Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis.

Sepsis-associated encephalopathy (SAE) manifested clinically in acute and long-term cognitive impairments and associated with increased morbidity and mortality worldwide. The potential pathological changes of SAE are complex and remain to be elucidated. Pyroptosis, a novel programmed cell death, is executed by caspase-1-cleaved GSDMD N-terminal (GSDMD-NT) and we investigated it in peripheral blood immunocytes of septic patients previously. Here, a caspase-1 inhibitor VX765 was treated with CLP-induced septic mice. Novel object recognition test indicated that VX765 treatment reversed cognitive dysfunction in septic mice. Elevated plus maze, tail suspension test and open field test revealed that depressive-like behaviors of septic mice were relieved. Inhibited caspase-1 suppressed the expressions of GSDMD and its cleavage form GSDMD-NT, and reduced pyroptosis in brain at day 1 and day 7 after sepsis. Meantime, inhibited caspase-1 mitigated the expressions of IL-1ß, MCP-1 and TNF-α in serum and brain, diminished microglia activation in septic mice, and reduced sepsis-induced brain-blood barrier disruption and ultrastructure damages in brain as well. Inhibited caspase-1 protected the synapse plasticity and preserved long-term potential, which may be the possible mechanism of cognitive functions protective effects of septic mice. In conclusion, caspase-1 inhibition exerts brain-protective effects against SAE and cognitive impairments in a mouse model of sepsis.

Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.

Trauma care system in China.

With the development of modern society, high-energy trauma has become an increasing tendency, which brings a great challenge for trauma care. A well-running trauma care system that is composed by pre-hospital and in-hospital care has been proved to decrease the death and disability rate of trauma patients. However, establishment of trauma care system in China is still at the initial stage. Trauma care systems in China and developed countries represented by the United States and Germany are introduced respectively in this article. Construction of regional and hierarchical trauma center, training of specific trauma care team and performance of integrative trauma rescue model are recommended in China.

Current trauma care system and trauma care training in China.

Trauma is a life-threatening "modern disease". The outcomes could only be optimized by cost-efficient and prompt trauma care, which embarks on the improvement of essential capacities and conceptual revolution in addition to the disruptive innovation of the trauma care system. According to experiences from the developed countries, systematic trauma care training is the cornerstone of the generalization and the improvement on the trauma care, such as the Advance Trauma Life Support (ATLS). Currently, the pre-hospital emergency medical services (EMS) has been one of the essential elements of infrastructure of health services in China, which is also fundamental to the trauma care system. Hereby, the China Trauma Care Training (CTCT) with independent intellectual property rights has been initiated and launched by the Chinese Trauma Surgeon Association to extend the up-to-date concepts and techniques in the field of trauma care as well to reinforce the generally well-accepted standardized protocols in the practices. This article reviews the current status of the trauma care system as well as the trauma care training.

Early intramedullary nailing for femoral fractures in patients with severe thoracic trauma: A systemic review and meta-analysis.

PURPOSE: Early intramedullary nailing (IMN) within the first 24 h for multiply injured patients with femoral fracture and concomitant thoracic trauma is controversial. Previously published studies have been limited in size and their outcomes have been inconclusive. A meta-analysis was conducted to evaluate the available data in order to guide care and help improve the outcomes for these patients. METHODS: We searched the literature up to December 2011 in the main medical search engines and identified 6 retrospective cohort studies that explored the safety of early IMN in patients with both femoral fracture and chest injury. Our primary outcome was the rates of pulmonary complication (pneumonia, adult respiratory distress syndrome, fat embolism syndrome), multiple organ failure (MOF) and mortality. RESULTS: We found no statistically significant difference in the rate of pulmonary complications, MOF or mortality in the patients treated with early IMN. CONCLUSION: Early IMN for femoral fractures does not increase the mortality and morbidity in chest- injured patients in the studies analyzed.

Cyclooxygenase-2 blockade inhibits accumulation and function of myeloid-derived suppressor cells and restores T cell response after traumatic stress.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 (Cox-2) contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD11b+/Gr-1+ cells, proliferation and apoptosis of CD4+ T cells were determined. Arginase activity and arginase-1 (Arg-1) protein expression of splenic CD11b+/Gr-1+ cells, and delayed-type hypersensitivity (DTH) response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD11b+/Gr-1+ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD11b+/Gr-1+ cells. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4+ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.

[The influence of oxygen partial pressure change and vascularization of rabbit wound through negative pressure wound therapy].

OBJECTIVE: To investigate the effect of vacuum sealing drainage (VSD) on variation of oxygen partial pressure (PtO2) and vascularization. METHODS: The 12 cases of rabbit's wound models were undergoing the VSD (vacuum group, n = 6) or conventional therapy (conventional group, n = 6). Variation of PtO2 was measured by oxygen partial pressure admeasuring apparatus, expression of hypoxia inducible factor 1α (HIF-1α) mRNA was measured by real-time fluorescent quantitative PCR, content of vascular endothelial growth factor (VEGF) was measured by ELISA after tissue homogenate in 7 days. Vascular endothelial cell (VEC) and new blood capillary (NBC) of hematoxylin-eosin slice of tissue were counted by using light microscope. RESULTS: Average value of PtO2 of vacuum group was significant lower than conventional group (t = -99.780 to -5.305, P < 0.01). Expression of HIF-1α (30 minutes, 1, 6, 12 hours were 3.11 ± 0.07, 3.68 ± 0.26, 4.16 ± 0.13 and 3.91 ± 0.26 respectively) and content of VEGF (30 minutes, 1, 6, 12 hours were 103.3 ± 2.4, 134.2 ± 9.0, 167.8 ± 3.8 and 232.1 ± 9.5 respectively) of vacuum group were increased after 30 minutes and significant lower than conventional group (t = 13.038 - 80.208, P < 0.01), and both of them were reduced after 24 hours (P < 0.05). Counting numbers of VEC (2.47 ± 0.45 to 4.70 ± 0.38) and NBC (1.33 ± 0.49 to 4.33 ± 0.68) of vacuum group were increased at the same time-point and significant higher than conventional group (t = -0.670 to 16.500, P < 0.05). CONCLUSIONS: PtO2 of wound surface could be reduced significantly by VSD. Expression of HIF-1α and content of VEGF were increased by VSD for enhancing differentiated state of VEC and construction of NBC, which were better for vascularization and wound healing.

Inhibition of the C3a receptor attenuates sepsis-induced acute lung injury by suppressing pyroptosis of the pulmonary vascular endothelial cells.

Acute lung injury (ALI) is the leading cause of bacterial sepsis-related death because of disrupted pulmonary endothelial barrier, resulting in protein-rich pulmonary oedema, an influx of pro-inflammatory cells and refractory hypoxaemia. Several studies have reported that C3a levels are significantly higher in organs with sepsis and their peripheral organs and are closely associated with organ dysfunction and poor prognosis in sepsis. However, the role of the C3a complement in sepsis ALI remains unclear. Therefore, this study aimed to investigate the important role and mechanism of C3a in preventing the occurrence of pyroptosis (a pro-inflammatory form of cell death) to protect the lung endothelial cells (ECs) in sepsis-induced ALI. A septic mouse model was established with cecal ligation and puncture (CLP), which demonstrated that C3a mediated EC pyroptosis through its C3aR receptor. Furthermore, inhibition of the C3a-C3aR axis could block both NLRP3/caspase-1 and caspase-11 pathways, thus preventing pulmonary EC from pyroptosis. These results indicate that inhibition of the C3A-C3AR complement axis can inhibit pulmonary vascular EC pyroptosis, a potential target for the treatment of ALI.

Analysis of misdiagnosis in patients with multiple trauma.

OBJECTIVE: To explore the features, treatment outcomes and reasons for misdiagnosis in patients with multiple trauma, so as to decrease the incidence of misdiagnosis. METHODS: A total of 3 163 patients with multiple trauma who were admitted in our department from August 1997 to August 2008, were retrospectively studied to compare the features of diagnosis and treatment. There were 2 117 males (66.93%) and 1 046 females (33.07%) with the mean age of 36.46 years (range, 14-80 years). Parameters such as general status, traumatic condition, diagnosis and treatment situation, prognosis and mortality were analyzed. The differences between misdiagnosis group and correct diagnosis group were compared in terms of severity of injury, complications and treatment outcomes to elucidate the cause and prevention of misdiagnosis. RESULTS: The misdiagnosis rate of multiple trauma in this study was 16.19%. The major anatomic sites misdiagnosed were limbs and pelvis (299 positions, 39.50%), abdominal region and pelvic organ (148 positions, 19.55%), and thoracic region (109 positions, 14.40%). In misdiagnosis group, ISS, length of hospital stay, rates of disturbance of consciousness, critical cases and shock cases were 33.78+/-19.64, (23.59+/-7.26) days, 49.22%, 33.01% and 47.46%, respectively, which were significantly higher than those of the correct diagnosis group (P less than 0.01). And the data showed that the more serious the injury was, the higher the rate of misdiagnosis would be. The rate of primary diagnosis by trauma surgeons in correct diagnosis group was 75.78%, significantly higher than that of the misdiagnosis group (X(2) equal to 382.01, P less than 0.01). The mortality rate of the misdiagnosis group was 2.93%, which was significantly higher than that for all patients (X(2) equal to 5.22, P less than 0.05). CONCLUSIONS: The results indicated that patients with severe multiple trauma are at high risk of misdiagnosis in early treatment. The mortality rate of misdiagnosed patients is higher than the correctly-diagnosed patients. To prevent misdiagnosis, physicians need to take great care to conduct thorough clinical examinations and repeated evaluation.

Modified lumbopelvic fixation for sacral and L5 fractures associated with spinopelvic instability: a case report and introduction of the surgical technique.

Posterior lumbopelvic fixation with iliac screws is the most commonly used method for unstable spinopelvic injuries. It has certain limitations including inability to use distraction along the spinopelvic rod as an indirect reduction maneuver, need for complex 3-dimensional rod contouring and complications such as hardware prominence and soft tissue coverage. In the present case report, we described a surgical technique of lumbopelvic fixation with sacral alar screws for traumatic spinopelvic instability resulted from a unilateral Denis-III comminuted sacral fracture and the L5 burst fracture. On the opposite side of the sacral fracture, caudal screws were implanted into the pedicle of the S1, whereas on the side of sacral fracture, two sacral alar screws were placed parallel to the superior sacral endplate as well as the plane of sacroiliac joint. In addition, horizontal stabilization was conducted with cross-link connections to maintain the longitudinal traction. For sacral fracture associated with traumatic spinopelvic instability, this modified lumbopelvic fixation technique using sacral alar screws makes longitudinal reduction easier, requires less rod contouring, and reduces hardware prominence without compromising the stability.

Cross-sectional study of the educational background and trauma knowledge of trainees in the "China trauma care training" program.

BACKGROUND: Since the trauma knowledge of trauma providers correlates with the outcomes of injured patients, this study aims to assess the socio-demographic characteristics and levels of trauma knowledge of trainees in the China trauma care training (CTCT) program in addition to their post-course test results to provide support for the development of trauma care training programs and trauma systems in China. METHODS: A cross-sectional study was conducted by collecting demographic information, hospital-related information and trauma knowledge of the trainees from 19 regions in China. All participants were assessed by questionnaires collecting the socio-demographic data, the trauma care knowledge levels and the information of the hospitals. RESULTS: There were 955 males (78.9%) and 256 females (21.1%) enrolled. Among them, 854 were physicians (70.5%), 357 were registered nurses (29.5%). In addition, 64 of them also played an administrative role in the hospitals (5.3%). The score of the trainees who were members of the emergency department staff (72.59 ± 14.13) was the highest among the scores of all the personnel surveyed, followed by those of the trainees from the intensive care unit (ICU) (71.17 ± 12.72), trauma surgery department (67.26 ± 13.81), orthopedics department (70.36 ± 14.48), general surgery department (69.91 ± 14.79) and other departments (69.93 ± 16.91), P = 0.031. The score of the professors (73.09 ± 15.05) was higher than those of the associate professors (72.40 ± 14.71), lecturers (70.07 ± 14.25) and teaching assistants (67.58 ± 15.16), P < 0.0001. The score of the individuals who attended experts' trauma lectures (72.22 ± 14.45) was higher than that of individuals who did not attend the lectures (69.33 ± 15.17), P = 0.001. The mean scores before and after the training were 71.02 ± 14.82 and 84.24 ± 13.77, respectively, P < 0.001. The mean score of trauma knowledge after the training of trainees from different provinces and with different educational backgrounds was higher than that before the training, with a statistically significant difference (P < 0.05). CONCLUSIONS: The level of trauma knowledge of trauma care providers was associated with their department, professional position and previous participation in related academic conferences. Trauma care experience and participation in academic lectures and training program including CTCT may effectively improve individuals' level of trauma knowledge.

Morin exerts protective effects on encephalopathy and sepsis-associated cognitive functions in a murine sepsis model.

Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3ß activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aß deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments.

FK866 attenuates sepsis-induced acute lung injury through c-jun-N-terminal kinase (JNK)-dependent autophagy.

AIMS: Increasing evidence indicates that FK866, a specific noncompetitive nicotinamide phosphoribosyl transferase inhibitor, exhibits a protective effect on acute lung injury (ALI). Autophagy plays a pivotal role in sepsis-induced ALI. However, the contribution of autophagy and the underlying mechanism by which FK866-confered lung protection remains elusive. Herein, we aimed to study whether FK866 could alleviate sepsis-induced ALI via the JNK-dependent autophagy. MAIN METHODS: Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) to establish the polymicrobial sepsis mice model, and treated with FK866 (10 mg/kg) at 24, 12 and 0.5 h before the CLP procedure. The lung protective effects were measured by lung histopathology, tissue edema, vascular leakage, inflammation infiltration, autophagy-related protein expression and JNK activity. A549 cells were stimulated with LPS (1000 ng/ml) to generate the ALI cell model, and pretreated with FK866 or SP600125 for 30 min to measure the autophagy-related protein expression and JNK activity. KEY FINDINGS: Our results demonstrated that FK866 reduced lung injury score, tissue edema, vascular leakage, and inflammatory infiltration, and upregulated autophagy. The protective effect of autophagy conferred by FK866 on ALI was further clarified by using 3-methyladenine (3MA) and rapamycin. Additionally, the activity of JNK was suppressed by FK866, and inhibition of JNK promoted autophagy and showed a benefit effect. SIGNIFICANCE: Our study indicates that FK866 protects against sepsis-induced ALI by induction of JNK-dependent autophagy. This may provide new insights into the functional mechanism of NAMPT inhibition in sepsis-induced ALI.

Influence of operative timing on prognosis of patients with acute subdural hematoma.

OBJECTIVE: To study the influence of operative timing on the prognosis of patients with acute subdural hematoma (ASDH) in order to provide theoretical basis for clinical treatment. METHODS: The clinical data of 202 patients with ASDH undergoing operations were collected, and the mortalities and functional survival rates were analyzed 2, 4, 6, and 8 hours after injury. RESULTS: No significant difference was found in mortalities and functional survival rates at different operative timings. However, there was a clear trend that the shorter the operative timing was, the lower the mortality and the higher functional survival rate were. In addition, the mean time from injury to operation of non-survivors was significantly longer than that of survivors. CONCLUSIONS: Operative timing has potential influences on the prognosis of patients with ASDH. Surgical evacuation of ASDH should be performed as soon as possible once the operation indication emerges.

Variation and significance of NKT cell and its subset in patients with severe multiple injuries.

OBJECTIVE: To observe the variation and significance of natural killer T (NKT) cells in patients with severe multiple injuries. METHODS: Peripheral blood was drawn from 30 patients with severe multiple injuries and 20 healthy individuals. NKT cells and the subsets of NKT cells were stained and analyzed on fluorescence activated cell sorter (FACS) using Cellquest software. The level of IL-4 and IFN-gamma in blood serum was detected by ELISA. RESULTS: The proportion of NKT cells was significantly increased. CD4+ NKT cells was increased (t equal to -3.11, P less than 0.01) and CD4+CD8+NKT (double negative NKT, DN NKT) cells decreased in patients with severe multiple injuries compared with healthy controls (t equal to 2.99, P less than 0.01). There was a positive correlation between the proportion of NKT cells and injury severity score (ISS) by Spearman correlation analysis (r equal to 0.70, P less than 0. 01). The level of IFN-gamma was significantly decreased and the level of IL-4 significantly increased in patients with severe multiple injuries. CONCLUSIONS: We demonstrate that human NKT cells are increased in trauma patients. Most significantly, there is an association between ISS and NKT cells. The increased CD4+NKT cells may contribute to the reduction of Th1 cytokine production and the growth of Th2 cytokine production, leading to the suppression of immunity after injury.

[Expression of soluble human triggering receptors on myeloid cell-1 in patients with multiple trauma and its clinical significance].

OBJECTIVE: To investigate the expression profile of human soluble triggering receptor on myeloid cell-1 (sTREM-1) in patients with multiple trauma and determine its clinical significance. METHODS: Peripheral blood of 52 patients admitted to the hospital from October 2007 to January 2008 with multiple traumas with injury severity score (ISS) > or = 16 and 7 healthy volunteers were obtained, and sera samples were isolated. sTREM-1 was determined by semi-quantitative immunoblot technique. TNF-alpha and C-reactive protein (CRP) were determined by ELISA. RESULTS: sTREM-1 of patients with multiple traumas was significantly increased as compared with that of control (P < 0.001), and sTREM-1 of ISS > or = 25 group was significantly higher than that of 16 < or = ISS < 25 group (P < 0.05). sTREM-1 level correlated closely with TNF-alpha level (r = 0.845, P < 0.05), but did not correlate with CRP (r = 0.426, P > 0.05). In patients with sepsis, sTREM-1 on 1, 2 and 7 d was (25.1 +/- 2.2), (31.9 +/- 2.6) and (25.2 +/- 1.9) ng/L, respectively. In patients without sepsis, sTREM-1 on 1, 2 and 7 d was (15.8 +/- 1.3), (24.2 +/- 2.0) and (13.9 +/- 1.5) ng/L, respectively. sTREM-1 of patients with sepsis was significantly higher than that of patients without sepsis (P < 0.05). CONCLUSIONS: Serum sTREM-1 correlates closely with ISS, TNF-alpha and onset of sepsis, indicating that it may play an important role in the development of sepsis in patients with multiple traumas.

Dihydromyricetin Alleviates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis in Mice Model.

Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed cell death, is linked to acute lung injury (ALI). Dihydromyricetin (DHM) has been reported to exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in vascular endothelial cells. However, the effects of DHM on NLRP3 inflammasome-induced pyroptosis in ALI remain elusive. In the present study, male BALB/c mice were subjected to cecal ligation and puncture (CLP), and DHM (50, 100, 150 mg/kg) was orally administered (once per day, for 3 days) 2 h after CLP. After 72 h, lung histopathology was examined, and the wet/dry (W/D) ratio, inflammatory infiltration, total protein concentration, total cell, and neutrophil counts were detected. Myeloperoxidase (MPO), interleukin (IL)-6, TNF-α, IL-1ß, and IL-18 levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Additionally, the expression of NLRP3 signaling pathway proteins were detected by Western blotting. The results revealed that in BALF, DHM (150 mg/kg) treatment significantly reduced the CLP-induced lung histopathological injury, inflammatory cell infiltration, total cell and neutrophil number, and total protein and albumin concentration. DHM treatment significantly inhibited the CLP-induced NLRP3 inflammasome pathway (NLRP3, ASC, caspase-1, gasdermin D (Gsdmd), IL-1ß, and IL-18). In conclusion, these results demonstrate that DHM protects against CLP-induced ALI by inhibiting NLRP3 inflammasome activation and subsequent pyroptosis.

MMP-1 Over-expression Promotes Malignancy and Stem-Like Properties of Human Osteosarcoma MG-63 Cells In Vitro.

Osteosarcoma is the most common primary malignant bone tumor in childhood, and it maintains a high level of recurrence. Matrix metalloproteinase-1 (MMP-1) was found to contribute to cancer progression. The present study was to investigate the in vitro effects of MMP-1 over-expression on the proliferation, invasion, metastasis and stem-like properties of osteosarcoma MG-63 cells. The MG-63 cells were cultured and had a full length MMP-1 cDNA inserted by the lentiviral vector (MG-63MMP-1+). MG-63 negative control and MG-63 blank control groups were established as well. MMP-1 expression was detected in MG-63MMP-1+, MG-63 negative control and MG-63 blank control cells using qPCR, Western blotting and immunofluorescence after 24 h of culture. The cell proliferation assay was performed with a camera attached to a bioreactor, which was programmed to photograph five regions of each well every 10 min over a period of 48 h. The cell invasion assay was conducted with Matrigel to assess the invasive potential of MG-63 cells over 24 h, the qPCR analysis to measure stem cell markers, including Oct4, Sox-2, Nanog, and Pax-7, and Western blot analysis to detect invasive and metastatic potential markers TIMP-1, VEGF and BMP2/4, after 24 h of culture. Immunofluorescence was used to investigate the presence of the stem cell marker Pax-7 after 24-h culture. The results showed that over-expression of MMP-1 after transfection could significantly increase tumor cell proliferation and invasion (P<0.05, MG-63MMP-1+versus controls). Pax-7 was highly expressed in MG-63MMP-1+ cells, with no significant changes of Oct-4, Sox-2, and Nanog observed (P<0.05). MG-63MMP-1+ cells showed higher expression of VEGF and BMP 2/4 proteins and lower expression of TIMP-1 protein than controls (P<0.05). It was concluded that MMP-1 over-expression in MG-63 cells contributed to the proliferation, invasion, metastasis and stem-like properties of osteosarcoma cells. Future studies should focus on in vivo effects of MMP-1 over-expression and the application of MMP-1 and Pax-7 inhibition in vivo to osteosarcoma therapies.

Caspase-1-dependent pyroptosis of peripheral blood mononuclear cells predicts the development of sepsis in severe trauma patients: A prospective observational study.

Pyroptosis plays a pivotal role in sepsis and septic shock in animal studies. However, its clinical significance in pathological conditions has not been well elucidated. This study aimed to evaluate the correlation between the percentage of pyroptotic peripheral blood mononuclear cells (PBMCs) and the clinical index and to investigate the relationship between PBMCs pyroptosis and the development of sepsis in trauma patients.This prospective study was conducted from October 2016 to May 2017 in a comprehensive trauma center. Sixty trauma patients and 10 healthy controls were enrolled. Peripheral blood samples were collected from the patients within 24 hours after injury. The percentages of pyroptotic and apoptotic PBMCs were measured using flow cytometry, and plasma levels of cytokines were evaluated using flow cytometric analysis with a human inflammation 13-plex panel.Trauma patients who developed sepsis had higher percentages of pyroptotic and apoptotic PBMCs at admission. Patients who developed sepsis (n = 33) had higher interleukin (IL)-6, IL-18, and monocyte chemotactic protein-1 (MCP-1) concentrations at admission than patients (n = 27) who did not develop sepsis. The percentage of PBMCs pyroptosis was significantly correlated with injury severity score (ISS), acute physiology and chronic health evaluation (APACHE) II score, IL-10, IL-18, and MCP-1 levels in trauma patients. PBMCs pyroptosis is a better biomarker in predicting the development of sepsis after trauma.This study indicates that the percentage of pyroptotic PBMCs increases during the early phase of trauma and that this increase is significantly correlated with the severity and state of inflammation in trauma patients. PBMCs pyroptosis is a potential marker for predicting the development of sepsis after trauma.

[Analysis of emergency treatment in 4519 patients with multiple injuries].

OBJECTIVE: To investigate the clinical manifestations, treatment, complications, and prognosis of patients with multiple injuries. METHOD: The clinical data, including the causes of injury, treatment, complications, causes of death, and mortality rate, of 4519 patients were retrospectively analyzed. RESULTS: The major causes of injury were road traffic injury (2410 cases, 53.33%), violence injury (747 cases, 16.53%), and high falling injury (575 cases, 12.72%). The main involved positions included head (2247 cases, 18.71%), abdominal region and pelvis (2118 cases, 17.64%), and thoracic region (1853 cases, 15.43%). The major complications were shock (1497 cases, 33.13%). The main cause of death was sepsis with multiple organ dysfunction syndrome/failure (28 cases, 82.35%) after multiple injuries, significant higher than other causes in the same period (P<0.01). CONCLUSIONS: The multiple injuries have various causes of disease, and were complicated with their diverse clinical manifestations, numerous complications, and high mortalities. Further research on the integrated rescue mortality is required.