Time to maximum amplitude of thromboelastography can predict mortality in patients with severe COVID-19: a retrospective observational study.

Objective: To predict mortality in severe patients with COVID-19 at admission to the intensive care unit (ICU) using thromboelastography (TEG). Methods: This retrospective, two-center, observational study involved 87 patients with PCR-and chest CT-confirmed severe COVID-19 who were admitted to at Wuhan Huoshenshan Hospital and the 908th Hospital of Chinese PLA Logistic Support Force between February 2020 and February 2023. Clinic demographics, laboratory results, and outcomes were compared between those who survived and those who died during hospitalization. Results: Thromboelastography showed that of the 87 patients, 14 were in a hypercoagulable state, 25 were in a hypocoagulable state, and 48 were normal, based on the time to maximum amplitude (TMA). Patients who died showed significantly lower α angle, but significantly longer R-time, K-time and TMA than patients who survived. Random forest selection showed that K-time, TMA, prothrombin time (PT), international normalized ratio (INR), D-dimer, C-reactive protein (CRP), aspartate aminotransferase (AST), and total bilirubin (Tbil) were significant predictors. Multivariate logistic regression identified that TMA and CRP were independently associated with mortality. TMA had a greater predictive power than CRP levels based on time-dependent AUCs. Patients with TMA ≥ 26.4 min were at significantly higher risk of mortality (hazard ratio 3.99, 95% Confidence Interval, 1.92-8.27, p < 0.01). Conclusion: TMA ≥26.4 min at admission to ICU may be an independent predictor of in-hospital mortality for patients with severe COVID-19.

Translation and validation of traditional Chinese version of the pediatric eating assessment Tool-10.

BACKGROUND: /Purpose: The Pediatric Eating Assessment Tool-10 (Pedi-EAT-10) is a caregiver-administrated subjective questionnaire for evaluating swallowing and feeding disorders among children. This study translated the Pedi-EAT-10 into Traditional Chinese and tested the translated version's reliability and validity. METHODS: Pedi-EAT-10 was translated into Traditional Chinese by experts and finalized after discussion and testing. A total of 168 participants, consisting of 32 children with dysphagia from a tertiary medical center and 136 healthy controls from its Children Care Center for Employees, were recruited. All participants were assessed by an otolaryngologist and speech-language pathologist. The reliability, validity, and efficacy of the translated Pedi-EAT-10 were analyzed to ensure it could be used to identify pediatric dysphagia and feeding problems. RESULTS: The Traditional Chinese version of the Pedi-EAT-10 had significant clinical discriminative validity between the dysphagia group and the control group (total score = 9.6 vs. 2.6, P < 0.001), acceptable test-retest reliability (intraclass correlation = 0.63), and excellent internal consistency (Cronbach's α = 0.91 for the entire cohort). The overall performance of the test for distinguishing children with dysphagia from normal controls was acceptable, and the area under the curve was 74.8% (sensitivity = 71.9%; specificity = 69.9%). The optimal cutoff score was ≥3 on the Youdex index. CONCLUSIONS: The Traditional Chinese version of the Pedi-EAT-10 has fair reliability and validity and can be quickly and easily completed by caregivers. The translated Ped-EAT-10 can be used as a first-line tool for assessing the need for further referral and instrumental examination.

Carbonized Cellulose Aerogel Derived from Waste Pomelo Peel for Rapid Hemostasis of Trauma-Induced Bleeding.

Uncontrollable massive bleeding caused by trauma will cause the patient to lose a large amount of blood and drop body temperature quickly, resulting in hemorrhagic shock. This study aims to develop a hemostatic product for hemorrhage management. In this study, waste pomelo peel as raw material is chosen. It underwent processes of carbonization, purification, and freeze-drying. The obtained carbonized pomelo peel (CPP) is hydrophilic and exhibits a porous structure (nearly 80% porosity). The water/blood absorption ratio is significantly faster than the commercial Gelfoam and has a similar water/blood absorption capacity. In addition, the CPP showed a water-triggered shape-recoverable ability. Moreover, the CPP shows ideal cytocompatibility and blood compatibility in vitro and favorable tissue compatibility after long terms of subcutaneous implantation. Furthermore, CPP can absorb red blood cells and fibrin. It also can absorb platelets and activate platelets, and it is capable of achieving rapid hemostasis on the rat tail amputation and hepatectomized hemorrhage model. In addition, the CPP not only can quickly stop bleeding in the rat liver-perforation and rabbit heart uncontrolled hemorrhage models, but also promotes rat liver and rabbit heart tissue regeneration in situ. These results suggest the CPP has shown great potential for managing uncontrolled hemorrhage.

A newly proposed heatstroke-induced coagulopathy score in patients with heat illness: A multicenter retrospective study in China.

PURPOSE: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC. METHODS: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0. RESULTS: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05). CONCLUSIONS: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.

Nomogram for predicting disseminated intravascular coagulation in heatstroke patients: A 10 years retrospective study.

Background: Disseminated intravascular coagulation (DIC) can lead to multiple organ failure and death in patients with heatstroke. This study aimed to identify independent risk factors of DIC and construct a predictive model for clinical application. Methods: This retrospective study included 87 patients with heatstroke who were treated in the intensive care unit of our hospital from May 2012 to October 2022. Patients were divided into those with DIC (n = 23) or without DIC (n = 64). Clinical and hematological factors associated with DIC were identified using a random forest model, least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE). Overlapping factors were used to develop a nomogram model, which was diagnostically validated. Survival at 30 days after admission was compared between patients with or without DIC using Kaplan-Meier analysis. Results: Random forest, LASSO, and SVM-RFE identified a low maximum amplitude, decreased albumin level, high creatinine level, increased total bilirubin, and aspartate transaminase (AST) level as risk factors for DIC. Principal component analysis confirmed that these independent variables differentiated between patients who experienced DIC or not, so they were used to construct a nomogram. The nomogram showed good predictive power, with an area under the receiver operating characteristic curve of 0.976 (95% CI 0.948-1.000) and 0.971 (95% CI, 0.914-0.989) in the internal validation. Decision curve analysis indicated clinical utility for the nomogram. DIC was associated with significantly lower 30 days survival for heatstroke patients. Conclusion: A nomogram incorporating coagulation-related risk factors can predict DIC in patients with heatstroke and may be useful in clinical decision-making.

Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial.

PURPOSE: Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP. METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission. RESULTS: A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). CONCLUSION: The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

Thromboelastography maximum amplitude as an early predictor of disseminated intravascular coagulation in patients with heatstroke.

OBJECTIVES: The aim of this study was to investigate the ability of TEG to predict DIC associated with heatstroke. METHODS: We carried out a retrospective, single-center study of 67 patients with heatstroke admitted to an intensive care unit (ICU) at a comprehensive hospital between July 2016 and August 2021. Conventional coagulation tests (CCTs) and TEG were performed within 2 h of admission in ICU. Patients were diagnosed with DIC based on International Society of Thrombosis and Hemostasis criteria, and those with or without DIC were compared in terms of CCTs and TEG findings. The ability of individual parameters to predict DIC was assessed based on logistic regression and the area under receiver operating characteristic curves (AUC). RESULTS: Of the 67 patients, 19 (28.4%) were diagnosed with DIC. Compared to patients without DIC, those with DIC had significantly longer reaction time [14.5(10.6-26.0) vs. 6.2(5.1-10.1)min](p < 0.001) and kinetic time [10.9(5.9-25.0) vs. 2.7(2.2-4.7) min](p < 0.001). Conversely, those with DIC had significantly lower alpha angle [22(9.1-43.3) vs. 55.0(44.8-61.7)°](p < 0.001), maximum amplitude (MA) [(26.9(17.7-41.4) vs. 52.2(45.8-58.1) mm)] (p < 0.001) and coagulation index [-17.3(-39 to -7.9）vs. -2.4(-6.2to-0.6)](p < 0.001). MA at a cutoff value of 45.4 mm gave an AUC of 0.9 for predicting DIC, with sensitivity of 77.1%, specificity of 89.5%, positive predictive value of 10.5% and negative predictive value of 22.9%. Multifactorial logistic regression identified MA < 45.4 mm as an independent predictor of DIC (odds ratio 9, 95% confidence interval 1.2-69.2, p = 0.035). MA decreased significantly as DIC score increased and was significantly lower in the non-survivors on admission. CONCLUSIONS: MA < 45.4 mm in patients with heatstroke may predict elevated risk of DIC. HighlightsPatients with heatstroke-induced disseminated intravascular coagulation (DIC) has high mortality.A retrospective, single-center study was performed to investigate the ability of thromboelastography (TEG) to predict DIC associated with heatstroke.The maximum amplitude (MA) value of TEG decreased significantly with the increase of DIC score.MA < 45.4 mm was firstly demonstrated to an independent predictor of heatstroke-induced DIC.

Tissue-Type Plasminogen Activator-Inhibitor Complex as an Early Predictor of Septic Shock: A Retrospective, Single-Center Study.

Background: Sepsis can progress to septic shock and death, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study explored whether levels of tissue-type plasminogen activator-inhibitor complex (t-PAIC) in serum can predict septic shock early. Methods: We retrospectively analyzed 311 sepsis patients who had been admitted to the intensive care unit (ICU) at our tertiary care hospital between May 2018 and April 2021, and we divided them into those who progressed to septic shock (n = 203) or not (n = 108) based on sepsis-3 definition. After matching patients in the two groups based on propensity scoring, we screened for risk factors of septic shock using logistic regression. We assessed potential predictors of such shock based on the area under the receiver-operating characteristic curve (AUC), Kaplan-Meier survival curves, and correlation analysis. Results: After propensity score matching to generate two equal groups of 108 patients, we found that serum t-PAIC was significantly higher in septic shock patients. Uni- and multivariate logistic regression identified t-PAIC as an independent risk factor for septic shock (OR 1.14, 95% CI 1.09-1.19, P < 0.001) and a biomarker that predicted it with an AUC up to 0.875 (95% CI, 0.829-0.920). Based on the optimal cut-off of t-PAIC = 17.9 ng/mL, we found that patients at or above this threshold had significantly higher lactate levels and scores on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA). Such patients also had significantly worse survival (HR 2.4, 95% CI 1.38-4.34, P = 0.004). Spearman's correlation coefficients were 0.66 between t-PAIC and lactate, and 0.52 between t-PAIC and SOFA. Conclusions: Serum levels of t-PAIC may be an independent risk factor for septic shock, and they may correlate with the severity of such shock.

Association of platelet count with mortality in patients with infectious diseases in intensive care unit: a multicenter retrospective cohort study.

Platelets play important roles in thrombosis, hemostasis, inflammation, and infection. We aimed to evaluate the association between platelet count and its variation trend and prognosis of patient with infectious diseases in intensive care units (ICUs). This retrospective cohort study extracted 4,251 critically ill adult patients with infectious diseases from the eICU Collaborative Research Database, whose platelet counts were measured daily during the first 7 days after admission. In the survivors, platelet counts decreased in the first days after admission, reached a nadir on day 3, and then returned and continued to rise above the admission value. In non-survivors, the platelet counts decreased after admission, without a subsequent upturn. We defined three subgroups according to the nadir platelet counts within 7 days: ≤50, 50-130, and ≥130 × 109/L, corresponding to high, intermediate, and low ICU mortality. A decreased platelet count was associated with increased ICU mortality (intermediate vs. low: 1.676 [1.285-2.187]; high vs. low: 3.632 [2.611-5.052]). In conclusion, during the first 7 days, platelet counts decreased after ICU admission, while increased subsequently in the survivors but not in the non-survivors. ICU mortality risk increased as nadir platelet count decreased below 130 × 109/L, and further boosted when it reached below 50 × 109/L.

Prediction of 90-Day Mortality among Sepsis Patients Based on a Nomogram Integrating Diverse Clinical Indices.

BACKGROUND: Sepsis is prevalent among intensive care units and is a frequent cause of death. Several studies have identified individual risk factors or potential predictors of sepsis-associated mortality, without defining an integrated predictive model. The present work was aimed at defining a nomogram for reliably predicting mortality. METHODS: We carried out a retrospective, single-center study based on 231 patients with sepsis who were admitted to our intensive care unit between May 2018 and October 2020. Patients were randomly split into training and validation cohorts. In the training cohort, multivariate logistic regression and a stepwise algorithm were performed to identify risk factors, which were then integrated into a predictive nomogram. Nomogram performance was assessed against the training and validation cohorts based on the area under receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis. RESULTS: Among the 161 patients in the training cohort and 70 patients in the validation cohort, 90-day mortality was 31.6%. Older age and higher values for the international normalized ratio, lactate level, and thrombomodulin level were associated with greater risk of 90-day mortality. The nomogram showed an AUC of 0.810 (95% CI 0.739 to 0.881) in the training cohort and 0.813 (95% CI 0.708 to 0.917) in the validation cohort. The nomogram also performed well based on the calibration curve and decision curve analysis. CONCLUSION: This nomogram may help identify sepsis patients at elevated risk of 90-day mortality, which may help clinicians allocate resources appropriately to improve patient outcomes.

Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy.

Trauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2-85.1% of trauma patients, in whom it can increase the risk of thrombotic events and mortality by 2- to 4-fold. Therefore, the Chinese People's Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.

[Research progress of coagulation dysfunction in coronavirus disease 2019].

The coronavirus disease 2019 (COVID-19) has outbroken globally. As an acute infectious disease, COVID-19 has significant impacts on multiple organs and systems throughout the body. Among patients with COVID-19, especially severe and critical cases, a variety of potential risk factors for coagulation dysfunction exist. Furthermore, the coagulation dysfunction of COVID-19 patients was mainly characterized by elevated D-dimer levels. The coagulation dysfunction could directly affect the prognosis of COVID-19 patients and is a major cause of death in patients with severe COVID-19. In this article, the literatures on the basic clinical manifestations, clinical risk factor, mechanism of coagulation dysfunction and evaluation of coagulation function in COVID-19 were reviewed.

Thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis (TRACE trial): protocol of a multicentre, randomised, double-blind, placebo-controlled, parallel-group trial.

INTRODUCTION: Infected pancreatic necrosis (IPN) and its related septic complications are the major causes of death in patients with acute necrotising pancreatitis (ANP). Therefore, the prevention of IPN is of great clinical value, and immunomodulatory therapy with thymosin alpha 1 may be beneficial. This study was designed to test the hypothesis that the administration of thymosin alpha 1 during the acute phase of ANP will result in a reduced incidence of IPN. METHODS AND ANALYSIS: This is a randomised, multicentre, double-blind, placebo-controlled study. 520 eligible patients with ANP will be randomised in a 1:1 ratio to receive either the thymosin alpha 1 or the placebo using the same mode of administration. The primary endpoint is the incidence of IPN during the index admission. Most of the secondary endpoints will be registered within the index admission including in-hospital mortality, the incidence of new-onset organ failure and new-onset persistent organ failure (respiration, cardiovascular and renal), receipt of new organ support therapy, requirement for drainage or necrosectomy, bleeding requiring intervention, human leucocyte antigens-DR(HLA-DR) on day 0, day 7, day 14, and so on and adverse events. Considering the possibility of readmission, an additional follow-up will be arranged 90 days after enrolment, and IPN and death at day 90 will also be served as secondary outcomes. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (Number 2015NZKY-004-02). The thymosin alpha 1 in the prevention of infected pancreatic necrosis following acute necrotising pancreatitis(TRACE) trial was designed to test the effect of a new therapy focusing on the immune system in preventing secondary infection following ANP. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02473406).

Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19.

Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.

Expert consensus on the diagnosis and treatment of thrombocytopenia in adult critical care patients in China.

Thrombocytopenia is a common complication of critical care patients. The rates of bleeding events and mortality are also significantly increased in critical care patients with thrombocytopenia. Therefore, the Critical Care Medicine Committee of Chinese People's Liberation Army (PLA) worked with Chinese Society of Laboratory Medicine, Chinese Medical Association to develop this consensus to provide guidance for clinical practice. The consensus includes five sections and 27 items: the definition of thrombocytopenia, etiology and pathophysiology, diagnosis and differential diagnosis, treatment and prevention.

Expert consensus on the diagnosis and treatment of heat stroke in China.

Heat stroke (HS) is a fatal disease caused by thermal damage in the body, and it has a very high mortality rate. In 2015, the People's Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China, Expert consensus on standardized diagnosis and treatment for heat stroke. With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years, the 2015 consensus no longer meet the requirements for HS prevention and treatment. It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage, is more practical and is more in line with China's national conditions. This new expert consensus includes new concept of HS, recommendations for laboratory tests and auxiliary examinations, new understanding of diagnosis and differential diagnosis, On-site emergency treatment and In-hospital treatment, translocation of HS patients and prevention of HS.

Successful treatment of toxic epidermal necrolysis using plasmapheresis: A prospective observational study.

Toxic epidermal necrolysis (TEN) is a rare, severe, life-threatening skin disease and it requires urgent critical care, including admission to the intensive care unit (ICU). It is characterized by fatal sequelae and high mortality. Currently, insufficient evidence exists to support the use of any systemic adjuvant therapy, such as cyclophosphamide, intravenous immunoglobulin (IVIg), or corticosteroids. However, plasmapheresis has been increasingly valued by clinicians due to its significant efficacy and little adverse side effects. To assess the efficacy of such treatment, 28 patients who were diagnosed with TEN or SJS/TEN overlap were continuously recruited in the ICU from February 2009 to August 2016. These patients including both children and adults were randomly divided into two groups based on whether or not plasmapheresis therapy was performed after admission, which resulted in a plasmapheresis group (n=13) and a non-plasmapheresis group (n=15). Severity of the disease and the efficacy of treatments were evaluated by the severity-of-illness score for TEN. The results indicated that plasmapheresis may be superior to conventional therapies, such as IVIg or corticosteroids. Furthermore, plasmapheresis combined with other treatments might not be advantageous compared to the effect of plasmapheresis alone.

Inhibition of acid sensing ion channel by ligustrazine on angina model in rat.

Ligustrazine, a compound extracted from roots of Ligusticum chuanxiong, is widely used in Chinese traditional medicine to treat cardiac and cerebrovascular diseases and pain, including angina. The mechanism(s) of ligustrazine's effect to reduce angina is not clear. Angina is mediated by cardiac afferent sensory neurons. These neurons display a large acid-evoked depolarizing sodium current that can initiate action potentials in response to acidification that accompanies myocardial ischemia. Acid-sensing ion channels (ASICs) mediate this current. Here we tested the hypothesis that ligustrazine reduces ischemia-induced cardiac dysfunction and acid-evoked pain by an action to inhibit ASIC-mediated current. The effects of ligustrazine to attenuate ischemia-induced ST-segment depression, T wave changes, and myocardial infarct size in hearts of anesthetized rats were determined. Effects of ligustrazine on currents mediated by ASICs expressed in cultured Chinese hamster ovary cells, and effects of the drug on acid-induced nociceptive behavior and acid-induced currents in isolated dorsal root ganglions cells were measured. Ligustrazine significantly attenuated acid-induced ASIC currents, reduced cardiac ischemia-induced electrical dysfunction and infarct size, and decreased the nociceptive response to injection of acid into the paw of the rat hindlimb. The ASIC channel inhibitor A-317567 similarly reduced electrical dysfunction, infarct size, and nociceptive behavior in the rat. Inhibition of ASICs by ligustrazine may explain at least in part the beneficial effects of the drug that are observed in patients with ischemic heart disease and angina.

Novel biomarkers for early prediction of sepsis-induced disseminated intravascular coagulation in a mouse cecal ligation and puncture model.

INTRODUCTION: The objective of this study was to identify biomarkers of sepsis-induced disseminated intravascular coagulation (DIC) among platelet-derived factors using biotin label-based custom protein microarray technology in a mouse cecal ligation and puncture (CLP) model. METHODS: KM mice were randomized into sham-operated and CLP groups. Blood samples were obtained immediately and at 1 h, 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after establishment of the CLP for platelet count, coagulation assay and blood chemistry. Lung and mesentery tissues were examined histologically at all corresponding time points, looking for microthrombus formation. Serial protein microarray analysis was performed to detect platelet-derived factors. RESULTS: The survival rate 72 h post-CLP was 15%, but there was no mortality among the sham-operated mice. Compared with the sham group, the platelet count (n = 5, p < 0.05), fibrinogen concentration (n = 5, p < 0.05) and alanine aminotransferase level of the CLP group began to decrease significantly at 6 h post-CLP. Significant prolongation of prothrombin time (n = 5, p < 0.05) and activated partial thromboplastin time (n = 5, p < 0.05) and elevation of D-dimer (n = 5, p < 0.05) occurred after 6 h post-CLP. On histology, microthrombus formation in lung and mesentery tissue was observed in the CLP groups 6 h post-CLP and had become significant and extensive 12 h post-CLP (n = 5, p < 0.05). On protein microarray analysis and ELISA, thrombospondin (TSP), tissue inhibitor of metalloproteinase 1 (TIMP-1) and thymus chemokine-1 (TCK-1) all increased during the first 2 h post-CLP, then remained at a higher level than in the sham group for 72 h post-CLP (n = 5, p < 0.05). CONCLUSIONS: TSP, TIMP-1 and TCK-1 are elevated in the early stage of sepsis-induced DIC in a mouse CLP model and may be considered early markers for sepsis-induced DIC.

[The effect of telomerase reverse transcriptase on 5-HT induced pulmonary artery smooth muscle cells proliferation].

OBJECTIVE: To investigate the effect of telomerase reverse transcriptase (TERT) to the proliferation of 5-HT induced pulmonary artery smooth muscle cells (PASMCs). METHODS: The PASMCs proliferation experiment was performed to detect the effort on PASMCs of 5-HT or ASODN TERT (antisense oligoribonucleotides TERT designed according to the rat TERT mRNA sequence of gene bank). The immunohistochemistry staining experiment and the in situ hybridization experiment were to detect the TERT protein and mRNA expression with 5-HT or ASODN TERT. FITC marked ASODN TERT experiment was done to research the distribution of ASODN TERT in PASMCs. RESULTS: 5-HT promoted PASMCs proliferation in a dose-dependent manner (10(-9) - 10(-5) mol/L). 5-HT also significantly increased TERT expression at protein and mRNA levels as shown by immunohistochemistry staining and the in situ hybridization studies. This effect could be blocked by ASODN TERT in a time and dose-dependent manner. CONCLUSIONS: Our experiments show TERT is one of the key factors in the procession of 5-HT induced PASMCs proliferation. ASODN TERT might be a potential therapy agent for pulmonary hypertension.