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DECLARATION OF INTEREST: The authors have no conflicts of interest.
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Nocardiose , Úlcera , Humanos , Cicatrização , Nocardiose/complicações , Nocardiose/diagnósticoRESUMO
Chronic wounds have become one of the major issues in medicine today, the treatments for which include dressing changes, negative pressure wound therapy, hyperbaric oxygen, light irradiation, surgery and so forth. 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 (810 nm) irradiation on chronic wounds. Eighty-nine 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 min 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.
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Terapia a Laser , Terapia com Luz de Baixa Intensidade , Humanos , Cicatrização/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Estudos Retrospectivos , DorRESUMO
ABSTRACT: 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.
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Queimaduras/etiologia , Intoxicação por Monóxido de Carbono/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Adulto , Coma/etiologia , Desbridamento/métodos , Incêndios , Humanos , Masculino , Pneumotórax/etiologia , Pneumotórax/fisiopatologia , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologiaRESUMO
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.
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Autofagia/genética , Traumatismos Cardíacos/genética , Proteínas Quinases/genética , Canais de Cátion TRPV/genética , Quinases Proteína-Quinases Ativadas por AMP , Animais , Cálcio/metabolismo , Capsaicina/farmacologia , Sobrevivência Celular/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Traumatismos Cardíacos/patologia , Humanos , Hipóxia/genética , Hipóxia/metabolismo , Hipóxia/patologia , Camundongos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais/genéticaRESUMO
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.
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Apoptose , Hipóxia Celular , Fosfatidilinositol 3-Quinases/metabolismo , Canais de Potássio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Células Cultivadas , Cromonas/farmacologia , Ácidos Decanoicos/farmacologia , Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hidroxiácidos/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Morfolinas/farmacologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Canais de Potássio/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Hydrofluoric acid (HF) is a strongly corrosive, highly toxic, and highly dangerous mineral acid. Burns with over 1% TBSA caused by anhydrous HF can lead to deep tissue damage, hypocalcemia, poisoning, and even death. In recent years, HF has become one of the most common substances causing chemical burns and ranks as the leading cause of death from chemical burns. Herein, we report a rare case with 91% TBSA burns caused by 35% HF. The patient developed complications such as shock, severe hypocalcemia, metabolic acidosis, and respiratory failure. Multidisciplinary team consultation (burns, respiratory medicine, nephrology, infectious disease, and pharmacy) was performed immediately after admission. An individualized diagnosis and treatment plan were developed for the patient. The patient was given intensive care, blood volume monitoring, tracheotomy, fluid resuscitation, continuous blood purification, anti-infective and analgesic treatments, intravenous and percutaneous calcium supplementation, early rehabilitation training, psychological rehabilitation, and other treatments. To prevent the wound from deepening, large-area debridement and skin grafting were performed early after the injury. A large dose of 10% calcium gluconate was injected into the patient in divided doses, and the wound was continuously treated with wet dressings. Multiple surgical debridements, negative pressure wound treatment, biological dressings, and Meek skin grafting were performed. After most of the wounds (approximately 85% TBSA) healed, the patient was discharged from the hospital and continued to undergo dressing changes at a local hospital. The patient was followed up 3 months after discharge. All the wounds healed well, and the patient basically regained functional independence in daily life.
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Queimaduras Químicas , Ácido Fluorídrico , Humanos , Queimaduras Químicas/terapia , Queimaduras Químicas/etiologia , Masculino , Transplante de Pele , Desbridamento , Gluconato de Cálcio/uso terapêutico , AdultoRESUMO
BACKGROUND: Severe burns can readily induce gastric and duodenal mucosal erosions and superficial ulcers. In severe cases, haemorrhage or perforation of peptic ulcers might occur, threatening the lives of patients. At present, gastrointestinal haemorrhage after burns is treated mainly with drugs and gastrointestinal endoscopy. However, multidisciplinary treatment of gastroscopy combined with vascular embolization is rare. CASE: A boy aged 3 years and 4 months was admitted to the hospital, scalded by boiling water on multiple parts of the body. On the 8th day after the injury, the patient continuously produced a large amount of tarry black stool, and the faecal occult blood test was positive. Haemostatic drug treatment was ineffective, and severe shock and disseminated intravascular coagulation (DIC) occurred. Under the guidance of a multidisciplinary team (MDT), a gastroscopy examination was performed and showed bleeding from a duodenal bulb ulcer. Due to a small intestinal lumen and thin intestinal wall, bleeding could not be controlled by gastroscopy. However, the bleeding point was clarified by gastroscopy and then gastroduodenal artery embolization was performed efficiently. No active gastrointestinal bleeding was observed after the surgery. The patient was followed for 6 months after discharge, and no gastrointestinal haemorrhage recurred. CONCLUSIONS: This is a rare case of acute massive upper gastrointestinal bleeding secondary to post-burn stress in paediatric patients. For paediatric patients who cannot be treated by endoscopy, transcatheter embolization may be safer and more effective for achieving haemostasis. Through the collaboration of the MDT, gastroscopy combined with interventional embolization was performed, which successfully stopped the massive bleeding and saved the child`s life, making it worthy of clinical reference.
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Embolização Terapêutica , Hemorragia Gastrointestinal , Masculino , Humanos , Criança , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , EstômagoRESUMO
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.
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Queimaduras , Queimaduras/cirurgia , Humanos , Tempo de Internação , Estudos Retrospectivos , Pele , Transplante de Pele/métodosRESUMO
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 χâ2 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.
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Perda Sanguínea Cirúrgica , Queimaduras , Adulto , Queimaduras/cirurgia , Humanos , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
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.
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Queimaduras , Sepse , Humanos , Prognóstico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Curva ROC , Pró-Calcitonina , BiomarcadoresRESUMO
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.
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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 <75%, abbreviated as group P). Receiver-operating characteristic (ROC) curves and univariate and multivariate analyses were used to evaluate the predictive value of the preoperative PNI for the prognosis of patients treated with the Meek technique. One hundred and twenty-one patients were enrolled in this study. Groups G (n = 66 cases) and P (n = 55 cases) did not have significant differences in age, sex, and body mass index (P > .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.
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Queimaduras/cirurgia , Sobrevivência de Enxerto , Avaliação Nutricional , Transplante de Pele/métodos , Adolescente , Adulto , Idoso , Unidades de Queimados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.
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Queimaduras/cirurgia , Transplante de Pele/métodos , Sobrevida , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/métodos , Resultado do TratamentoRESUMO
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.
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Apoptose , Queimaduras/complicações , Mitocôndrias Cardíacas/fisiologia , Isquemia Miocárdica/prevenção & controle , Miócitos Cardíacos , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Queimaduras/enzimologia , Queimaduras/patologia , Queimaduras/fisiopatologia , Cálcio/metabolismo , Caspase 3/metabolismo , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Feminino , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Morfolinas/farmacologia , Isquemia Miocárdica/enzimologia , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinases/biossíntese , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p53/biossínteseRESUMO
Apoptosis plays a crucial role in maintaining the structural and functional integrity of the intestinal epithelial barrier. Autophagy mediates injury to and repair of the intestinal epithelial barrier through multiple pathways in pathophysiological conditions. Our earlier study has found that cucurbitacin E (CuE) regulates the proliferation, migration, and permeability of human intestinal epithelial cells (IECs); however, its effects and mechanisms on apoptosis and autophagy are still unclear. This study reported CuE induced apoptosis and promoted autophagy of IECs in a concentration-dependent manner. The results showed that CuE could inhibit the expression of apoptosis-related protein Bcl-2 and drove activation of caspase-3 and cleavage of its substrate poly (ADP-ribose) polymerase. CuE also facilitated the expression of endoplasmic reticulum stress-related proteins, CHOP and Grp78, and autophagy-related proteins, Beclin1 and LC3, while inhibiting the phosphorylation of AKT and mammalian target of rapamycin (mTOR). An autophagy inhibitor, 3-methyladenine, reduced CuE-induced apoptosis. These results suggest that CuE may induce apoptosis and autophagy in IECs via the PI3K/AKT/mTOR signaling pathway and that autophagy following endoplasmic reticulum stress participates in the pro-apoptotic process induced by CuE.
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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.
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Queimaduras/terapia , Infecções por Coronavirus , Atenção à Saúde/organização & administração , Controle de Infecções/métodos , Pandemias , Pneumonia Viral , COVID-19 , HumanosRESUMO
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.
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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.
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Unidades de Queimados/organização & administração , Queimaduras/terapia , Infecções por Coronavirus , Controle de Infecções/organização & administração , Pandemias , Pneumonia Viral , COVID-19 , Atenção à Saúde/organização & administração , HumanosRESUMO
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.
Assuntos
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Saponinas/farmacologia , Superóxido Dismutase/genética , Triterpenos/farmacologia , Animais , Animais Recém-Nascidos , Hipóxia Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citoproteção/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Modelos Biológicos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacocinética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Triterpenos/farmacocinética , Regulação para Cima/efeitos dos fármacosRESUMO
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.