A 10-year mono-center study on patients with burns ≥70% TBSA: prediction model construction and multi-center validation: retrospective cohort.

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

A multi-center cross-sectional study on identification of influencing factors of medical students' emotional engagement in China.

BACKGROUND: Studies exploring influencing factors of emotional engagement among medical students are scarce. Thus, we aimed to identify influencing factors of medical students' emotional engagement. METHODS: We carried out a multi-center cross-sectional study among 10,901 medical students from 11 universities in China. The Chinese version of Utrecht Work Engagement Scale-Student version (UWES-S) was used to evaluate emotional engagement level of medical students. The predictors related to engagement level were determined by the logistic regression analysis. Furthermore, we constructed a nomogram to predict emotional engagement level of medical students. RESULTS: A total of 10,576 sample were included in this study. The mean emotional engagement score was 74.61(± 16.21). In the multivariate logistic regression model, we found that males showed higher engagement level compared with females [odds ratio (OR) (95% confidence interval (CI)): 1.263 (1.147, 1.392), P < 0.001]. Medical students from the second batches of medical universities had higher engagement level and from "Project 985" universities had lower engagement level compared with 211 project universities [OR (95%CI): 1.376 (1.093, 1.733), P = 0.007; OR (95%CI): 0.682 (0.535, 0.868), P = 0.002]. Medical students in grade 4 and grade 2 presented lower engagement level compared with in grade 1 [OR (95%CI): 0.860 (0.752, 0.983), P = 0.027; OR (95%CI): 0.861 (0.757, 0.980), P = 0.023]. Medical students lived in provincial capital cities had higher engagement level compared with in country [OR (95%CI): 1.176 (1.022, 1.354), P = 0.024]. Compared with eight-year emotional duration, medical students in other emotional duration (three-year and four-year) had lower engagement level [OR (95%CI): 0.762 (0.628, 0.924), P = 0.006]. Medical students' engagement level increased with increases of grade point average and interest in studying medicine. Medical students learned by converging style showed lower engagement level [OR (95%CI): 0.827 (0.722, 0.946), P = 0.006] compared with accommodating style. The model showed good discriminative ability (area under curve = 0.778), calibrating ability and clinical utility. CONCLUSIONS: We identified influencing factors of medical students' emotional engagement and developed a nomogram to predict medical students' emotional engagement level, providing reference and convenience for educators to assess and improve emotional engagement level of medical students. It is crucial for educators to pay more attention to emotional engagement of medical students and adopt effective strategies to improve their engagement level.

Tracing the evolving dynamics and research hotspots of microbiota and immune microenvironment from the past to the new era.

Gut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like the inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. This article aims to review the documents in this field and summarize the research hotspots as well as developing processes. Gut microbiota and immune microenvironment-related documents from 1976 to 2022 were obtained from the Web of Science Core Collection database. Bibliometrics was used to assess the core authors and journals, most contributive countries and affiliations together with hotspots in this field and keyword co-occurrence analysis. Data were visualized to help comprehension. Nine hundred and twelve documents about gut microbiota and immune microenvironment were retrieved, and the annual publications increased gradually. The most productive author, country, and affiliation were "Zitvogel L," USA and "UNIV TEXAS MD ANDERSON CANC CTR," respectively. FRONTIERS IN IMMUNOLOGY, CANCERS, and INTERNATIONAL JOURNAL OF MOLECULAR SCIENCE were the periodicals with most publications. Keyword co-occurrence analysis identified three clusters, including gut microbiota, inflammation, and IBD. Combined with the visualized analysis of documents and keyword co-occurrence as well as literature reading, we recognized three key topics of gut microbiota: cancer and therapy; immunity, inflammation and IBD; acute injuries and metabolic diseases. This article revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.IMPORTANCEGut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. While the application of bibliometrics in the field of gut microbiota and immune microenvironment still remains blank, which focused more on the regulation of the gut microbiota on the immune microenvironment of different kinds of diseases. Here, we intended to review and summarize the presented documents in gut microbiota and immune microenvironment field by bibliometrics. And we revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.

Mapping intellectual structure and research hotspots in the field of fibroblast-associated DFUs: a bibliometric analysis.

Background: Diabetic foot ulcers (DFUs) are one of the most popular and severe complications of diabetes. The persistent non-healing of DFUs may eventually contribute to severe complications such as amputation, which presents patients with significant physical and psychological challenges. Fibroblasts are critical cells in wound healing and perform essential roles in all phases of wound healing. In diabetic foot patients, the disruption of fibroblast function exacerbates the non-healing of the wound. This study aimed to summarize the hotspots and evaluate the global research trends on fibroblast-related DFUs through bibliometric analysis. Methods: Scientific publications on the study of fibroblast-related DFUs from January 1, 2000 to April 27, 2022 were retrieved from the Web of Science Core Collection (WoSCC). Biblioshiny software was primarily performed for the visual analysis of the literature, CiteSpace software and VOSviewer software were used to validate the results. Results: A total of 479 articles on fibroblast-related DFUs were retrieved. The most published countries, institutions, journals, and authors in this field were the USA, The Chinese University of Hong Kong, Wound Repair and Regeneration, and Seung-Kyu Han. In addition, keyword co-occurrence networks, historical direct citation networks, thematic map, and the trend topics map summarize the research hotspots and trends in this field. Conclusion: Current studies indicated that research on fibroblast-related DFUs is attracting increasing concern and have clinical implications. The cellular and molecular mechanisms of the DFU pathophysiological process, the molecular mechanisms and therapeutic targets associated with DFUs angiogenesis, and the measures to promote DFUs wound healing are three worthy research hotspots in this field.

Pan-cancer analysis reveals signal transducer and activator of transcription (STAT) gene family as biomarkers for prognostic prediction and therapeutic guidance.

Background: The signal transducer and activator of transcription (STAT) gene family have been widely found to regulate cell proliferation, differentiation, apoptosis, and angiogenesis through complex signaling pathways, and thus impacting tumor formation and development in different types of tumor. However, the roles of STATs on prognostic prediction and therapeutic guidance in pan-cancer remain unexplored. Materials and Methods: The dataset of 33 types of TCGA tumor, para-carcinoma and normal tissues, was obtained from the UCSC Xena database, including the gene expression profiles in the formats of FPKM value, demographic characteristics, clinical information, and survival data of STATs. Differential expression and co-expression analyses, WGCNA, clinical relevance analysis, immune subtype analysis, tumor stemness analysis, tumor purity analysis, immune infiltration analysis, immunotherapy related analysis, tumor mutation related analysis, and drug sensitivity analysis were performed by R software. Results: Differential expression of STAT1 was found between normal and BRCA tissues (p < 0.001, log2FC = 0.895). Additionally, the strongest correlation among STATs lied between STAT1 and STAT2 (correlation coefficient = 0.6). Moreover, high expression levels of STAT1 (p = 0.031) were revealed to be notably correlated with poor prognosis in KIRP. In addition, STAT1 expressed the highest value in immune subtypes C1, C2, C3, and C6 in LUAD. What's more, strong negative correlations were demonstrated between expression of STAT6 and mDNAss and mRNAss of TGCT. Additionally, STAT4 expression was characterized to be significantly negatively correlated with tumor purity of the majority of cancer types. Moreover, STAT1 and STAT3 were shown to be generally high-expressed in pan-cancer myeloid cells, and STATs all had positive correlation with the infiltration of the majority of immune cells. In addition, STATs were revealed to be closely linked with immunotherapy response. What's more, STAT4 expression was identified to have a strong negative correlation with TMB value in DLBC. Last but not least, positive correlations were accessed between STAT5 and sensitivity of Nelarabine (cor = 0.600, p < 0.001). Conclusion: In the present study, we identified STATs as biomarkers for prognostic prediction and therapeutic guidance in pan-cancer. Hopefully our findings could provide a valuable reference for future STATs research and clinical applications.

Decoupled Control of Grasp and Rotation Constraints During Prehension of Weightless Objects.

Gravity provides critical information for the adjustment of body movement or manipulation of the handheld object. Indeed, the changes in gravity modify the mechanical constraints of prehensile actions, which may be accompanied by the changes in control strategies. The current study examined the effect of the gravitational force of a handheld object on the control strategies for subactions of multidigit prehension. A total of eight subjects performed prehensile tasks while grasping and lifting the handle by about 250 mm along the vertical direction. The experiment consisted of two conditions: lifting gravity-induced (1g) and weightless (0g) handheld objects. The weightless object condition was implemented utilizing a robot arm that produced a constant antigravitational force of the handle. The current analysis was limited to the two-dimensional grasping plane, and the notion of the virtual finger was employed to formulate the cause-effect chain of elemental variables during the prehensile action. The results of correlation analyses confirmed that decoupled organization of two subsets of mechanical variables was observed in both 1g and 0g conditions. While lifting the handle, the two subsets of variables were assumed to contribute to the grasping and rotational equilibrium, respectively. Notably, the normal forces of the thumb and virtual finger had strong positive correlations. In contrast, the normal forces had no significant relationship with the variables as to the moment of force. We conclude that the gravitational force had no detrimental effect on adjustments of the mechanical variables for the rotational action and its decoupling from the grasping equilibrium.

Effects of intestinal microbes on rheumatic diseases: A bibliometric analysis.

Background: Rheumatic diseases (RD) are a group of multi-system inflammatory autoimmune diseases whose causes are still under study. In the past few decades, researchers have found traces of the association between rheumatic diseases and intestinal microbiota, which can partially explain the pathogenesis of rheumatic diseases. We aimed to describe the research trend and main divisions on how gut flora interreacts with rheumatic diseases, and discussed about the possible clinical applications. Methods: We analyzed bibliometric data from the Web of Science core collection (dated 15th May 2022). Biblioshiny R language software packages (bibliometrix) were used to obtain the annual publication and citations, core sources according to Bradford's law, and country collaboration map. We designed and verified the keyword co-occurrence network and strategic diagram with the help of VOSviewer and CiteSpace, subdivided the research topic into several themes and identified research dimensions. The tables of most local cited documents and core sources were processed manually. Furthermore, the Altmetric Attention Score and the annual Altmetric Top 100 were applied to analyze the annual publication and citation. Results: From a total of 541 documents, we found that the overall trend of annual publication and citation is increasing. The major research method is to compare the intestinal microbial composition of patients with certain rheumatic disease and that of the control group to determine microbial alterations related to the disease's occurrence and development. According to Bradford's law, the core sources are Arthritis and Rheumatology, Annals of the Rheumatic Diseases, Current Opinion in Rheumatology, Nutrients, Rheumatology, and Journal of Rheumatology. Since 1976, 101 countries or regions have participated in studies of rheumatology and intestinal microbes. The United States ranks at the top and has the broadest academic association with other countries. Five themes were identified, including the pivotal role of inflammation caused by intestinal bacteria in the rheumatic pathogenesis, the close relationship between rheumatic diseases and inflammatory bowel disease, immunoregulation mechanism as a mediator of the interaction between rheumatic diseases and gut flora, dysbiosis and decreased diversity in intestine of patients with rheumatic diseases, and the influence of oral flora on rheumatic diseases. Additionally, four research dimensions were identified, including pathology, treatment, disease, and experiments. Conclusion: Studies on rheumatic diseases and the intestinal microbiota are growing. Attention should be paid to the mechanism of their interaction, such as the microbe-immune-RD crosstalk. Hopefully, the research achievements can be applied to diseases' prevention, diagnosis, and treatment, and our work can contribute to the readers' future research.

Frequency-Dependent Effects on Coordination and Prefrontal Hemodynamics During Finger Force Production Tasks.

Behavioral stability partially depends on the variability of net outcomes by means of the co-varied adjustment of individual elements such as multi-finger forces. The properties of cyclic actions affect stability and variability of the performance as well as the activation of the prefrontal cortex that is an origin of subcortical structure for the coordinative actions. Little research has been done on the issue of the relationship between stability and neuronal response. The purpose of the study was to investigate the changes in the neural response, particularly at the prefrontal cortex, to the frequencies of isometric cyclic finger force production. The main experimental task was to produce finger forces while matching the produced force to sine-wave templates as accurately as possible. Also, the hemodynamics responses of the prefrontal cortex, including oxy-hemoglobin concentration (ΔHbO) and the functional connectivity, were measured using functional near-infrared spectroscopy. The frequency conditions comprised 0.1, 1, and 2 Hz. The uncontrolled manifold (UCM) approach was applied to compute synergy indices in time-series. The relative phase (RP), the coefficient of variation (CV) of the peak and trough force values were computed as the indices of performance accuracy. The statistical parametric mapping (SPM) was implemented to compare the synergy indices of three frequency conditions in time-series. A less accurate performance in the high-frequency condition was caused not by the RP, but mainly by the inconsistent peak force values (CV; p < 0.01, η p 2 = 0.90). The SPM analysis revealed that the synergy indices were larger in the low-frequency than in high-frequency conditions. Further, the ΔHbO remained unchanged under all frequency conditions, while the functional connectivity decreased with an increase in the frequency of cyclic force production. The current results suggested that the concurrent activation of the prefrontal region mainly depends on the frequency of cyclic force production, which was associated with the strength of stability indices and performance errors. The current study is the first work to uncover the effect of frequency on the multi-finger synergies as to the hemodynamic response in the prefrontal cortex, which possibly provides a clue of the neural mechanism of synergy formation and its changes.

Elevated serum procalcitonin early after extensive burn: influencing factors and clinical significance.

The study was carried out to analyze the factors influencing the elevated serum procalcitonin (PCT) levels during the early phase of extensive burn, and to investigate its potential for sepsis prediction and prognosis. Clinical data of 324 patients with extensive burns treated at our department from July 2014 to December 2019 were retrospectively analyzed. Approximately half of the patients (50.93%) exhibited elevated serum PCT concentrations during the early phase, and elevated PCT levels may not be caused by infections. Early-phase PCT level was an independent risk factor for sepsis occurrence in extensive-burn patients within 60 days of injury. Burn index, degree of inhalation injury, and APACHE-II score influenced PCT level elevation during the early phase. Patient age, burn index, APACHE-II score at admission, early-phase PCT level, and sepsis occurrence were risk factors for mortality in extensive-burn patients. During the early phase, approximately 50.93% of the extensive-burn patients exhibited elevated PCT levels, which were associated with non-infectious factors. As elevated PCT level during the early phase predicted sepsis occurrence within 60 days of injury and was significantly associated with patient mortality, it might be a potential burn severity indicator during the early phase of burn injury.

MicroRNA-139-5p Promotes Functional Recovery and Reduces Pain Hypersensitivity in Mice with Spinal Cord Injury by Targeting Mammalian Sterile 20-like Kinase 1.

Currently, there is no cure for spinal cord injury (SCI), a heavy burden on patients physiology and psychology. We found that microRNA-139-5p (miR-139-5p) expression was significantly downregulated in damaged spinal cords in mice. So, we aimed to test the effect of treatment with miR-139-5p on functional recovery and neuropathic pain in mice with SCI and investigate the underlying mechanism. The luciferase reporter assay revealed that miR-139-5p directly targeted mammalian sterile 20-like kinase 1 (Mst1), and miR-139-5p treatment suppressed Mst1 protein expression in damaged spinal cords of mice. Wild-type mice and Mst1(-/-) mice were exposed to SCI and treated with miR-139-5p agomir via intrathecal infusion. Treatment of SCI mice with miR-139-5p accelerated locomotor functional recovery, reduced hypersensitivities to mechanical and thermal stimulations, and promoted neuronal survival in damaged spinal cords. Treatment with miR-139-5p enhanced phosphorylation of adenosine monophosphate-activated protein kinase alpha (AMPKα), improved mitochondrial function, and suppressed NF-κB-related inflammation in damaged spinal cords. Deficiency of Mst1 had similar benefits in mice with SCI. Furthermore, miR-139-5p treatment did not provide further protection in Mst1(-/-) mice against SCI. In conclusion, miR-139-5p treatment enhanced functional recovery and reduced pain hypersensitivity in mice with SCI, possibly through targeting Mst1.

HIPK2 sustains inflammatory cytokine production by promoting endoplasmic reticulum stress in macrophages.

Uncontrolled inflammatory cytokine production by macrophages contributes to numerous conditions, including infection, endotoxemia and sepsis. A previous study proposed that endoplasmic reticulum (ER) stress acts as an essential process in inflammatory cytokine production by macrophages. The present study used a mouse sepsis model and in vitro macrophages to demonstrate that homeodomain-interacting protein kinase 2 (HIPK2) sustained cytokine production in an ER stress-dependent manner. HIPK2 expression was upregulated in the early phase of lipopolysaccharide stimulation. HIPK2 knockdown attenuated IL-6 and TNF-α production, and p65 phosphorylation in macrophages. Furthermore, the attenuated cytokine production was abolished by the ER stress agonist tunicamycin. The activation of ER stress increased the levels of IL-6 and TNF-α, and the phosphorylation of p65, in macrophages following knockdown of HIPK2. Furthermore, HIPK2 inhibition attenuated the production of IL-6 and TNF-α in vitro and in vivo. Therefore, HIPK2 sustained inflammatory cytokine production by promoting ER stress in macrophages. Targeting HIPK2 may be a potential strategy for the management of uncontrolled inflammation in clinical settings.

Management of combined massive burn and blast injury: A 20-year experience.

INTRODUCTION: Blast injuries are complex types of physical trauma resulting from direct or indirect exposure to an explosion, which can be divided into four classes: primary, secondary, tertiary, and quaternary. Primary blast injury results in damage, principally, in gas-containing organs such as the lungs (blast lung injury, BLI). BLI is defined as radiological and clinical evidence of acute lung injury occurring within 12h of exposure to an explosion and not due to secondary or tertiary injury. BLI often combines with cutaneous thermal injury, a type of quaternary blast injury, either in terrorist bomb attacks or in civilian accidental explosions. This report summarizes our experience in the management of combined massive burn and BLI at a Shanghai Burn Center in China. METHODS: A retrospective observational analysis of clinical data was performed for massive burn patients with or without BLI during a 20-year interval. Patient characteristics, causes of injury, clinical parameters, management, and outcomes were recorded and evaluated. RESULTS: A total of 151 patients (120 males and 31 females) with severe burn injury (≥50% TBSA) treated at the Burn Center of Changhai Hospital in Shanghai between July 1997 and June 2017 were enrolled in this study. Their mean age was 38.6±17.8 (3-75) years. Among them, 28 patients had combined BLI and burn injury and 39 patients had no BLI or smoke inhalation injury (non-BLI-SII). No significant difference was observed in the burn area or full-thickness burn area between the two groups. The lowest PaO2/fraction of inspired oxygen (FiO2) ratio during the first 24h in BLI patients was significantly lower than that in non-BLI-SII patients. Exudative changes were observed by X-ray radiography in all BLI patients but not in non-BLI-SII patients within 6h after injury. A significantly higher proportion of colloids were used for fluid resuscitation in BLI patients than that in non-BLI-SII patients. A higher proportion and longer time of mechanical ventilation were needed for BLI patients than those for non-BLI-SII patients, and a higher proportion of patients received sedative agents in the BLI group than those in the non-BLI-SII group. The first escharectomy was performed relatively later in BLI patients than in non-BLI-SII patients because of more time taken by BLI patients to recover from lung injury. The length of ICU and hospital stay in BLI patients was significantly longer than that in non-BLI-SII patients. No significant difference in the overall mortality was detected between these two groups. CONCLUSION: It is a formidable challenge for clinicians to diagnose and manage massive burn patients combined with BLI. A comprehensive treatment approach is strongly recommended, including fluid resuscitation, airway management, mechanical ventilation, and surgical treatment. Given the high mortality of massive burn patients combined with BLI even in a recognized burn center, more prospective studies are encouraged to assess more effective strategies for the treatment of such patients.

Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis.

BACKGROUND: Less apoptosis and excessive growth of fibroblasts contribute to the progression of hypertrophic scar formation. Cuprous oxide nanoparticles (CONPs) could have not only inhibited tumor by inducing apoptosis and inhibiting proliferation of tumor cells, but also promoted wound healing. The objective of this study was to further explore the therapeutic effects of CONPs on hypertrophic scar formation in vivo and in vitro. METHODS: In vivo, a rabbit ear scar model was established on New Zealand albino rabbits. Six full-thickness and circular wounds (10 mm diameter) were made to each ear. Following complete re-epithelization observed on postoperative day 14, an intralesional injection of CONPs or 5% glucose solution was conducted to the wounds. The photo and ultrasonography of each wound were taken every week and scars were harvested on day 35 for further histomorphometric analysis. In vitro, the role of CONPs in human hypertrophic scar fibroblasts (HSFs) apoptosis and proliferation were evaluated by Tunnel assay, Annexin V/PI staining, cell cycle analysis, and EdU proliferation assay. The endocytosis of CONPs by fibroblasts were detected through transmission electron microscopy (TEM) and the mitochondrial membrane potential and ROS production were also detected. RESULTS: In vivo, intralesional injections of CONPs could significantly improve the scar appearance and collagen arrangement, and decreased scar elevation index (SEI). In vitro, CONPs could prominently inhibit proliferation and induce apoptosis in HSFs in a concentration-dependent manner. In addition, CONPs could be endocytosed into mitochondria，damage the mitochondrial membrane potential and increase ROS production. CONCLUSION: CONPs possessed the therapeutic potential in the treatment of hypertrophic scar by inhibiting HSFs proliferation and inducing HSFs apoptosis.

Effect of Kinetic Degrees of Freedom on Multi-Finger Synergies and Task Performance during Force Production and Release Tasks.

Complex structures present in a human body has relatively large degrees-of-freedom (DOFs) as compared to the requirement of a particular task. This phenomenon called motor redundancy initially deemed as a computational problem rather can be understood as having the flexibility to perform the certain task successfully. Hence, the purpose of our study was to examine the positive impact of extra DOFs (redundant DOFs) during force production tasks. For this purpose, an experimental setup was designed to simulate archery-like shooting, and purposeful organization of a redundant set of finger forces determined the stability of important performance variables as well as accurate and precise performance. DOFs were adjusted by changing the number of fingers explicitly involved in the task. The concept of motor synergy and computational framework of uncontrolled manifold (UCM) approach was used to quantify stability indices during finger force production. As a result, accuracy and precision of the task improved with an increase in DOFs. Also, the stability indices of net finger forces and moment increased with active DOFs of fingers. We concluded that the controller actively utilizes extra DOFs to increase the stability of the performance, which is associated with the improved accuracy and precision of the task.

Multi-Finger Interaction and Synergies in Finger Flexion and Extension Force Production.

The aim of this study was to discover finger interaction indices during single-finger ramp tasks and multi-finger coordination during a steady state force production in two directions, flexion, and extension. Furthermore, the indices of anticipatory adjustment of elemental variables (i.e., finger forces) prior to a quick pulse force production were quantified. It is currently unknown whether the organization and anticipatory modulation of stability properties are affected by force directions and strengths of in multi-finger actions. We expected to observe a smaller finger independency and larger indices of multi-finger coordination during extension than during flexion due to both neural and peripheral differences between the finger flexion and extension actions. We also examined the indices of the anticipatory adjustment between different force direction conditions. The anticipatory adjustment could be a neural process, which may be affected by the properties of the muscles and by the direction of the motions. The maximal voluntary contraction (MVC) force was larger for flexion than for extension, which confirmed the fact that the strength of finger flexor muscles (e.g., flexor digitorum profundus) was larger than that of finger extensor (e.g., extensor digitorum). The analysis within the uncontrolled manifold (UCM) hypothesis was used to quantify the motor synergy of elemental variables by decomposing two sources of variances across repetitive trials, which identifies the variances in the uncontrolled manifold (VUCM) and that are orthogonal to the UCM (VORT). The presence of motor synergy and its strength were quantified by the relative amount of VUCM and VORT. The strength of motor synergies at the steady state was larger in the extension condition, which suggests that the stability property (i.e., multi-finger synergies) may be a direction specific quantity. However, the results for the existence of anticipatory adjustment; however, no difference between the directional conditions suggests that feed-forward synergy adjustment (changes in the stability property) may be at least independent of the magnitude of the task-specific apparent performance variables and its direction (e.g., flexion and extension forces).

Deletion of mammalian sterile 20-like kinase 1 attenuates neuronal loss and improves locomotor function in a mouse model of spinal cord trauma.

Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score. Deletion of Mst1 in mice attenuated loss of motor neurons and suppressed microglial and glial activation following SCI. Deletion of Mst1 in mice reduced apoptosis via suppressing cytochrome c release and caspase-3 activation following SCI. Deletion of Mst1 attenuated mitochondrial dysfunction and increased ATP formation following SCI. Deletion of Mst1 in mice inhibited local inflammation following SCI, evidenced by reduced activities of myeloperoxidase and protein levels of TNF-α, IL-1ß, and IL-6. In conclusion, the present study demonstrated that deletion of Mst1 attenuated neuronal loss and improved locomotor function in a mouse model of SCI, via preserving mitochondrial function, attenuating mitochondria-mediated apoptotic pathway, and suppressing inflammation, at least in part.

[The myeloid cell leukemia-1 mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines].

OBJECTIVE: To investigate the regulatory mechanism of myeloid cell leukemia-1 (MCL1) mRNA splicing mediated by epithelial splicing regulatory protein 1 (ESRP1) in glioma U251 cell lines. METHODS: Data mining was performed in glioma patient database to find out the key sites from MCL1 sequencing results. Exogenous ESRP1 was over-expressed in U251 cells via pcDNA-ESRP1 vector. The levels of different MCL1 isoforms were detected by reverse transcription PCR and Western blotting. RESULTS: The mRNA and protein level of endogenous ESRP1 was lower in U251 cells than in normal gliocytes. The level of MCL1 isoform 1 was higher, while isoform 2 and 3 were lower in U251 cells than in normal gliocytes. Furthermore, MCL1 isoform 1 was reduced and isoform 3 was up-regulated in U251 cells after ESRP1 over-expression. Isoform 2 was unchanged obviously. Finally, MCL1 with the deletion of 801G and 802A sites could not be correctly spliced by ESRP1 and no significant difference was seen in the expressions of isoform 1 and 3 in mutant MCL1. CONCLUSION: Repression of ESRP1 expression or mutation in its RNA recognized sites in tumor results in the abnormality of transcript splicing of oncogenes.

Risk factors associated with sleep disturbance following traumatic brain injury: clinical findings and questionnaire based study.

BACKGROUND: Sleep disturbance is very common following traumatic brain injury (TBI), which may initiate or exacerbate a variety of co-morbidities and negatively impact rehabilitative treatments. To date, there are paradoxical reports regarding the associations between inherent characteristics of TBI and sleep disturbance in TBI population. The current study was designed to explore the relationship between the presence of sleep disturbance and characteristics of TBI and identify the factors which are closely related to the presence of sleep disturbance in TBI population. METHODS: 98 TBI patients (72 males, mean age ± SD, 47 ± 13 years, range 18-70) were recruited. Severity of TBI was evaluated based on Glasgow Coma Scale (GCS). All participants performed cranial computed tomography and were examined on self-reported sleep quality, anxiety, and depression. RESULTS: TBI was mild in 69 (70%), moderate in 15 (15%) and severe in 14 (15%) patients. 37 of 98 patients (38%) reported sleep disturbance following TBI. Insomnia was diagnosed in 28 patients (29%) and post-traumatic hypersomnia in 9 patients (9%). In TBI with insomnia group, 5 patients (18%) complained of difficulty falling asleep only, 8 patients (29%) had difficulty maintaining sleep without difficulty in initial sleep and 15 patients (53%) presented both difficulty falling asleep and difficulty maintaining sleep. Risk factors associated with insomnia were headache and/or dizziness and more symptoms of anxiety and depression rather than GCS. In contrast, GCS was independently associated with the presence of hypersomnia following TBI. Furthermore, there was no evidence of an association between locations of brain injury and the presence of sleep disturbance after TBI. CONCLUSION: Our data support and contribute to a growing body of evidence which indicates that TBI patients with insomnia are prone to suffer from concomitant headache and/or dizziness, report more symptoms of anxiety and depression and severe TBI patients are likely to experience hypersomnia.

[Effects of adipose-derived stem cells-hyaluronic acid composite on healing of wound combined with radiation injury].

OBJECTIVE: To observe and explore the effects of adipose-derived stem cells (ADSCs)-hyaluronic acid (HA) composite on healing of wound combined with radiation injury. METHODS: The ADSCs were harvested from the fat tissue in groin of 10 inbred Sprague Dawley (SD) rats and were isolated and cultured by enzyme digestion. The ADSCs-HA composite was prepared with ADSCs (5 x 10(6) cells/mL) at passage 6 and HA (10 mg/mL). Thirty inbred SD rats, 15 males and 15 females, were randomly divided into groups A (n = 10), B (n = 10), and C (n = 10). A 2 cm x 2 cm full-thickness skin defect was made on the rat back before 20 Gy 60Co radiation exposure. One week after debridement, wounds were treated by petrolatum gauze in group A as the control group, by HA (0.4 mL) and petrolatum gauze in group B, and by ADSCs-HA composite (0.4 mL) and petrolatum gauze in group C. The microvessel density (MVD) and the distribution of CD90 positive cells were observed at 1st, 2nd, 3rd, and 4th weeks. RESULTS: The wound healing was slower, and wound did not heal at 4th week and still filled with granulation tissue in group A; the wound healing of group B was faster than that of group A, and the wound did not heal completely with depression in the center at 4th week; the wound healed completely with epidermilizated surface and no obvious depression at 4th week in group C. The histological observation showed that MVD was significantly higher in group C than in groups A and B at the 1st, 2nd, and 3rd weeks (P < 0.05), and in group B than in group A at the 3rd week (P < 0.05); MVD was significantly higher in groups B and C than in group A (P < 0.05), but no significant difference was found between groups B and C (P > 0.05) at 4th week. No CD90 positive cell was found in groups A and B; CD 90 positive cells were observed in group C and gradually decreased with time. CONCLUSION: ADSCs-HA composite can accelerate healing of wound combined with radiation injury by promoting and controlling wound angiogenesis.