Objective To investigate the protective effect of resveratrol (RSV) on improving cognitive function in severely burned rats and its possible mechanism. Methods 18 male SD rats aged 18-20 months were randomly divided into 3 groups: control group, model group and RSV group, with 6 rats in each group. After successful modeling, the rats in RSV group were gavaged once daily with RSV (20 mg/kg). Meanwhile, the rats in control group and model group were gavaged once daily with an equal volume of sodium chloride solution. After 4 weeks, the cognitive function of all rats was estimated by Step-down Test. The concentration of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) protein in serum of rats were detected by ELISA. The expression of IL-6, TNF-α mRNA and protein were estimated by real-time PCR and Western blotting. The apoptosis of hippocampal neurons was tested by terminal deoxynuclectidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). The expression of nuclear transcription factor-κB (NF-κB)/c-Jun N-terminal kinase (JNK) pathway-related proteins in hippocampus were assessed by Western blotting. Results Compared with the rats in model group, rats in RSV group exhibited improved cognitive function. Consistently, the rats in RSV group had a reduced concentration of TNF-α and IL-6 in serum, decreased mRNA and protein expressions of TNF-α and IL-6 in hippocampus, and decreased apoptosis rate and relative expression of p-NF-κB p65/NF-κB p65 and p-JNK/JNK in hippocampal neurons. Conclusion RSV alleviates inflammatory response and hippocampal neuronal apoptosis by inhibiting NF-κB/JNK pathway, thereby improving cognitive function in severely burned rats.
Resveratrol/pharmacology* ; Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Burns/drug therapy* ; Cognition/drug effects* ; Hippocampus/metabolism* ; MAP Kinase Signaling System ; NF-kappa B/metabolism* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-6/blood* ; Neurons/drug effects* ; Apoptosis

Wound is the most fundamental issue of burn injury, and its repair depends not only on effective wound treatment, but also on the good nutritional status of burned patients. Nutrition support is an important means to improve the nutritional status of patients and promote wound healing, and how to make it match the metabolism of burn wounds is a difficult task of nutrition therapy. In this paper, we analyzed the metabolic characteristics of different stages in burn wound healing, focused on the metabolic characteristics of glucose, protein, and glutamine in these stages, and proposed a nutritional strategy that is compatible with wound healing in order to maximize the role of nutrition therapy in wound repair.
Burns/therapy* ; Glutamine ; Humans ; Nutritional Support ; Proteins/metabolism* ; Wound Healing

Objective: To investigate the effect of sedation on resting energy expenditure (REE) in patients with extremely severe burns and the choice of REE estimation formula during the treatment. Methods: A retrospective non-randomized controlled clinical study was conducted. From April 2020 to April 2022, 21 patients with extremely severe burns who met the inclusion criteria and underwent mechanical ventilation treatment were admitted to the Department of Burn and Wound Repair of Second Affiliated Hospital of Zhejiang University School of Medicine, including 16 males and 5 females, aged 60 (50, 69) years. Early anti-shock therapy, debridement, skin transplantation, nutritional support, and other conventional treatments were applied to all patients. Patients were sedated when they had obvious agitation or a tendency to extubate, which might lead to aggravation of the disease. REE measurement was performed on patients using indirect calorimetry on post-injury day 3, 5, 7, 9, 11, 14 and every 7 days thereafter until the patient died or being successfully weaned from ventilator. Totally 99 times of measurements were carried out, of which 58 times were measured in the sedated state of patients, and 41 times were measured in the non-sedated state of patients. The age, weight, body surface area, residual wound area, post-injury days of patients were recorded on the day when REE was measured (hereinafter briefly referred to as the measurement day). The REE on the measurement day was calculated with intensive care unit conventional REE estimation formula Thumb formula and special REE estimation formulas for burns including the Third Military Medical University formula, the Peng Xi team's linear formula, Hangang formula. The differences between the sedated state and the non-sedated state in the clinical materials, measured and formula calculated values of REE of patients on the measurement day were compared by Mann-Whitney U test and independent sample t test. The differences between the REE formula calculated values and the REE measured value (reflecting the overall consistency) in the sedated state were compared by Wilcoxon signed rank-sum test. The Bland-Altman method was used to assess the individual consistency between the REE formula calculated value and the REE measured value in the sedated state, and to calculate the proportion of the REE formula calculated value within the range of ±10% of the REE measured value (hereinafter referred to as the accuracy rate). Root mean square error (RMSE) was used to evaluate the accuracy of the REE formula calculated value relative to the REE measured value. Results: Compared with those in the non-sedated state, there was no statistically significant change in patient's age or post-injury days on the measurement day in the sedated state (P>0.05), but the weight was heavier (Z=-3.58, P<0.01), and both the body surface area and the residual wound area were larger (with Z values of -2.99 and -4.52, respectively, P<0.01). Between the sedated state and the non-sedated state, the REE measured values of patients were similar (P>0.05). Compared with those in the non-sedated state, the REE values of patients calculated by Thumb formula, the Third Military Medical University formula, the Peng Xi team's linear formula, and Hangang formula on the measurement day in the sedated state were significantly increased (with Z values of -3.58 and -5.70, t values of -3.58 and -2.74, respectively, P<0.01). In the sedated state, compared with the REE measured value, there were statistically significant changes in REE values of patients calculated by Thumb formula, the Third Military Medical University formula, and Hangang formula on the measurement day (with Z values of -2.13, -5.67, and -3.09, respectively, P<0.05 or P<0.01), while the REE value of patients calculated by the Peng Xi team's linear formula on the measurement day did not change significantly(P>0.05). The analysis of the Bland-Altman method showed that in the sedated state, compared with the REE measured value, the individual consistency of the calculated value of each formula was good; Thumb formula and Hangang formula significantly underestimated the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of -1 463 and -1 717 kJ/d, the 95% confidence interval of -2 491 to -434 and -2 744 to -687 kJ/d, respectively), but the individual differences were small; the Third Military Medical University formula significantly overestimated the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of 3 530 kJ/d, the 95% confidence interval of 2 521 to 4 539 kJ/d), but the individual difference was small; the Peng Xi team's linear formula did not significantly overestimate the patients' REE value (with the average value of the difference between the formula calculated value and the measured value of 294 kJ/d, the 95% confidence interval of -907 to 1 496 kJ/d), while the difference standard deviation was 4 568 kJ/d, which showed a large individual difference. In the sedated state, relative to the REE measured value, the accuracy rates of REE values calculated by Thumb formula, the Third Military Medical University formula, the Peng Xi team's linear formula, and Hangang formula were 25.9% (15/58), 15.5% (9/58), 10.3% (6/58), and 15.5% (9/58), respectively, and RMSE values were 4 143.6, 5 189.1, 4 538.6, and 4 239.8 kJ/d, respectively. Conclusions: Sedative therapy leads to a significant decrease in REE in patients with extremely severe burns undergoing mechanical ventilation treatment. When REE cannot be regularly monitored by indirect calorimetry to determine nutritional support regimens, patients with extremely severe burns undergoing sedation may be prioritized to estimate REE using Thumb formula.
Burns/therapy* ; Calorimetry, Indirect ; Energy Metabolism ; Female ; Humans ; Male ; Nutritional Support ; Retrospective Studies

Burns often cause the damaged tissue to produce a large amount of exudate and the formation of blisters on the wound. The burn blister fluid contains a large number of molecules related to wound healing, which can reflect the state of local tissue microenvironment of the burn wound. Analyzing relevant information such as cellular components, signal mediators, and protein molecules in burn blister fluid is helpful to understand the local reaction and tissue microenvironment of burn wounds, and then help clinical burn treatment. In this article, by understanding the production mechanism of burn blister fluid, discussing its role in wound evaluation, and integrating the research progress of burn blister fluid in proteomics, metabolomics, cellular components, and pharmacokinetics, we propose our thoughts and prospects on the research of burn blister fluid, in order to provide assistance for clinical evaluation and treatment of burn wounds, and also provide idea for the follow-up study of burn blister fluid.
Humans ; Blister/metabolism* ; Follow-Up Studies ; Burns/metabolism* ; Exudates and Transudates/metabolism* ; Wound Healing

OBJECTIVES: To explore the forensic application value of cluster of differentiation 83 (CD83) and heat shock transcription factor 5(HSF5) in identifying antemortem and postmortem skin burns. METHODS: Through reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR), CD83 and HSF5 mRNA levels in the skin tissues of antemortem and postmortem burned mice and human samples were detected quantitatively. RESULTS: Compared with the control group and the postmortem burned group, the mRNA levels of CD83 and HSF5 in antemortem burned mice were higher. The high mRNA expressions of CD83 could be detected 96 h after death, and the mRNA expressions of HSF5 could be observed 72 h after death. Compared with undamaged skin, increased CD83 and HSF5 mRNA levels were detected in 11 out of 15 cases(P<0.05). CONCLUSIONS CD83 and HSF5 can be used in forensic practice as indicators for vital reaction in antemortem burn identification.
Animals ; Autopsy ; Burns/metabolism* ; Forensic Medicine ; Mice ; Postmortem Changes ; Skin/injuries* ; Soft Tissue Injuries

OBJECTIVES: The objective of the study was to determine whether postburn reduction of bone formation occurred earlier than 2–3 weeks after burn injury and whether that reduction was inversely related to marrow adiposity. METHODS: Using a rat model of burn injury with sacrifice at 3 days postburn, we measured serum osteocalcin, a biomarker of bone formation, as well as a regulator of glucose metabolism, and counted tibial marrow adipocytes. RESULTS: Serum osteocalcin was reduced as early as 3 days postburn, coinciding with a trend toward decline in marrow adipocyte number rather than demonstrating an inverse relationship with adipocyte count. CONCLUSIONS: Factors that may be responsible for the dissociation include lack of circulating sclerostin, previously reported, increased energy demands following burn injury, increased sympathetic tone and perhaps oxidative stress. The relationship between bone formation and marrow adiposity is complex and subject to a variety of influences.
Adipocytes ; Adiposity ; Animals ; Bone Marrow ; Burns ; Child ; Glucose ; Humans ; Metabolism ; Models, Animal ; Osteocalcin ; Osteogenesis ; Oxidative Stress ; Rats

OBJECTIVE: To investigate the effects of Coriaria Sinica Maxim's extract(CSME) on microcirculation and oxidative stress of wounds in rats with deep second-degree burn. METHODS: One hundred and eighty rats were randomly divided into normal saline group(NS), white petroleum group(WPL), silver sulfadiazine group (SSD), Coriariasinica Maxim's extract group which were divided into low dose(CSME-L),middle dose(CSME-M) and high dose(CSME-H). After anesthesia with burn instrument to burn the hair removal area of rats, these wounds were confirmed by pathological results with deep second degree burns.And then,those drugs were applied respectively on the wounds,such as NS、WPL、SSD and different concentrations of CSME. After injury at 48 h, 7 d, 14 d and 21 d,the healing rate(HR) of wound was measured, and the microvessel density (MVD), tissue moisture (TM), vascular endothelial growth factor (VEGF), model driven architecture (MDA), superoxide dismutase(SOD) and hydroxyproline(HYP) were detected, too. All pathological sections of the wound tissue were observed. RESULTS: The HR of CSME groups were obviously increased with a dose-dependent manner, which was significantly higher than that of NS and WPL (<0.05); On the 21 day, the diameter, number, distribution of the vessels and and the TM were less than other groups with a dose-dependent manner; On the 7 and 14 day after injury, CSME groups were significantly higher than the NS, WPL and SSD with a dose-dependent manner (<0.05), but, on the 21 day after injury, they were lower than NS, WPL and SSD with a dose-dependent (<0.05) manner. The levels of SOD, HYP, NO and ET in CSME groups were higher than those in other groups with dose-dependent on SOD activity, HYP, NO and ET content (<0.05), while MDA activity was weaker than other groups (<0.05). Similarly, pathological findings were also shown that CSME groups were better than other groups with a dose-dependent manner in decrease decreasing of wound repair time and hyperplasia of scar tissue. CONCLUSIONS CSME can relieve tissue edema, promote wound contraction, speed up the formation of eschar and accelerate the proliferation of granulation tissue, which are beneficial to the wound healing in the early stages. But, it can inhibit the hyperplasia of granulation tissue to prevent the excessive scar hyperplasia of burn wound in the later stages. Its mechanism is related to regulation what microcirculation, oxidativestress, NO and VEGF.
Animals ; Burns ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Hydroxyproline ; metabolism ; Malondialdehyde ; metabolism ; Microcirculation ; Oxidative Stress ; Random Allocation ; Rats ; Superoxide Dismutase ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing ; drug effects

We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease.
Adult ; Angiokeratoma ; Burns ; Cornea ; Ear ; Echocardiography ; Electrocardiography ; Exons ; Extremities ; Fabry Disease* ; Galactosidases ; Genetic Counseling ; Hematuria ; Humans ; Hypertrophy, Left Ventricular ; Informed Consent ; Male ; Metabolism ; Outpatients ; Physical Examination ; Plasma ; Proteinuria ; Thorax

OBJECTIVETo primarily evaluate the effects of ulinastatin on immune function of patients with severe burn injury.

METHODSForty patients with severe burn admitted to our ward from March 2013 to October 2015, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and ulinastatin treatment group (UT, n=20) according to the random number table and patient's consent. After admission, patients in group CT received antishock treatment, antibiotic treatment, debridement, skin grafting, and nutrition support, etc. On the basis of the above-mentioned treatment, patients in group UT received intravenous drip of ulinastatin from first day after admission twice a day, with a dosage of 8×10(5) U every time, for 7 days in addition. Peripheral venous blood samples were collected from patients in groups CT and UT on post treatment day (PTD) 1, 3, 5 and 7, respectively. Twenty healthy volunteer were selected as health control group (HC), and peripheral venous blood samples were collected on the first day of the study. Percentage of CD4(+) CD25(+) regulatory T lymphocytes (Tregs) was determined by flow cytometer. The proliferative activity of T lymphocytes was detected by microplate reader (denoted as absorbance value). Content of interleukin 2 (IL-2) in culture supernatant of T lymphocytes, and content of IL-4 and γ interferon (IFN-γ) in serum were detected by enzyme-linked immunosorbent assay. Expression of human leukocyte antigen-DR (HLA-DR) on CD14(+) monocytes was determined by flow cytometer. Data were processed with analysis of variance for repeated measurement, chi-square test, and LSD-t test.

RESULTS(1) Compared with that of volunteer in group HC, the percentage of CD4(+) CD25(+) Tregs of patients in group CT was significantly increased from PTD 1 to 7 (with t values from 13.303 to 26.043, P values below 0.01). Compared with that in group CT, the percentage of CD4(+) CD25(+) Tregs of patients in group UT was significantly decreased on PTD 5 and 7 (with t values respectively 8.317 and 15.071, P values below 0.01). (2) The proliferative activity of T lymphocytes of patients in group CT on PTD 1, 3, 5, and 7 was respectively 0.71±0.11, 0.61±0.15, 0.54±0.12, and 0.67±0.17, which was significantly lower than that in group HC (1.21±0.22, with t values from 8.686 to 11.957, P values below 0.01). The proliferative activity of T lymphocytes of patients in group UT on PTD 3, 5, and 7 were respectively 0.81±0.11, 0.85±0.14, and 1.08±0.13, which was significantly higher than that in group CT (with t values from 4.808 to 8.568, P values below 0.01). (3) Compared with those of volunteer in group HC, content of IL-2 in culture supernatant of T lymphocytes of patients in group CT was significantly decreased from PTD 1 to 7 (with t values from 8.073 to 9.288, P values below 0.01), content of IL-4 in serum of patients in group CT was significantly increased from PTD 1 to 7 (with t values from 18.926 to 41.451, P values below 0.01), and content of IFN-γ in serum of patients in group CT was significantly decreased from PTD 1 to 7 (with t values from 4.543 to 27.659, P values below 0.01). Compared with those in group CT, content of IL-2 in culture supernatant of T lymphocytes of patients in group UT was significantly increased from PTD 3 to 7 (with t values from 6.507 to 8.869, P values below 0.01), content of IL-4 in serum of patients in group UT was significantly decreased from PTD 3 to 7 (with t values from 6.922 to 8.843, P values below 0.01), and content of IFN-γ in serum of patients in group UT was significantly increased on PTD 5 and 7 (with t values respectively 5.369 and 13.521, P values below 0.01). (4) The percentages of CD14(+) monocytes with positive expression of HLA-DR of patients in group CT on PTD 1, 3, 5, and 7 were respectively (28±6)%, (25±7)%, (25±7)%, and (39±10)%, which were significantly lower than the percentage of volunteer in group HC [(87±8)%, with t values from 16.323 to 25.645, P values below 0.01]. The percentages of CD14(+) monocytes with positive expression of HLA-DR of patients in group UT on PTD 3, 5, and 7 were respectively (40±6)%, (42±9)%, and (49±10)%, which were significantly higher than those in group CT (with t values from 3.071 to 7.324, P values below 0.01).

CONCLUSIONSOn the basis of CT, additional ulinastatin intervention can decrease CD4(+) CD25(+) Tregs percentage, improve the immune function of T lymphocytes and T helper cells, and increase expression of HLA-DR on CD14(+) monocytes of patients with severe burn injury, thus improve the immune function of patients.

Burns ; drug therapy ; immunology ; Cells, Cultured ; Debridement ; Enzyme-Linked Immunosorbent Assay ; Glycoproteins ; therapeutic use ; Humans ; Interferon-gamma ; blood ; Interleukin-2 ; metabolism ; Interleukin-4 ; blood ; Monocytes ; immunology ; Skin Transplantation ; T-Lymphocytes, Regulatory ; immunology

OBJECTIVETo explore the change in the expression of extracellular heat shock protein 70 (eHSP70) and interleukin 2 (IL-2) and their correlation in intestine of rats with severe scald injury, and to observe the effects of eHSP70 on CD3(+) T lymphocytes in Peyer's patch of intestine in rats with severe scald injury in vitro.

METHODS(1) Sixty male SD rats were divided into normal control group (NC, n=10, only anesthetized) and scald group (S, n=50) according to the random number table. Rats in scald group were inflicted with 30% total body surface area full-thickness scald on the back. Ten rats from group NC immediately after anesthetization and 10 rats from group S at post injury hour (PIH) 3, 6, 12, 24, 48 were sacrificed to harvest their small intestines. The expressions of eHSP70 and IL-2 were determined with enzyme-linked immunosorbent assay (ELISA), and their correlation was analyzed. (2) Another 2 male SD rats were inflicted with the same injury as above. At PIH 12, CD3(+) T lymphocytes in Peyer's patch of small intestine were isolated and cultured with RPMI 1640 nutrient solution containing 10% fetal bovine serum. Cells were divided into blank control group (BC) and 5, 10, 20 μg/mL eHSP70 groups according to the random number table, with 6 wells in each group. Cells in group BC didn't receive any other treatment, while cells in the latter three groups were treated with corresponding mass concentration of recombinant rat eHSP70. After being cultured for 48 hours, the proportions of Th1 and Th2 in CD3(+) T lymphocytes, and the apoptosis rate of CD3(+) T lymphocytes were detected with flow cytometer, while the expressions of IL-2 and IL-10 in culture supernatant of cells were determined with ELISA. The cell experiments were repeated for 10 times. Data were processed with one-way analysis of variance, Kruskal-Wallis rank sum test, SNK-q test, and Pearson correlation analysis.

RESULTS(1) Compared with those in group NC [(1 278±135) and (48.6±4.9) ng/mg], the levels of eHSP70 [(728±93), (412±31), (314±21), (528±40), (1 028±97) ng/mg] and IL-2 [(38.6±2.3), (32.3±1.0), (25.3±3.6), (33.9±4.1), (44.3±2.6) ng/mg] in intestine of rats in group S obviously decreased at PIH 3, 6, 12, 24, 48 (with q values from 3.48 to 5.32, P values below 0.05), reaching the nadir both at PIH 12, with a significantly positive correlation between the level of IL-2 and the level of eHSP70 (r=0.920, P<0.01). (2) Compared with those in group BC [(8.6±1.1)% and (3.75±0.45)%], the proportion of Th1 obviously increased [(11.3±2.1)%, (15.7±1.8)%, (10.8±1.5)%, with q values from 2.97 to 4.57, P values below 0.05], while the proportion of Th2 obviously decreased [(2.39±0.38)%, (1.05±0.23)%, (2.67±0.26)%, with q values from 2.48 to 4.32, P values below 0.05] in CD3(+) T lymphocytes of rats in 5, 10, 20 μg/mL eHSP70 groups. Compared with those in group BC [(34.3±2.2)% and (254±16) pg/mL], the apoptosis rate of CD3(+) T lymphocytes obviously decreased [(26.1±2.6)%, (20.7±1.5)%, (31.5±2.4)%, with q values from 3.47 to 4.95, P values below 0.05], while the level of IL-2 obviously increased [(417±22), (587±19), (307±27) pg/mL, with q values from 3.02 to 4.98, P values below 0.05] in culture supernatant of CD3(+) T lymphocytes of rats in 5, 10, 20 μg/mL eHSP70 groups. There was no significant difference in the level of IL-10 in culture supernatant of CD3(+) T lymphocytes of rats among the four groups (F=2.12, P>0.05).

CONCLUSIONSThe expressions of eHSP70 and IL-2 in intestine of rats are decreased after severe scald, with a obviously positive correlation between them. eHSP70 can promote the differentiation of CD3(+) T lymphocytes in Th1 orientation, decrease the apoptosis rate of the cells, and promote the release of IL-2 of cells in Peyer's patch of intestine in rats with severe scald injury in vitro.

Animals ; Burns ; metabolism ; CD3 Complex ; metabolism ; Enzyme-Linked Immunosorbent Assay ; HSP70 Heat-Shock Proteins ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Intestine, Small ; metabolism ; Male ; Peyer's Patches ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Th1 Cells ; cytology