[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.

[Comparison of machine learning method and logistic regression model in prediction of acute kidney injury in severely burned patients].

Objective: To build risk prediction models for acute kidney injury (AKI) in severely burned patients, and to compare the prediction performance of machine learning method and logistic regression model. Methods: The clinical data of 157 severely burned patients in August 2nd Kunshan factory aluminum dust explosion accident conforming to the inclusion criteria were collected. Patients suffering AKI within 90 days after admission were enrolled in group AKI, while the others were enrolled in non-AKI group. Single factor analysis was used to choose independent factors associated with AKI, including sex, age, admission time, features of basic injuries, initial score on admission, treatment condition, and mortality on post injury days 30, 60, and 90. Data were processed with Mann-Whitney U test, chi-square test, and Fisher's exact test. Variables with P<0.1 in single factor analysis and those with possible clinical significance were brought into the establishment of prediction model. Logistic regression and XGBoost machine learning algorithm were used to build the prediction model of AKI. The area under receiver operating characteristic curve (AUC) was calculated, and the sensitivity and specificity for optimal threshold value were also calculated for each model. Nonparametric resampling test was used to compare the significance of difference of AUC of the two models. Results: (1) Eighty-nine (56.7%) patients developed AKI within 90 days from admission. Compared with 68 patients in non-AKI group, 89 patients in group AKI were older (Z=-2.203, P<0.05), with larger total burn area and full-thickness burn area (Z=-5.200, -6.297, P<0.01), worse acute physical and chronic health evaluation (APACHE) Ⅱ score, abbreviated burn severity index score, and sequential organ failure assessment (SOFA) score on admission (Z=-7.485, -4.739, -4.590, P<0.01), higher occurrence rate of sepsis (χ(2)=33.087, P<0.01), higher rates of accepting tracheotomy, mechanical ventilation, and continuous renal replacement therapy (χ(2)=12.373, 17.201, 43.763, P<0.01), larger first excision area (Z=-2.191, P<0.05), and higher mortality on post injury days 30, 60, and 90 (χ(2)=7.483, 37.259, 45.533, P<0.01). There were no statistically significant differences in sex, open decompression, admission time, 24-hour fluid volume after admission, 48-hour fluid volume after admission, the first 24-hour urine volume, the second 24 hour urine volume, the first excision time, and inhalation injury (χ(2)=0.529, 3.318, Z=-1.746, -0.016, -1.199, -1.824, -0.625, -1.747, P>0.05). The rates of deep vein catheterization of patients in the two groups were both 100%. (2) There were twenty possible prediction variables for preliminary establishment of model according to the difference results of single factor analysis and clinical significance of variables. (3) The logistic regression prediction model had three variables: APACHE Ⅱ score [odds ratio (OR)=1.36, 95% confidence interval (CI)=1.20-1.53, P<0.001], sepsis (OR=2.63, 95% CI=0.90-7.66, P>0.05), and the first 24-hour urine volume (OR=0.71, 95% CI=0.50-1.01, P>0.05). The AUC of the logistic regression prediction model was 0.875 (95% CI=0.821-0.930), with the specificity and sensitivity of optimal threshold value 84.4% and 77.7%, respectively. (4) XGBoost machine learning model had seven main predictive variables: APACHE Ⅱ score, full-thickness burn area, 24-hour fluid volume after admission, sepsis, the first 24-hour urine volume, SOFA score, and 48-hour fluid volume after admission. The AUC of machine learning model was 0.920 (95% CI=0.879-0.962), higher than that of logistic regression model (P<0.001), with the specificity and sensitivity of optimal threshold value 89.7% and 82.0%, respectively. Conclusions: Sepsis and fluid resuscitation are two important predictive variables that can be intervened for AKI in severely burned patients. Machine learning method has a better performance and can provide more accurate prediction for individuals than logistic regression prediction model, and therefore has good clinical application prospect.

Expressions of survivin, P16(INK4a), COX-2, and Ki-67 in cervical cancer progression reveal the potential clinical application.

PURPOSE OF INVESTIGATION: To explore the significance of survivin, P16(INK4a), COX-2, and Ki-67 expressions for prediction of cervical cancer progression. MATERIALS AND METHODS: A retrospective study was performed in 129 cases including 24 squamous carcinoma of the cervix (SCC), 70 cervical intraepithelial neoplasias (CIN), 15 cervical condyloma acuminatum (CCA), ten chronic cervicitis (CC), and ten normal cervix (NC). Protein expressions were evaluated using immunohistochemistry. RESULTS: Survivin, P16(INK4a); COX-2, and Ki-67 were highly expressed in SCC and CIN compared with others. Their expression rates were gradually increased in CIN I, CIN II, CIN III, and SCC groups, showing 72.00%, 88.00%, 90.00%, and 95.83% for P16(INK4a), 68.00%, 84.00%, 95.00% and 100.00% for COX-2, 76.00%, 96.00%, 100.00%, and 100.00 for Ki-67, respectively. There were significant correlations between survivin and P16(INK4a), COX-2, Ki-67, as well as P16(INK4a) and Ki-67. CONCLUSION: Survivin, P16(INK4a), COX-2 and Ki-67 play critical roles for development and progression of cervical cancer.

Dexamethasone inhibits the effect of paclitaxel on human ovarian carcinoma xenografts in nude mice.

BACKGROUND: Recent studies showed that dexamethasone (DEX) could render cancer cells resistant to paclitaxel (PTX) induced apoptosis though an unknown mechanism. AIM: This study aimed to evaluate the influence of DEX pretreatment on the anti-tumor effect of PTX in an in vivo xenograft model with grafted ovarian cancer SKOV-3 cells innude mice. MATERIALS AND METHODS: The xenograft procedure was performed, and the nude mice were grouped into four cohorts of ten that received the following treatments: Control group, DEX group, PTX group and DEX+PTX group. Individual treatments were administered once every three days for a total of 6 courses. The growth of tumors and the inhibition rates were measured. Changes in tissue morphology and cellular ultrastructure were observed using light and transmission electron microscopy. Immunohistochemistry was performed to examine the expression of Ki-67, Bcl-xL and cleaved caspase-3. RESULTS: Premedication with DEX reduced the inhibitory effect of PTX on tumor growth by approximately 20% compared to the PTX-only-treated group in the ovarian carcinoma xeno-grafted mice. Hematoxylin-eosin (H&E) staining revealed that significantly fewer cells exhibited vacuolization and apoptosis in the DEX + PTX group compared to the PTX group. Apoptotic characteristics including karyopyknosis, nuclear chromatin condensation along the nuclear membrane and aggregation were observed in both DEX+PTX and PTX groups under electron microscopy. However, these characteristics were less significant in the DEX+PTX group than those in the PTX group. The immunohistochemistry demonstrated that protein expression levels of Ki-67 and Bcl-xL were significantly increased, whereas cleaved caspase-3 decreased in the DEX+PTX group, compared to PTX group (p < 0.0125). CONCLUSIONS: DEX inhibits the therapeutic efficacy of PTX in a human ovarian carcinoma SKOV-3 xenograft model.

Contrast-enhanced ultrasound for the diagnosis of hepatic adenoma.

Nine hepatic adenomas (HA) diagnosed by contrast-enhanced ultrasound (CEUS) among 123 liver lesions (89 patients) were evaluated retrospectively; five were confirmed through pathological diagnosis. Time-intensity curves (TIC), contrast medium arriving time (AT), peak time (PT) and retrogression time (RT) for HA were compared with 30 hepatocellular carcinomas (HCC) and six focal nodular hyperplasias (FNH). Significant differences existed between HA and poorly-differentiated HCC in AT, PT and RT, and between HA and well-differentiated HCC in AT. Differential diagnosis between HA and FNH was determined only through their different perfusion and arterial morphological features: HA showed typical perfusion characteristic of 'fast-in, slow-out', with a centripetal or mixed-filling pattern in the arterial phase, while FNH showed a centrifugal filling pattern. In conclusion, CEUS was helpful for identifying HA but it may be relatively difficult to distinguish between HA and some well-differentiated HCC or FNH.