Acid Promoted Tetrafunctionalization of Terminal Alkynes: Geminal Diazidation and Dibromination.

The synthesis of complex alkanes by the tetrafunctionalization of alkynes is limited and challenging. Herein, an unprecedented efficient geminal diazidation and dibromination of terminal alkynes is developed, which provides novel access to structurally diverse organic azides. The approach has exclusive chemo- and regioselectivity and features mild reaction conditions, good tolerance of various functional groups, and more crucially, no metal involved in the reaction, thereby benefiting the late-stage decoration of medicinal molecules. A mechanistic study showed that the current geminal diazidation and dibromination proceeds via a radical pathway.

Developing an abnormal high-Na-content P2-type layered oxide cathode with near-zero-strain for high-performance sodium-ion batteries.

Layered transition metal oxides (NaxTMO2) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, NaxTMO2 suffer from multiple phase transitions and Na+/vacancy ordering upon Na+ insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g-1 at 0.2C and 97 mA h g-1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na+ storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials.

[Effects of Four Amendments on Fertility and Labile Organic Carbon Fractions of Acid Purple Soil].

The aim of this study was to explore the effects of four amendments on soil fertility and labile carbon fraction characteristics of acid purple soil, so as to provide scientific basis for nutrient management and carbon storage stability in purple soil. Field experiments were carried out, and six treatments were set up:no fertilization (CK), only chemical fertilizer (F), lime + chemical fertilizer (SF), organic fertilizer + chemical fertilizer (OM), biochar + chemical fertilizer (BF), and vinasse biomass ash + chemical fertilizer (JZ). The contents of soil organic matter, pH, available nutrients, soil integrated fertility index (IFI), dissolved organic carbon (DOC), microbial biomass carbon (MBC), particulate organic carbon (POC), their effective rates, and soil carbon pool management index (CPMI) under different treatments were studied to clarify their relationships. The results showed that:① the application of amendments significantly increased soil pH and the contents of organic matter, alkali-hydrolyzed nitrogen, available phosphorus, and available potassium (P<0.05). The OM and JZ treatments had the most significant increase in soil comprehensive fertility index (P<0.05), with increases of 1.96 and 0.77 and 170.43% and 66.96%, respectively. ② Compared with those in the control treatment, the contents of POC, MBC, and DOC in JZ and OM increased by 110.30% and 84.81%, 61.08% and 46.56%, and 195.87% and 141.67%, respectively. The application of amendments significantly increased the soil carbon pool index (CPI) and CMPI (P<0.05), in which the OM treatment showed the most significant increase, with soil CPI and CMPI values increasing by 107.34% and 90.75% compared with those of the control, respectively. ③ Soil organic carbon and its labile fractions were positively correlated with IFI (P<0.05), and redundancy analysis showed that there were significant differences among different treatments. The interpretation rates of soil IFI, pH, and available potassium to organic carbon and its components reached significant levels, and the order of interpretation rates was IFI(74.6%)>pH (11.7%)>AK(6.5%). The application of vinasse biomass ash and organic fertilizer to acid purple soil had the most significant effect on improving soil fertility and soil quality and was conducive to promoting the accumulation and activation of soil carbon fractions.

[Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model].

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 µg·mL~(-1) of the absolute lethal concentration and 448 µg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.

Characteristics and therapeutic profile of TBI patients who underwent bilateral decompressive craniectomy: experience with 151 cases.

BACKGROUND: Decompressive craniectomy (DC) and intracranial pressure (ICP) monitoring are common approaches to reduce the death rate of Traumatic brain injury (TBI) patients, but the outcomes of these patients are unfavorable, particularly those who receive bilateral DC. The authors discuss their experience using ICP and other potential methods to improve the outcomes of TBI patients who receive bilateral DC. METHODS: Data from TBI patients receiving bilateral DC from Jan. 2008 to Jan. 2022 were collected via a retrospective chart review. Included patients who received unplanned contralateral DC after initial surgery were identified as unplanned secondary surgery (USS) patients. Patients' demographics and baseline medical status; pre-, intra-, and postoperative events; and follow-up visit outcome data were analyzed. RESULTS: A total of 151 TBI patients were included. Patients who underwent USS experienced more severe outcomes as assessed using the 3-month modified Rankin Scale score (P = 0.024). In bilateral DC TBI patients, USS were associated with worsen outcomes, moreover, ICP monitoring was able to lower their death rate and was associated with a lower USS incidence. In USS patients, ICP monitoring was not associated with improved outcomes but was able to lower their mortality rate (2/19, 10.5%, vs. 10/25, 40.0%; P = 0.042). CONCLUSION: The avoidance of USS may be associated with improved outcomes of TBI patients who underwent bilateral DC. ICP monitoring was a potential approach to lower USS rate in TBI patients, but its specific benefits were uncertain.

[Anti-tumor and analgesic activity evaluation and mechanism of Compound Kushen Injection].

This study aims to evaluate the anti-tumor and analgesic activities of Compound Kushen Injection(CKI) based on zebrafish model in vivo and investigate the anti-tumor mechanism. To be specific, zebrafish tumor xenotransplantation model was established by microinjection of murine LPC H12 cells into yolk sac. Then the high-dose CKI(H-CKI), medium-dose CKI(M-CKI), low-dose CKI(L-CKI) groups, and the model group were set. The anti-tumor activity of CKI was evaluated with the tumor area growth fold and integral absorbance(IA) growth fold 72 h after administration. The peripheral pain and central pain in zebrafish were respectively induced with acetic acid(AA) and phorbol myristate acetate(PMA). Zebralab ViewPoint system was employed to monitor behavioral trajectory of zebrafish, and movement times, movement time, movement distance, and movement velocity were used to evaluate the analgesic activity of CKI. Finally, real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was performed to detect the expression levels of apoptosis-related B lymphocyte tumor-2(Bcl-2) and phosphatidylinositol-3-kinase(PI3 K)/protein kinase B(Akt or PKB) pathway-related genes, for the verification of the anti-tumor mechanism. Compared with the model group, M-CKI and H-CKI significantly reduced the growth folds of tumor area and IA, relief the peripheral pain and central pain. The mechanism was that CKI can up-regulate the expression of cysteine aspartic acid specific protease-3(caspase-3, Casp3) and caspase-9(Casp9), down-regulate the expression of phosphoinositide 3-kinase(PI3 K) and Akt, and significantly reduce the expression of Bcl-2, hypoxia-inducible factor-1α(HIF-1α), and vascular endothelial growth factor(VEGF). In conclusion, CKI has significant inhibitory effect on tumor growth and pain, which is related to the PI3 K/Akt signaling pathway. The pathway mediates cell apoptosis, suppresses tumor growth, and alleviates tumor pain.

Structural characterization of lignin and lignin-carbohydrate complex (LCC) of sesame hull.

In the present study, lignin and lignin-carbohydrate complex (LCC) constituting the cell wall structure of sesame hulls were investigated to explore novel techniques of dehulling. Milled wood lignin (MWL), Björkman LCC, and acid-soluble LCC (LCC-AcOH) were extracted from sesame hulls and characterized by carbohydrate composition analysis, molecular weight analysis, UV-vis spectroscopy, FT-IR, thermal analysis, Py-GC/MS, 2D HSQC NMR, and 31P NMR. The results showed that rhamnose accounted for the largest proportion of the lignin and LCC fractions, followed by glucose. Björkman LCC had the largest molecular weight, MWL had the smallest molecular weight, and LCC-AcOH had the largest polydispersity index. The lignin of sesame hulls consisted of syringyl (S), guaiacyl (G), p-hydroxyphenyl (H), and caffeyl alcohol (C) units. The most abundant monomer was guaiacyl (G), followed by caffeyl alcohol (C). C-type lignin is a new type of lignin that is different from the three traditional lignin monomers. The major lignin-linked bonds in the MWL and LCC-AcOH were ß-O-4' and ß-ß', and ß-5' bonds were present in the Björkman LCC. The major LCC chemical bonds in the three fractions were PhGly. These findings will provide the factual basis for exploring different dehulling methods to enhance the quality of sesame products.

[Study on liver diseases with zebrafish as an important tool].

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.

Circulating neutrophil-to-lymphocyte ratio at admission predicts the long-term outcome in acute traumatic cervical spinal cord injury patients.

BACKGROUND: The prognostic value of Neutrophil-to-Lymphocyte Ratio (NLR) for the outcome of acute cervical traumatic spinal cord injury (tSCI) patients has rarely been studied by now throughout the world. METHODS: We performed a single-center retrospective cohort study to evaluate the prognostic value of NLR from peripheral whole blood count in patients with acute cervical tSCI. Patients within 6 h of acute cervical tSCI treated between Dec 2008 and May 2018 in Huashan Hospital of Fudan University were enrolled. Outcomes of patients with tSCI were assessed using American spinal injury association Impairment Scale (AIS). 6-month outcomes were dichotomized into poor outcome group (AIS A to C) and good outcome group (AIS D and E). Uni- and multivariate analyses were performed to assess the independent predictors of 6-month outcome. Two prediction models based on admission characteristics were built to evaluate the prognostic value of NLR. The discriminative ability of predictive models was evaluated using the area under the curve (AUC). RESULTS: A total of 377 patients were identified from our single center in China PR. Multivariate analysis showed that age, AIS grade at admission, NLR (p < 0.001) and coagulopathy (p = 0.003) were independent predictors of the 6-months outcome for acute cervical tSCI patients. The model combing NLR and standard variables (AUC = 0.944; 95% CI, 0.923-0.964) showed a more favorable prognostic value than that without NLR (AUC = 0.841; 95% CI, 0.798-0.885) in terms of 6-month outcome. CONCLUSIONS: NLR is firstly identified as an independent predictor of the 6-month outcome in acute cervical tSCI patients worldwide. The prognostic value of NLR is favorable, and a high NLR is associated with poor outcome in patients with acute cervical tSCI.

ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats.

OBJECTIVE: To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism. MATERIAL AND METHODS: The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 µl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated. RESULTS: IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662. CONCLUSIONS: This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression.

Intensive blood pressure control reduces the risk of progressive hemorrhage in patients with acute hypertensive intracerebral hemorrhage: A retrospective observational study.

OBJECTIVE: To investigate the impact of intensive blood pressure control on progressive intracerebral hemorrhage and outcome in patients with high blood pressure and intracerebral hemorrhage. PATIENTS AND METHODS: A retrospective study was conducted recruiting 659 patients with acute hemorrhagic stroke between Jan. 2012 and May 2018. Patients recruited before May 2015 were treated with a target systolic level of <180 mm Hg, while those recruited after May 2015 received intensive blood pressure control treatment with a target systolic level of <140 mm Hg within 1 h. Uni- and multi-variate analysis were conducted to illustrate the association between intensive blood pressure control and progressive intracerebral hemorrhage. Mortality, rates of operation, length of ICU stay, modified Rankin scores at 90 days, and the rate of serious adverse events were also compared between the two groups. RESULTS: A total of 351 and 308 patients with acute hypertensive intracerebral hemorrhage were recruited before and after May 2015, respectively. Progressive intracerebral hemorrhage was identified among 111 out of 659 patients. Patients who received intensive blood pressure control showed a statistically lower rate of hematoma enlarging (43 of 308, 13.9% vs. 74 of 351, 21.1%, p = 0.018). The rates of operation and modified Rankin scores at 90 days were statistically lower with intensive blood control, while the mortality, length of ICU stay and rate of serious adverse events were similar between the two groups. Intensive BP control is an independent factor in predicting hematoma growing, with a more favorable discrimination (AUC = 0.889; 95%CI, 0.859-0.917) than other two models (AUC = 0.821; 95%CI, 0.791-0.852; and AUC = 0.635; 95%CI, 0.588-0.682). CONCLUSION: Intensive blood pressure control reduce the risk of progressive intracerebral hemorrhage and improved functional outcomes in patients with acute hemorrhagic stroke.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Predicting the 6-Month Outcome of Patients with Traumatic Brain Injury: A Retrospective Study.

BACKGROUND: Peripheral white blood cells are regularly analyzed on admission for patients with traumatic brain injury (TBI). The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in predicting the 6-month outcome of patients with TBI is unclear. METHODS: We designed a single-center retrospective cohort study. Patients admitted to Fudan University Huashan Hospital within 6 hours after TBI were identified between December 2004 and December 2017. The primary outcome was 6-month Glasgow Outcome Scale score. Independent predictors of 6-month outcome were assessed using uni- and multivariate analyses. Three models based on admission characteristics were built to evaluate the prognostic value of the NLR in predicting the outcome of patients with TBI. The discriminative ability of predictive models was evaluated by the area under the curve (AUC). RESULTS: A total of 1291 patients with TBI were included. Multivariate analysis showed age, Glasgow Coma Scale scores at admission, subdural hematoma, intraparenchymal hemorrhage, traumatic subarachnoid hemorrhage, NLR (P < 0.001), and coagulopathy (P = 0.028) were independent predictors of 6-month outcome. The model combining the NLR and standard variables (AUC = 0.936; 95% confidence interval [CI], 0.923-0.949) was more favorable in predicting 6-month outcome of patients with TBI than the model without the NLR (AUC = 0.901; 95% CI, 0.883-0.919) and the model based only on the NLR (AUC = 0.827; 95% CI, 0.802-0.852). CONCLUSIONS: NLR is an independent prognostic factor of predicting 6-month outcome of patients with TBI. A high NLR in patients with TBI is associated with poor outcome. The prognostic value of the NLR in predicting 6-month outcome of patients with TBI is favorable.

Interaction of STAT3 and RelB modulates MMP-1 in colon cancer.

BACKGROUND: MMP-1 (Matrix metalloproteinase-1) promotes carcinogenesis and distant metastasis in different cancers. Regulation of MMP-1 could occur at multiple levels: epigenetically, post-transcriptionally, or post-translationally. An increasing body of evidence supports that the cytoplasmic transcription factor STAT3 (signal transducer and activator of transcription 3) is activated constitutively in a variety of cancers wherein it significantly affects the growth of tumors and also facilitates metastasis. In addition, STAT3 has been found to regulate nuclear activity pro-inflammatory transcriptional factor, NF-κB signaling, especially, the alternative one (RelB/p100) by directly interacting with them METHOD AND RESULTS: In this proof of concept study, we tested the hypothesis that STAT3 interacts with RelB to promote tumor invasion by positively regulating MMP-1 in colon cancer. We found that RelB and STAT3 were constitutively localized in the nucleus of colon cancer in surgically-resected specimens with use of Western blot analysis, which was further confirmed by immunofluorescence (IF) staining in colon carcinoma cell line HT29. We further observed that STAT3/RelB knockdown resulted in reduced MMP-1. Our results from chromatin immunoprecipitation studies further established that association between RelB and MMP-1 promoter decreased when STAT3 was depleted, and conversely, STAT3 association with MMP-1 decreased with the knockdown of RelB. CONCLUSION: These results suggest that STAT3 and ReB constitute a minimal activator complex for positive regulation of MMP-1 in colon cancer.

Prognostic value of coagulation tests for in-hospital mortality in patients with traumatic brain injury.

BACKGROUND: Coagulopathy is commonly observed after traumatic brain injury (TBI). However, it is not known whether using the standard independent predictors in conjunction with coagulation tests would improve their prognostic value. We determined the incidence of TBI-associated coagulopathy in patients with isolated TBI (iTBI), evaluated the prognostic value of coagulation tests for in-hospital mortality, and tested their predictive power for in-hospital mortality in patients with iTBI. METHODS: We conducted a retrospective, observational database study on 2319 consecutive patients with iTBI who attended the Huashan Hospital Department of the Neurosurgery Neurotrauma Center at Fudan University in China between December 2004 and June 2015. Two models based on the admission characteristics were developed: model A included predictors such as age, Glasgow Coma Scale (GCS) score, pupil reactivity, type of injury, and hemoglobin and glucose levels, while model B included the predictors from model A as well as coagulation test results. A total of 1643 patients enrolled between December 2004 and December 2011 were used to derive the prognostic models, and 676 patients enrolled between January 2012 and June 2015 were used to validate the models. RESULTS: Overall, 18.6% (n = 432) of the patients developed coagulopathy after iTBI. The prevalence of acute traumatic coagulopathy is associated with the severity of brain injury. The percentage of platelet count <100 × 109/L, international normalized ratio (INR) > 1.25, the prothrombin time (PT) > 14 s, activated partial thromboplastin time (APTT) > 36 s, D-dimer >5 mg/L and fibrinogen (FIB) < 1.5 g/L was also closely related to the severity of brain injury, significance being found among three groups. Age, pupillary reactivity, GCS score, epidural hematoma (EDH), and glucose levels were independent prognostic factors for in-hospital mortality in model A, whereas age, pupillary reactivity, GCS score, EDH, glucose levels, INR >1.25, and APTT >36 s exhibited strong prognostic effects in model B. Discrimination and calibration were good for the development group in both prediction models. However, the external validation test showed that calibration was better in model B than in model A for patients from the validation population (Hosmer-Lemeshow test, p = 0.152 vs. p = 0.046, respectively). CONCLUSIONS: Coagulation tests can improve the predictive power of the standard model for in-hospital mortality after TBI.

Effects of Deferoxamine Mesylate on Hematoma and Perihematoma Edema after Traumatic Intracerebral Hemorrhage.

Deferoxamine mesylate can cross the blood-brain barrier and reduce iron accumulation in nervous tissue; moreover, it has a variety of neuroprotective functions in addition to complexing with iron ions. Such iron chelators are expected to become a new treatment option for intracerebral hemorrhage. This study evaluated the effects of deferoxamine mesylate on hematoma and edema absorption after traumatic intracerebral hemorrhage (TICH), and it provides clinical evidence for TICH treatment with deferoxamine mesylate. Patients with isolated TICH, confirmed by head computed tomography, were enrolled prospectively from January 2013 to December 2016. Patients were divided non-randomly into an experimental or control group as decided by the attending neurosurgeon. Patients in the experimental group received intravenous deferoxamine mesylate (20 mg/kg daily) from the day of admission for 5 consecutive days. We evaluated the impact of deferoxamine mesylate on the change in edema volume and the absorption of hematoma volume using a propensity score-matched analysis. In total, 190 patients were included. After matching, 94 patients were included in the final analysis (47 per group); no variable differed significantly between the two groups. The hematoma volume on the 7th day in the control group was higher than that at the same time-point in the experimental group (9.4 ± 7.2 vs. 5.2 ± 4.8 mL; p = 0.001). There was no difference in hematoma volume on Day 1 (12.6 ± 7.8 vs. 12.8 ± 6.4 mL; p = 0.896), Day 3 (12.4 ± 7.4 vs. 11.4 ± 4.9 mL; p = 0.442), and Day 14 (3.2 ± 3.0 vs. 2.5 ± 2.6 mL; p = 0.215) between the groups. The absorption of hematoma volume between the 1st and 3rd days and the 1st and 7th days in the experimental group was higher than that during the same periods in the control group. The edema volumes on the 3rd, 7th, and 14th days in the control group were higher than those at the same time-points in the experimental group. There was no difference in edema volume on the 1st day. The changes in edema volume between the 1st and 3rd days, the 1st and 7th days, and the 1st and 14th days in the control group were higher than those during the same periods in the experimental group. Deferoxamine mesylate may accelerate hematoma absorption and inhibit edema after TICH; however, further investigation is required to reach definitive conclusions.

Coagulopathy in Traumatic Brain Injury and Its Correlation with Progressive Hemorrhagic Injury: A Systematic Review and Meta-Analysis.

The association between coagulopathy and either isolated traumatic brain injury (TBI) or progressive hemorrhagic injury (PHI) remains controversial. The aims of this study were to evaluate whether isolated TBI induces pronounced coagulopathy, in comparison with non-TBI or TBI in conjunction with other injuries (TBI + other injuries), and to examine whether there is any evidence of a relationship between coagulopathy and PHI in patients who have experienced TBI. The MEDLINE(®) and Embase databases, and the Cochrane Central Register of Controlled Trials (Central), were trawled for relevant studies. Searches covered the period from the inception of each of the databases to June 2015, and were conducted using appropriate combinations of terms and key words based on medical subject headings (MeSH). Studies were included if they compared isolated TBI with a similar severity of injury to other body regions, or compared PHI with non-PHI, with regard to coagulation tests and the prevalence of coagulopathy. We extracted the means and standard deviations (SD) of coagulation test levels, as well as their ranges or the percentage of abnormal coagulation tests, in both cases and controls. A total of 19 studies were included in our systematic review and meta-analysis. Only the mean fibrinogen (FIB) in isolated TBI was found to be significantly higher than in TBI + other injuries (pooled mean difference [MD] 32.09; 95% confidence interval [CI] 4.92-59.25; p = 0.02); in contrast, it was also significantly higher than in non-TBI (pooled MD 15.44; 95% CI 0.28-30.59; p = 0.05). We identified 15 studies that compared coagulopathy between a PHI group and a non-PHI group. The PHI group had a lower platelet count (PLT) value (pooled MD -19.21; 95% CI: -26.99 to -11.44, p < 0.001) and a higher international normalized ratio (INR) value (pooled MD 0.07; 95% CI: 0.02-0.13, p = 0.006) than the non-PHI group, but no differences were observed in the mean activated partial thromboplastin time (APTT) and prothrombin time (PT) between the PHI and non-PHI patients. In addition, PHI was significantly associated with a higher percentage of INR >1.2 (pooled OR 3.49 [95% CI 1.97-6.20], p < 0.001), PLT <100 × 109/L (pooled OR 4.74 [95% CI 2.44-9.20], p < 0.001), and coagulopathy (pooled OR 2.52; 95% CI 1.88- 3.38; p < 0.001), compared with non-PHI. The current clinical evidence does not indicate that the prevalence of coagulopathy in TBI is significantly higher than in injuries of similar severity to other areas of the body, or in multiple injuries with TBI. With respect to the association between coagulopathy and PHI, the occurrence of coagulopathy, INR, and PLT was significantly associated with PHI, but APTT and PT were not found to be associated with PHI. In the future, high quality research will be required to further characterize the effects of coagulopathy on TBI and subsequent PHI.

Low-dose recombinant factor VIIa for reversing coagulopathy in patients with isolated traumatic brain injury.

PURPOSE: The purpose of this study was to investigate the role of low-dose recombinant factor VIIa (rFVIIa) (20 µg/kg) in reversing coagulopathy in patients with isolated traumatic brain injury (TBI). MATERIALS AND METHODS: Patients with isolated TBI and coagulopathy at admission were enrolled prospectively from January 2010 to December 2011. The patients were divided into 2 groups: the rFVIIa and the no-rFVIIa groups. In the rFVIIa group, patients received a single dose of 20 µg/kg rFVIIa intravenously to reverse their coagulopathy in addition to blood products. Patients in the no-rFVIIa group received only blood products to correct the coagulopathy. The clinical outcome variables evaluated included changes in coagulation parameters after administration for reversing coagulopathy, the occurrence of progressive hemorrhagic injury (PHI), intensive care unit length of stay, the incidence of thromboembolic complications, inhospital mortality, and 90-day Glasgow Outcome Scale. RESULTS: Eighty-seven patients were ultimately included in this study. Of them, 49 patients were treated with blood products alone, whereas 38 patients also received rFVIIa to reverse their coagulopathy. The improvement in international normalized ratio was greater in the rFVIIa group (0.26 [0.18-0.39]) than in the no-rFVIIa group (0.06 [-0.11 to 0.30]) (P = .001). In addition, the improvement in lactate was also greater in the rFVIIa group (0.33 [-0.18 to 0.54]) than in the no-rFVIIa group (0.04 [-0.25 to 0.20]) (P = .029). During the period after we began to correct the coagulopathy, PHI occurred in 19 patients (38.8%) in the no-rFVIIa group, which was significantly higher than that in the rFVIIa group (7, 18.4%; P = .040). The rate of cerebral infarction was similar in both groups (10.2% vs 5.3%). There was a trend indicating that low-dose rFVIIa therapy was associated with a lower mortality, but the association was not statistically significant (P = .266). CONCLUSIONS: The use of low-dose rFVIIa (20 µg/kg) is effective for correcting coagulopathy in patients with TBI without an increase in thromboembolic events. Moreover, it is more effective for preventing the occurrence of PHI.

[The PTD domain of Tat protein enhance GFP protein delivering into myeloma cell SP2/0].

In order to detect the protein delivery mediated by the PTD (protein transduction domain) of TAT Protein, a expression vector, named pT7460-GFP, was constructed by insert the PTD DNA Sequence, followed by a GFP (green fluorescent protein) gene fused in-frame, into the pT7450 vector. The TAT-GFP fusion protein was expressed in the E. coli ER2566. Most of the fusion protein was presented in the inclusion body. The protein was purified by Ni2+ affinity chromatography under denature conditions, then by a Sepharose Q column to remove urea. The soluble denatured protein was added directly to medium containing the Myeloma Cell SP2/0. It came out that the fusion protein could be detected delivered into the cells under fluorescent microscope in a short time.