The systemic inflammation indexes after admission predict in-hospital mortality in patients with extensive burns.

PURPOSE: To explore the clinical value of various complete blood count (CBC)-derived inflammation indicators to predict in-hospital mortality in patients with extensive burns. METHODS: Systemic inflammation indexes, including lymphocyte-platelet ratio (LPR), neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), neutrophil-to-lymphocyte * platelet (NLPR), systemic inflammation index (SII), and systemic inflammation response index (SIRI) on days 1, 3, and 7 after admission were calculated in 135 patients with extensive burns. RESULTS: We included 135 patients with extensive burns, including 97 survivors and 38 non-survivors. After adjusting for confounders, only the LPR on day 1, NLPR on days 3 and 7 were significantly associated with survival (OR= 1.237, 1.097, 1.104; 95 % CI: 1.055-1.451, 1.002-1.202, 1.005-1.212; respectively) in the analysis of multivariate logistic regression. The optimum cutoff values of the LPR on day 1 and NLPR on day 3 were 6.37 and 8.06, and the area under the curves (AUC) were 0.695 and 0.794, respectively. The AUC of NLPR on day 7 had the highest value, 0.814, and the optimum cut-off value was 3.84. The efficacy of LPR on day 1, NLPR on days 3 and 7 combined with the burn prognostic score index in predicting the prognosis of patients was higher than that of the burn index alone, and the three composite inflammatory indexes combined with PBI had the highest efficacy in predicting the prognosis (AUC = 0.994). Kaplan-Meier survival analysis showed poor prognosis in patients with higher LPR on day 1 and higher NLPR on days 3 and 7 (log-rank χ2 =9.623,31.564, 20.771, respectively; P < 0.01). CONCLUSIONS: LPR on day 1 and NLPR on days 3 and 7 after admission are reliable predictors of prognosis in patients with severe extensive burns. The combination of the burn prognostic score index, LPR on day 1, and NLPR on days 3 and 7 was superior to the burn indexes alone in predicting a patient's prognosis.

Global research trends and prospects related to tumor microenvironment within Triple Negative Breast Cancer: a bibliometric analysis.

Background and aims: The tumor microenvironment (TME) has pivotal parts within multiple tumor models of onset/progression, such as triple-negative breast cancer (TNBC). This bibliometric analysis was developed to explore trends and research niches revolving around TME in TNBC. Methods: Web of Science Core Collection was queried for identifying studies linked with TME in TNBC, after which the VOSviewer, CiteSpace, and R software programs were used to conduct bibliometric analyses and to generate corresponding visualizations. Results: In total, this study included 1,604 studies published from 2005-2023. The USA and China exhibited the highest numbers of citations, and the research institutions with the greatest output in this field included Harvard University, the University of Texas System, and Fudan University. Ying Wang from Sun Yat-Sen University was the most published and most cited author in this space. The highest number of articles were published in Cancer, while the greatest co-citation number was evident in Breast Cancer Research. Important keywords related to this research topic included metastasis, tumor-infiltrating lymphocytes, immunotherapy, chemotherapy, and nanoparticles. In particular, pembrolizumab, immunotherapy, nanoparticles, combination treatment, and biomarkers were topics of marked interest in recent reports. Conclusion: The TME in TNBC is an area of rapidly growing and evolving research interest, with extensive global collaboration helping to drive this field forward. Antitumor therapies targeting the TME in TNBC patients represent an emerging topic of future research, providing opportunities for translational findings. The results of this analysis may provide additional guidance for work focused on the TME in TNBC.

Correlation Between MMP9 Promoter Methylation and Transient Ischemic Attack/Mild Ischemic Stroke with Early Cognitive Impairment.

Background/Objective: Dyskinesia caused by transient ischemic attack (TIA) and mild ischemic stroke (MIS) is mild and short-lived; however, cognitive impairment (CI) can occur in the acute phase and be easily overlooked. DNA methylation is an epigenetic phenomenon that can affect gene expression through gene silencing. Blood levels of matrix metalloproteinase (MMP) 9 are elevated in ischemic stroke patients and is associated with the destruction of the blood-brain barrier and the occurrence of CI. No studies have investigated the relationship between MMP9 gene methylation and TIA/MIS with early cognitive impairment (ECI). As such, the purpose of the present study was to investigate the correlation between MMP9 gene methylation and TIA/MIS with ECI. Methods: Data from 112 subjects were collected, including 84 with TIA/MIS (National Institutes of Health Stroke Scale <5 points) and 28 non-stroke control subjects. Patients were evaluated within 7 days of TIA/MIS onset according to four single-domain cognitive scales. Whole blood DNA methylation was detected using MethylTarget sequencing technology. Comparison of MMP9 gene methylation levels among subgroups was performed using statistical methods. Results: The site S33-79 in the TIA/MIS group was hypomethylated compared with the control group, and sites S33-25 and S33-30 in TIA/MIS with ECI was hypomethylated compared with TIA/MIS without ECI. Compared with the small artery occlusion group, MMP9 gene, S33-25, 30, 39, 53, 58, 73, 79, 113 and 131 sites in the large artery atherosclerosis group were hypomethylated. Conclusion: MMP9 gene hypomethylation sites were associated with TIA/MIS and TIA/MIS with ECI, and there was a strong correlation between MMP9 gene hypomethylation and atherosclerotic TIA/MIS. MMP9 gene methylation can reflect the severity of TIA/MIS. MMP9 gene hypomethylation sites may be used as potential biomarkers and therapeutic targets for TIA/MIS and TIA/MIS with ECI.

Physical exercise attenuates age-related muscle atrophy and exhibits anti-ageing effects via the adiponectin receptor 1 signalling.

BACKGROUND: Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet. METHODS: Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers. RESULTS: The C. elegans adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, P < 0.01), muscle weight (1.75-fold, P < 0.001), myonuclei number (1.33-fold, P < 0.05), muscle fibre CSA (1.39-fold, P < 0.05) and capillary abundance (2.19-fold, P < 0.001 for capillary density; 1.58-fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, P < 0.001) and mRNA levels (1.70-fold, P < 0.001) of p16INK4a , a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as 'AMPK signalling pathway' (P < 0.001), 'FOXO signalling pathway' (P < 0.001) and 'autophagy' (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, P < 0.001; 1.53-fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf-16, the FoxO homologue in C. elegans, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms. CONCLUSIONS: Our findings provide insights into how the AdipoR1 pathway has an impact on the anti-ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age-related loss of skeletal muscle.

Inflammatory response: The target for treating hyperpigmentation during the repair of a burn wound.

Hyperpigmentation is a common complication in patients with burn injuries during wound healing; however, the mechanisms underlying its occurrence and development remain unclear. Recently, postinflammatory hyperpigmentation (PIH) was found to result from overproduction of melanin. Local or systemic inflammatory responses are often observed in patients who develop hyperpigmentation. However, we lack studies on the relationship between PIH and burn injury. Therefore, we comprehensively reviewed the existing literature on the melanogenesis of the skin, inflammatory mechanisms in pigmentation, and local or systemic alteration in inflammatory cytokines in patients suffering from burn trauma to elucidate the relationship between PIH and burn injury. We believe that this review will guide further research on regulating melanin production in the burn management process.

Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Right-to-left shunt and subclinical ischemic brain lesions in Chinese migraineurs: a multicentre MRI study.

BACKGROUND: Migraine is considered as a risk factor for subclinical brain ischemic lesions, and right-to-left shunt (RLS) is more common among migraineurs. This cross-sectional study assessed the association of RLS with the increased prevalence of subclinical ischemic brain lesions in migraineurs. METHODS: We enrolled 334 migraineurs from a multicentre study from June 2015 to August 2016. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤ microbubbles (MBs) ≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. RESULTS: We found no significant differences between migraineurs with RLS and migraineurs without RLS in subclinical ischemic brain lesions.SBI and WMHs did not increase with the size of the RLS(p for trend for SBI = 0.066, p for trend for WMHs = 0.543). Furthermore, curtain RLS in migraineurs was a risk factor for the presence of SBI (p = 0.032, OR = 3.47; 95%CI: 1.12-10.76). There was no association between RLS and the presence of WMHs. CONCLUSION: Overall, RLS is not associated with increased SBI or WMHs in migraineurs. However, when RLS is present as a curtain pattern, it is likely to be a risk factor for SBIs in migraineurs. TRIAL REGISTRATION: No. NCT02425696 ; registered on April 21, 2015.

Influence of miR-155 on Cell Apoptosis in Rats with Ischemic Stroke: Role of the Ras Homolog Enriched in Brain (Rheb)/mTOR Pathway.

BACKGROUND We designed and carried out this study to examine the role of miR-155 and the Rheb/mTOR pathway in ischemic stroke. We also investigated how these two elements interact with each other and contribute to injuries resulting from ischemic stroke. MATERIAL AND METHODS We used both a middle cerebral artery occlusion rat model in vivo and an oxygen-glucose deprivation cell model in vitro to simulate the onset of ischemic stroke. miR-155 mimics, miR-155 inhibitors, and Rheb siRNA were transfected to alter the expression of miR-155 and Rheb. Infarct sizes were measured using magnetic resonance imaging (MRI) and triphenyltetrazolium chloride (TTC) staining; cell apoptosis rates were calculated using Annexin V-FITC/PI staining and flow cytometry. Levels of miR-155, Rheb, mTOR, and S6K were examined by RT-PCR, immunofluorescence, and western blot. We performed a luciferase activity assay so that the association between miR-155 and Rheb could be fully assessed. RESULTS We demonstrated that miR-155 bound the 3'-UTR of Rheb and suppressed Rheb expression. As suggested by animal models, significant cerebral infarct volumes and cell apoptosis were induced by increased expression of miR-155 and decreased expression of Rheb, mTOR, and p-S6K (P<0.05). miR-155 inhibitors exhibited protective effects on ischemic stroke, including down-regulation of infarction size in cerebral tissues in vivo and reduced apoptosis of BV2 cells in vitro with increased expression of Rheb, mTOR and p-S6K (P<0.05). These protective effects could be substantially antagonized by the transfection of Rheb siRNA (P<0.05). CONCLUSIONS Inhibition of miR-155 may play protective roles in ischemic stroke by phosphorylating S6K through the Rheb/mTOR pathway.

Biomechanics analysis for the treatment of ischemic necrosis of the femoral head by using an interior supporting system.

OBJECTIVE: This work aims to perform a biomechanical test to evaluate the effect of interior supporting system and tantalum rod in simulating the treatment of ischemic necrosis of the femoral head. METHOD: Three models were established: control group (group A), interior supporting system group (group B), and tantalum rod group (group C). Step-by-step loading was applied on the top of the femoral head until femoral head damage occurs by using the testing machine of the material test system. Strain and maximum load were applied until the femoral head collapses. The damage to the trochanteric fossa, femur calcar, and greater trochanter were compared. RESULTS: (1) The strain on the trochanteric fossa shows the following order: group C > group A and group B (P < 0.05). No significant difference was observed among groups for the other parts (P > 0.05). (2) The maximum load in group B is larger than that in groups A and C (P < 0.05). No significant difference in the maximum load was observed among the three groups when the femoral head was destroyed. CONCLUSIONS: The compression strain and bearing load of the femoral head are close to normal after placement of an interior supporting system and tantalum rod. The interior supporting system helps prevent femoral head collapse.

Carotid atherosclerosis in ischemic cerebrovascular patients.

BACKGROUND: Cerebral emboli resulting from atherosclerosis at the carotid bifurcation is a major cause of ischemic stroke. A convenient and prompt evaluation is necessary for secondary prevention and treatment. METHODS: In this study, one hundred and thirty eight patients with cerebral ischemic events were enrolled; 100 patients with nonischemic cerebral diseases were enrolled as controls. Noninvasive ultrasound was used to measure the atherosclerotic plaques and intima-media thickness (IMT) of carotid and femoral artery. RESULTS: Our results showed that patients in study group had higher incidence and severity of carotid and femoral plaques, and higher mean intima-media thickness (IMT) at both the carotid and femoral sites compared with that of controls (p < 0.01). Carotid atherosclerosis were highly prone to have instability plaques in study group(p < 0.001). CONCLUSIONS: This cross-sectional study showed that, the prevalence of carotid atherosclerosis and the unstable plaques were higher in cerebral ischemic patients. KEYWORDS: Carotid artery; Atherosclerosis; Intima-media thickness; Cerebral ischemic stroke.

Impaired Glucose Tolerance and Carotid Artery Atherosclerosis / 国际脑血管病杂志

Impaired glucose tolerance is the prediabetic state of diabetes mellitus,and its main manifestation is postprandial hyperglycemia.Studies in recent years have suggested that the large vascular disease of the impaired glucose tolerance state is similar to diabetes mellitus.The relationship between impaired glucose tolerance and atherosclerotic disease is increasingly receiving attention.This article reviews the relationship between both of them.

[Coronary resistance system in evaluation of microvascular dysfunction after intracoronary microembolization: an experimental study].

OBJECTIVE: To assess the microvascular function of coronary artery after intracoronary microembolization using coronary resistance system. METHODS: The left anterior descending coronary artery (LAD) of 10 pigs weighing 21 kg-25 kg were embolized by repetitive injection of microspheres 45 micro m in diameter through a 2.8F Tracker catheter. Intra-vascular ultrasound (IVUS) images, intracoronary Doppler and pressure signals in the middle segment of LAD were acquired by use of intracoronary ultrasound imaging catheter, Doppler flow wire and pressure wire separately. Intracoronary bolus injection of 18 micro g adenosine was administered to maximally vasodilate the coronary arterial bed through the 2.8F Tracker catheter. The resting and hyperemic signals were acquired respectively before microembolization and in different levels of microembolization. Coronary resistance system reflecting the resistance to pulsatile coronary flow was established by a self-made software of PC system. The resting and hyperemic CR parameters included average resting coronary resistance (rCR) and average minimal coronary resistance (min-CR), the first-harmonic rCR and min-CR, the first-harmonic rCR orientation and min-CR orientation, and so on. Factor analysis was performed to extract the best coronary parameter from the coronary resistance parameters. RESULTS: Factor analysis showed that the first-harmonic rCR and first-harmonic min-CR were correlated better with the first component extracted from the resting and hyperemic CR parameters than rCR and min-CR, with the correlation coefficient being 0.913 and 0.950 in the first-harmonic CR and first-harmonic min-CR respectively. No significant difference in min-CR was found between the value at the dosage of 5 x 10(4) microspheres and that before microembolization. The min-CR value increased markedly from 271 mm Hg.ml(-1).s(-1) +/- 99 mm Hg.ml(-1).s(-1) at the dosage of injecting 5 x 10(4) microspheres to 361 mm Hg.ml(-1).s(-1) +/- 158 mm Hg.ml(-1).s(-1) at the dosage of injecting 10 x 10(4) microspheres (P < 0.05). The min-CR value remained almost unchanged from the dosage of 10 x 10(4) to 15 x 10(4) microspheres. There was no significant difference concerning the first-harmonic min-CR between the value at the dosage of 5 x 10(4) microspheres and that before microembolization. Along with the increase of number of microspheres injected the min-CR value increased gradually. The min-CR value was increased significantly than that before microembolization since the number of microspheres injected surpassed 14 x 10(4). CONCLUSION: The first-harmonic min-CR reflected the coronary microvascular dysfunction in different extents of microembolization better than min-CR. The extent of coronary microvascular dysfunction wasn't linearly related to the extent of microembolization.

Neuroprotective effects of bone marrow stromal cells on rat organotypic hippocampal slice culture model of cerebral ischemia.

Organotypic hippocampal slice cultures prepared from newborn rats were maintained in vitro for 9 days. Cultures were then exposed to 30 min of combined oxygen-glucose deprivation (OGD). After OGD, the area covered by neurites was decreased. The dead cells of hippocampal slices in the ischemia group were 40.4% at day 3 and 41.6% at day 7 after OGD. The ultrastructure of the CA1 region of the slices was seriously damaged. While hippocampal slices were cultured in combination with bone marrow stromal cells (MSCs), the average area covered by neurites was comparatively increased. The dead cells were only 25.2% at day 3 and 27.1% at day 7 after coculture. The damage of the ultrastructure of the CA1 region in the coculture group was reduced significantly. Thus, in an in vitro model of simulated ischemia, MSCs can promote the outgrowth of neurites from hippocampal slices and alleviate cell damage. The neuroprotective effect might be mediated through diffusible neurotrophic factors secreted from MSCs.