (25.8%) patients in the low PNI group. The difference in the mortality rate between the two groups was significant (P < .05). Preoperative PNI can be used as a predictor of the survival rate of skin grafts in patients treated with the Meek technique in the early stage of severe burns.

Modified Meek micrografting is a common method for treating severe burn patients. This study was to analyze the factors affecting the survival of modified Meek micrografting, thereby improving the survival rate of skin grafts. Eighty-three patients who underwent modified Meek micrografting were analyzed. According to the survival rate of skin graft after operation, the patients were divided into good skin survival group (GSSG, survival rate ≥ 70%, 47 cases) and poor skin survival group (PSSG, survival rate < 70%, 36 cases). The baseline data, surgical information, perioperative laboratory indicators, and prognosis of the patients were statistically analyzed. The univariate analysis and repeated measurement showed the burn severity, Meek skin graft area, duration of anesthesia, the postoperative sepsis shock, the mortality, the neutrophils percentage on the third day after surgery (NEU3), and the growth rate of neutrophils percentage from the first to third day after surgery (NEU3-1%) in the GSSG were significantly lower than those in the PSSG, whereas the perioperative average albumin levels and the perioperative average pre-albumin levels were higher. Receiver operating characteristic curve showed that the NEU3 had a good predictive value for the survival of skin slices. Maintaining perioperative albumin levels at a high level, controlling perioperative infection, and shortening the operation time as much as possible may improve the survival rate of modified Meek micrografting.

COVID-19 is spreading almost all over the world at present, which is caused by the 2019 novel coronavirus (2019-nCoV). It was an epidemic firstly in Hubei province of China. The Chinese government has formally set COVID-19 in the statutory notification and control system for infectious diseases according to the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases. China currently is still struggling to respond to COVID-19 though intensive actions with progress made. The Burn Department of our hospital is one of sections with the highest infectious risk of COVID-19. Based on our own experience and the guidelines on the diagnosis and treatment of COVID-19 (7th Version) with other regulations and literature, we describe our experience with suggestions for medical practices for burn units during the COVID-19 outbreak. We hope these experiences and suggestions benefit our international colleagues during the pandemic of the COVID-19.

COVID-19 pandemic is sweeping the globe. Any outpatient or new inpatient especial in burn department during the pandemic should be as a potential infectious source of COVID-19. It is very important to manage the patients and wards carefully and correctly to prevent epidemic of the virus in burn centers. This paper provides some strategies regarding management of burn ward during the epidemic of COVID-19 or other respiratory infectious diseases.

Autophagy is a highly conserved self-protection mechanism that plays a crucial role in cardiovascular diseases. Cardiomyocyte hypoxic injury promotes oxidative stress and pathological alterations in the heart, although the interplay between these effects remains elusive. The transient receptor potential vanilloid 1 (TRPV1) ion channel is a nonselective cation channel that is activated in response to a variety of exogenous and endogenous physical and chemical stimuli. Here, we investigated the effects and mechanisms of action of TRPV1 on autophagy in hypoxic cardiomyocytes. In this study, primary cardiomyocytes isolated from C57 mice were subjected to hypoxic stress, and their expression of TRPV1 and adenosine 5′-monophosphate-activated protein kinase (AMPK) was regulated. The autophagy flux was assessed by Western blotting and immunofluorescence staining, and the cell viability was determined through Cell counting kit-8 assay and Lactate dehydrogenase assays. In addition, the calcium influx after the upregulation of TRPV1 expression in cardiomyocytes was examined. The results showed that the number of autophagosomes in cardiomyocytes was higher under hypoxic stress and that the blockade of autophagy flux aggravated hypoxic damage to cardiomyocytes. Moreover, the expression of TRPV1 was induced under hypoxic stress, and its upregulation by capsaicin improved the autophagy flux and protected cardiomyocytes from hypoxic damage, whereas the silencing of TRPV1 significantly attenuated autophagy. Our observations also revealed that AMPK signaling was activated and involved in TRPV1-induced autophagy in cardiomyocytes under hypoxic stress. Overall, this study demonstrates that TRPV1 activation mitigates hypoxic injury in cardiomyocytes by improving autophagy flux through the AMPK signaling pathway and highlights TRPV1 as a novel therapeutic target for the treatment of hypoxic cardiac disease.

Induced autophagy is protective against myocardial hypoxia/ischemia (H/I) injury, but evidence regarding the extent of autophagic clearance under H/I and the molecular mechanisms that influence autophagic flux has scarcely been presented. Here, we report that CD38 knockout improved cardiac function and autophagic flux in CD38–/– mice and CD38–/– neonatal cardiomyocytes (CMs) under H/I conditions. Mechanistic studies demonstrated that overexpression of CD38 specifically downregulated the expression of Rab7 and its adaptor protein pleckstrin homology domain-containing protein family member 1 (PLEKHM1) through nicotinamide adenine dinucleotide (NAD)-dependent and non-NAD-dependent pathways, respectively. Loss of Rab7/PLEKHM1 impaired the fusion of autophagosomes and lysosomes, resulting in autophagosome accumulation in the myocardium and consequent cardiac dysfunction under H/I conditions. Thus, CD38 mediated autophagic flux blockade and cardiac dysfunction in a Rab7/PLEKHM1-dependent manner. These findings suggest a potential therapeutic strategy involving targeted suppression of CD38 expression., Graphical Abstract CD38 inhibits transcription of the Plekhm1 gene and Rab7 gene. CD38 mediates autophagic flux blockade and cardiac dysfunction in a Rab7/PLEKHM1-dependent manner.

Mechanical barriers play a key role in maintaining the normal function of the intestinal mucosa. The barrier function of intestinal epithelial cells is significantly damaged after severe hypoxia. However, the molecular mechanisms underlying this hypoxia-induced damage are still not completely clear. Through the establishment of an in vitro cultured intestinal epithelial cell monolayer model (Caco-2), we treated cells with hypoxia or drugs (Jasplakinolide and Latrunculin A (LatA)) in order to detect changes in the transepithelial electrical resistance (TER), the expression of the cellular tight junction (TJ) proteins zonula occludens-1 (ZO-1) and occludin, the distribution of F-actin, the ratio of F-actin/G-actin content, and the expression of the cofilin protein. The results showed that hypoxia and drug treatment could both induce a significant reduction in the TER of the intestinal epithelial cell monolayer and a significant reduction in the expression of the ZO-1 and occludin protein. Hypoxia and LatA could cause a significant reduction in the ratio of F-actin/G-actin content, whereas Jasplakinolide caused a significant increase in the ratio of F-actin/G-actin content. After hypoxia, cofilin phosphorylation was decreased. We concluded that the barrier function of the intestinal epithelial cell monolayer was significantly damaged after severe burn injury. The molecular mechanism might be that hypoxia-induced F-actin depolymerization, and an imbalance between F-actin and G-actin through cofilin activation resulting in reduced expression and a change in the distribution of cellular TJ proteins.

Objective This study aims to clarify whether the effect of intralesional triamcinolone acetonide injection during the early stage of scarring differs from the static stage, which still remains unclear. Methods A total of 108 patients with pathological scars were enrolled in this study and were divided into 2 groups according to the time of first treatment after injury: the early stage group(≤6 months after injury) and the static stage group(>6 months after injury). Patients of both groups were then treated with intralesional triamcinolone acetonide injection. The Vancouver scar scale was adopted for the evaluation of scars, and a durometer was utilized for the measurement of the hardness of the scar. The visual analog scale was adopted for the assessment of patients' subjective feelings (pruritus and pain). In the meantime, adverse drug reactions were also recorded. Results After intralesional injection of triamcinolone acetonide, most of the hypertrophic scars and keloids improved in color, thickness, softness, and vascular distribution. The hardness of scars improved significantly. The overall efficacy of the static stage group was superior to the early stage group. Most patients, after the injection of triamcinolone acetonide, had significant alleviation or even total loss of cicatricial pain and pruritus. Conclusions This study demonstrates that the treatment efficacy was better when applied during the static stage of pathological scarring rather than the early stage, which might be due to macrophages and their released cytokines. This study provides new clinical evidence for optimizing drug therapy of pathological scars.

Cutaneous diffuse large B-cell lymphoma (DLBCL) usually manifests as papules, nodules, or plaques. A rare case of a patient with a chronic skin ulcer and signs and symptoms of infection, including fever and large amounts of yellow wound exudate, is presented. Fifteen (15) months before diagnosis, a 43-year-old otherwise healthy man noted soreness without apparent cause in his upper chest and a palpable 2 cm x 2 cm focal lump. The patient developed frequent fevers, and the lump enlarged over time, producing purulent exudate. For 14 months, the patient was examined and treated at 5 hospitals, but biopsies, smears, cultures, and various types of nucleic acid testing were negative. Antibiotics to treat the suspected but nonclassified infection were ineffective. Ultimately, debridement and pathological examination of necrotic tissue from the deep sinus revealed DLBCL. The patient was provided chemotherapy, surgical debridement, and negative pressure wound therapy. Wounds started to reduce in size once chemotherapy was initiated. The wound was surgically closed with a split-skin graft, and the patient was discharged 93 days following admission to the authors' facility. This case illustrates the possibility of cutaneous DLBCL in patients with chronic skin ulcers and infectious manifestation that do not respond to antibiotic therapy. Prompt deep tissue debridement and pathological examination of deep tissue will help confirm the presence of cutaneous DLBCL and guide required chemotherapy.

Background/Aims: The phosphatidylinositol-3-kinase -AKT (PI3K-AKT) is an important intracellular signal pathway in regulating cell proliferation, differentiation and apoptosis. In previous studies, we’ve demonstrated that PI3K–AKT pathway protects cardiomyocytes from ischemic and hypoxic apoptosis through mitochondrial function. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis via PI3K-AKT pathway remain ill-defined. Here, we addressed this question. Methods: Cardiomyocytes were exposed to hypoxia, with/without different inhibitors and then protein levels were assessed by Western blotting. Results: We found that the PI3K–AKT pathway was activated in cardiomyocytes that were exposed to hypoxia. Moreover, the phospho-AKT (pAKT) translocated from cytosol to mitochondria via mitochondrial adenosine triphosphate-dependent potassium (mitoKATP), leading to an increase in cytochrome c oxidase (CcO) activity to suppress apoptosis. On the other hand, the mitoKATP specific blocker, 5-hydroxydecanote (5-HD), or suppression of CcO using siRNA, inhibited the pAKT mitochondrial translocation to maintain the CcO activity, resulting in mitochondrial dysfunction and cellular apoptosis induced by hypoxia. Conclusion: These findings suggest that the anti-apoptotic effect of the PI3K-AKT pathway through pAKT translocation to mitochondrial via mitoKATP may be conducted through modification of CcO activity.

Both cell migration and proliferation are indispensable parts of reepithelialization during skin wound healing, which is a complex process for which the underlying molecular mechanisms are largely unknown. Here, we identify a novel role for microtubule-associated protein 4 (MAP4), a cytosolic microtubule-binding protein that regulates microtubule dynamics through phosphorylation modification, as a critical regulator of epidermal wound repair. We showed that MAP4 phosphorylation was induced in skin wounds. In an aberrant phosphorylated MAP4 mouse model, hyperphosphorylation of MAP4 (S737 and S760) accelerated keratinocyte migration and proliferation and skin wound healing. Data from both primary cultured keratinocytes and HaCaT cells in vitro revealed the same results. The promigration and proproliferation effects of MAP4 phosphorylation depended on microtubule rearrangement and could be abolished by MAP4 dephosphorylation. We also identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in keratinocytes. Our findings provide new insights into the molecular mechanisms underlying wound-associated keratinocyte migration and proliferation and identify potential targets for the remediation of defective wound healing.

Tight junction barrier is critical to intestinal homeostasis. Applying antibiotics to treat infections is common in clinical practice, which may affect intestinal microbiota. Intestinal microbiota dysbiosis is involved in the occurrence of some gastrointestinal diseases. Therefore, this study was aimed to investigate the influence of antibiotics on intestinal tight junction barrier and the possible underlying mechanisms. Healthy adult female C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail for 14 days. 16S rDNA Illumina sequencing and headspace gas chromatography-mass spectrometry (HS-GC/MS) were respectively used to analyze microbial community and to detect short-chain fatty acids (SCFAs) contents. In vivo intestinal paracellular permeability to fluorescein isothiocyanate-dextran (FITC-dextran) was measured. Protein expression was determined by immunoblotting. Immunofluoresence was applied to observe the distributions of ZO-1, LC3B and ASC. Antibiotics remarkably altered intestinal microbiota composition in healthy mice, accompanying reduced SCFAs' concentrations. In addition, the intestinal tight junction barrier was disrupted by antibiotic treatment, as evidenced by increased intestinal paracellular permeability to FITC-dextran, decreased tight junction protein expressions, and disrupted ZO-1 morphology. Furthermore, NLRP3 inflammasome and autophagy were activated by antibiotic treatment. In conclusion, intestinal epithelial tight junction barrier dysfunction induced by antibiotics is associated with intestinal microbiota dysbiosis, activated NLRP3 inflammasome and autophagy in mice.

BackgroundTumor necrosis factor receptor-associated protein 1 (TRAP1) plays a protective effect in hypoxic cardiomyocytes, but the precise mechanisms are not well clarified. The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.MethodsIn this study, the effects of TRAP1 and cytochrome c oxidase subunit II (COXII) on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.ResultsHypoxia induced cardiomyocyte apoptosis, and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia. Conversely, TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes. Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXII overexpression, whereas COXII knockdown reduced the antiapoptotic function induced by TRAP1 overexpression. Additionally, changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm, as well as reactive oxygen species production, were found to be correlated with the changes in apoptosis.ConclusionsThe current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXII, in which reactive oxygen species presents as an important component.

Table S1. Range of motion severity ratings by joint muscle action. (PDF 125 kb)

Maladaptive cardiac metabolism is a common trigger of cardiac lipid accumulation and cardiac injury under serious burn challenge. Adipose triglyceride lipase (ATGL) is the key enzyme that catalyzes triglyceride hydrolysis; however, its alteration and impact on cardiac function following serious burn injury are still unknown. Here, we found that the cardiac fatty acid (FA) metabolism increased, accompanied by augmented FA accumulation and ATGL expression, after serious burn injury. We generated heterozygous ATGL knockout and heterozygous cardiac-specific ATGL overexpression thermal burn mice. The results demonstrated that partial loss of ATGL could not relieve burn-induced cardiac lipid accumulation and cardiac injury, possibly due to the suppression of cardiac FA metabolism plus insufficient compensatory glucose utilization. In contrast, cardiac-specific overexpression of ATGL alleviated cardiac lipid accumulation and cardiac injury following burn challenge by switching the substrate preference from FA towards increased glucose utilization. The underlying mechanism was possibly related to increased glucose transporter-1 expression and reduced cardiac lipid accumulation induced by ATGL overexpression. Our data first demonstrated that elevated cardiac ATGL expression after serious burn injury is an adaptive, albeit insufficient, response to compensate for the increase in energy consumption and that further overexpression of ATGL is beneficial for ameliorating cardiac injury, indicating its therapeutic potential.

The proliferation and migration of intestinal epithelial cell is important to the barrier integrity of intestinal epithelium. Cucurbitacin E (CuE) is one of the tetracyclic triterpenoids extracted from the cucurbitaceae that has been shown to inhibit cancer cell growth, tumor angiogenesis and inflammatory response. Nevertheless, the role of Cucurbitacin E in regulating the proliferation and migration of intestinal epithelial cells remain unclear.. In this study, the human intestinal epithelial cell line Caco-2 was treated with CuE and the effects of CuE on cell cycle, proliferation, migration and actin dynamics in Caco-2 cells were investigated successively. We found that CuE significantly inhibited the cell proliferation and migration, inducing the cell cycle arrest in G2/M phase and disrupting the actin dynamic balance in Caco-2 cells. Finally, we showed that CuE inhibited cofilin phosphorylation by suppressing the phosphorylation of both LIM kinase (LIMK)1 and LIMK2 in vitro, resulting in the activation of cofilin, which is closely associated with cell proliferation and migration. Therefore, our studies provided the first evidence that CuE inhibited the proliferation and migration of intestinal epithelial cells via activating cofilin, and CuE is a potential candidate in intestinal disease therapy.

1. After a severe burn, a marked decrease in myocardial blood flow results in ischaemic and hypoxic injury, which subsequently leads to apoptosis or necrosis. Phosphatidylinositol 3-kinase (PI3-K)/Akt is an important intracellular signal transduction molecule that regulates cell proliferation, differentiation, glucose metabolism and migration. However, the function and mechanisms of the PI3-K-Akt pathway in cardiomyocyte apoptosis after a burn remain unclear. 2. In the present study, an in vivo rat model of burn injury and an in vitro hypoxic model using rat cardiomyocytes were established. In burned rats, the expression of PI3-K and phosphorylated (p-) Akt expression increased, as did myocardial apoptosis. Inhibition of the PI3-K-Akt pathway with 1.4 mg/kg LY294002 caused a significant increase in the myocardial apoptotic index compared with hypoxia alone in the in vivo model. 3. Cardiomyocytes cultured under hypoxic conditions exhibited increased apoptosis, decreased cell viability, enhanced caspase 3 activity, a decreased mitochondrial membrane potential, increased cytoplasmic calcium transients and increased p53 and Bax mRNA expression. Pretreatment with 50 mumol/L LY294002 significantly enhanced all these negative indicators compared with hypoxia alone. In contrast, pretreatment of cells with 200 ng/mL insulin-like growth factor-1, an activator of PI3-K-Akt, significantly ameliorated the effects of hypoxia, although control levels were not reached. 4. These findings indicate that activation of the PI3-K-Akt pathway induced by ischaemia and hypoxia after a severe burn can protect cardiomyocytes from apoptosis. This anti-apoptotic effect is most likely mediated via the mitochondria and changes in p53 and Bax gene expression, intracellular [Ca(2+)] and caspase 3 activity.

This article reports the successful experience of integration of burn treatment and rehabilitation for a child suffering from 91% TBSA flame burn injury (with 60% TBSA full-thickness injury, 30% TBSA deep partial-thickness injury, and 1% TBSA superficial partial-thickness injury), severe inhalation injury, severe burn shock, stress ulcer, gastrointestinal bleeding and atelectasis of the right upper lung. The patient was given effective fluid infusion against shock, treatment for gastrointestinal bleeding, and other effective supportive treatment for functions of various organs after being admitted to our burn ward. When vital signs became stable at 30 hours post injury, bedside rehabilitation was begun. On post injury day (PID) 4, escharectomy was performed for both lower limbs, followed by microskin grafting and allogeneic skin covering. On PID 10, invasive infection of multi-drug resistant bacteria was found with accompanied high fever, and at the same time allograft began to disintegrate, with dissolution of large area of eschar, leading to a raw surface reaching 86% TBSA. Following debridement, dressing, application of compound polymyxin B ointment, temporary covering of wounds with porcine acellular dermal matrix, adjustment of antibiotics, patient's condition was finally stabilized. From PID 28 on, split-thickness skin grafting was conducted 7 times, and the raw surface of 75% TBSA involving the upper and lower limbs and trunk was successfully covered. At the same time, our rehabilitation team launched comprehensive rehabilitation measures comprising active exercise, occupational therapy, prevention of scar formation, organ function training and psychological intervention. Finally, the patient was able to walk unaided and fed herself when the wounds were almost entirely healed in 3 months after injury. Oriented forwards functional rehabilitation, strong cooperation between team members, and synchronous effective implementation of burn treatment and rehabilitation in the whole process are the keys to achieve successful integration of burn treatment and rehabilitation of this child.

1. Astragaloside IV (AST-IV) is purified from a natural plant product. Previous studies have shown that AST-IV has anti-oxidant activity. In the present study, we investigated the effect and mechanism of action AST-IV on rat cardiomyocytes subjected to hypoxic conditions (up to 12 h). 2. Cardiomyocytes were prepared from neonatal rats and cultured under normoxic or hypoxic conditions in the absence or presence of AST-IV (12.5, 25 or 50 microg/mL). Cell viability, malondialdehyde (MDA) levels, activity and expression of superoxide dismutase (SOD)-1 (mRNA and protein levels determined by reverse transcription-polymerase chain reaction and western blotting, respectively) and reactive oxygen species (ROS; determined by 2',7'-dichlorodihydrofluorescein diacetate) were investigated under these culture conditions. Intracellular localization of AST-IV was tested using fluorescein isothiocyanate-labelled AST-IV. 3. Hypoxic culture reduced the viability of cardiomyocytes, which was improved following treatment with 25 or 50 microg/mL AST-IV. Under hypoxic conditions, MDA levels were double those under control conditions. Astragaloside IV (25 and 50 microg/mL) dose-dependently reduced the increase in MDA seen in hypoxic cardiomyocytes. 4. Fluorescein isothiocyanate-labelled AST-IV entered cardiomyocytes and was localized mainly within the cytoplasm. 5. Under hypoxic conditions, SOD-1 activity was decreased, but mRNA and protein expression increased, compared with normoxia. Following treatment with 25 microg/mL AST-IV, SOD-1 activity and expression were increased under both normoxic and hypoxic conditions. The ROS scavenging effect of AST-IV was abolished in the presence of the SOD inhibitor sodium diethyl dithiocarbamate (25 micromol/L). 6. These in vitro results show that AST-IV protects cardiomyocytes from oxidative stress-mediated injury under hypoxic conditions. A major part of this action is achieved by upregulation of SOD-1 content and activity within the cell cytoplasm.