[Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns].

Objective: To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis. Methods: This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results: Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions: The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

[Visual analysis of the current research status and development of burn-related coagulation dysfunction].

Objective: To conduct a visual analysis of the literature on burn-related coagulation dysfunction and to explore the current research status, evolution process, hot topics, and future research trends in burn-related coagulation dysfunction at home and abroad. Methods: The bibliometrics method was used. The literature on burn-related coagulation dysfunction which were published in Web of Science and China National Knowledge Internet databases from January 1, 1950 to May 1, 2022, and met the inclusion criteria were retrieved for publication volume analysis. The literature on burn-related coagulation dysfunction were retrieved as above in the core collection of Web of Science and China National Knowledge Internet databases, and CiteSpace 5.8.R3 software was used to perform co-occurrence analysis, cluster analysis, and literature co-citation analysis of key words. Results: A total of 501 and 235 literature on burn-related coagulation dysfunction were retrieved from Web of Science database and China National Knowledge Internet database, respectively. The literature on burn-related coagulation dysfunction emerged from 1975 and 1950, respectively, in China and abroad, which were gradually increased later. The frequency and centrality of Chinese key words such as , , were high in 235 literature in China National Knowledge Internet database, and the frequency and centrality of key words such as burn, coagulation, and deep vein thrombosis were high in 340 literature in the core collection of Web of Science database. In China National Knowledge Internet database, the top 6 Chinese key words in terms of burst intensity were , , , , , , and the first 3 among which were burst key words in the early stage; and in the core collection of Web of Science database, the key words with higher burst intensity were disseminated intravascular coagulation and pulmonary embolism, which were the burst key words in the early stage. The representative clustering labels in China National Knowledge Internet database were #0 , #1 , and #2 , etc., and the representative clustering labels in the core collection of Web of Science database were #0 risk, #1 surgical patient, and #2 sepsis. Early researches in China National Knowledge Internet database and the core collection of Web of Science database focused on the presence of burn-related coagulation dysfunction itself, while the late researches focused on the relationship between burn-related coagulation dysfunction and inflammation, immunity, coagulation in general, and wounds. From 2010 onwards, there were a large number of core cited literature in the core collection of Web of Science database, and the prevention and treatment of vein thromboembolism was the most popular research direction in recent years. The researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction would be the main research directions in the future. Conclusions: The research hotspots and evolution processes of burn-related coagulation dysfunction at home and abroad have both similarities and differences, and the current research hotspot is the relationship between coagulation and inflammation, immunity. With researches increasingly deepening, the researches on optimization and standardization of diagnostic methods and the overall mechanism of burn-related coagulation dysfunction will be the main research directions in the future.

[Effects of non-muscle myosin â ¡ silenced bone marrow-derived mesenchymal stem cells transplantation on lung extracellular matrix in rats after endotoxin/lipopolysaccharide-induced acute lung injury].

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.

[Retrospective cohort study on the coagulation characteristics of adult patients with extensively severe burn in shock stage and its alarming value].

Objective: To study the coagulation characteristics of adult patients with extensively severe burn in shock stage and its alarming value. Methods: Retrospective cohort study was performed on medical records of 37 adult patients with extensively severe burn who were admitted to the First Affiliated Hospital of Naval Medical University from January 2014 to December 2019 and met the inclusion criteria. The patients were divided into survival group (n=23, 17 males and 6 females, aged 41 (31, 51) years) and death group (n=14, 11 males and 3 females, aged 50 (43, 58) years) according to the prognosis of within 60 d after burn. Basic data of patients in the two groups and their routine coagulation indexes during shock period including prothrombin time (PT), thrombin time, activated partial thromboplastin time (APTT), D-Dimer, fibrinogen degradation product (FDP), fibrinogen, platelet, and international normalized ratio (INR) were recorded. Data were statistically analyzed with Wilcoxon rank sum test and Fisher's exact probability test, prognosis-related factors was analyzed with single factor and multivariate logistic regression analysis (α selected=0.05, α excluded=0.1), and receiver operating characteristic (ROC) curve analysis were established to screen out the risk factors. All the patients were grouped into high score group and low score group according to the optimal threshold value, Kaplan-Meier method was used for survival analysis and Log-rank test was performed between the two groups. Results: Total burn surface area (TBSA) of patients in death group was obviously larger than that in survival group (Z=2.980, P<0.01), while there were no statistically significant difference in the other indexes between the two groups (P>0.05). Compared with those in survival group (16.10 (14.30, 16.90) s, 40.80 (36.20, 42.80) s, 1.30 (1.10, 1.40)), PT (18.70 (16.30, 22.70) s), APTT (46.45 (41.00, 57.10) s) and INR (1.55 (1.30, 1.96)) of patients in death group were significantly increased (Z=2.540, 2.330, 2.300, P<0.05), there were no statistically significant difference in the other indexes between the two groups (P>0.05). Single factor logistic regression analysis showed TBSA, PT, and APTT were factors related to death of adult patients with extensively severe burn within 60 d after burn (odds ratio (OR)=1.190, 1.214, 1.109, 95% confidence interval (CI)=1.053-1.346, 1.008-1.461, 1.012-1.215, P<0.05 or P<0.01). FDP and INR were potential factors related to death of adult patients with extensively severe burn within 60 d after burn (OR=1.040 and 4.559, 95% CI =0.998-1.083 and 0.918-22.641, P<0.1). Multivariate logistic stepwise regression was used to build models of APTT+ FDP+ TBSA and APTT+ FDP. Area under the curve (AUC) of APTT+ FDP+ TBSA model score was 0.944 (95% CI= 0.873-1.000), which was higher than AUC of APTT+ FDP model score (0.843, 95% CI=0.713-0.973) by ROC curve analysis. Optimal threshold value of APTT+ FDP+ TBSA model score was -0.879 4 with sensitivity of 100% (95% CI=100%-100%) and specificity of 87% (95% CI=74%-100%). Survival ratio of patients in high score group with optimal threshold value higher than -0.879 4 was significantly lower than that in low score group with optimal threshold value lower than -0.879 4, χ(2)=27.090, P<0.01. Conclusions: The coagulation state of adult patients with extensively severe burn in shock stage is characterized with procoagulant and hemostatic dysfunctions accompanied by enhanced fibrinolytic activity. The risk of death is significantly increased in adult patients with extensively severe burn with APTT+ FDP+ TBSA model score higher than -0.879 4.

Identification of microRNAs present in congenital heart disease associated copy number variants.

PURPOSE: Congenital heart disease (CHD) is the most common congenital anomaly in newborns and about 1.35 million infants are born with CHD each year worldwide. Recently a large category of copy number variants (CNVs), were established to be a major contributor of the pathophysiology of CHD. To date most studies focused on the analysis of CNV categories or the protein coding regions without investigation on the impact of non-coding regulatory microRNAs (miRNAs). MATERIALS AND METHODS: Here with an array comparative genome hybridisation data set and a gene expression profile data set, we investigated the contribution of miRNAs in CNVs towards the development of CHD. RESULTS: Approximately 18% of the identified high frequency CNV loci were shown to harbor miRNAs. According the expression profile analysis, 52 target genes of 16 miRNAs showed association with CHD. Targets of hsa-miR-650 was reported to be enriched with genes of cardiac dysfunctions and heart failure categories previously. In the constructed network, all 12 miRNAs directly or indirectly interacts with CHD related genes and hsa-miR-570 showed the highest degree. CONCLUSIONS: Our study highlights the significance of CNV-microRNAs and their target genes in the pathogenesis of CHD. This knowledge will facilitate the identification of miRNA biomarkers and the development of new therapeutics for CHD.