Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

Initial CT-based radiomics nomogram for predicting in-hospital mortality in patients with traumatic brain injury: a multicenter development and validation study.

OBJECTIVE: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI). METHODS: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated. RESULTS: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful. CONCLUSION: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function.

BACKGROUND: Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury (SA-AKI) than among patients with sepsis. However, the pathogenesis underlying SA-AKI remains unclear. We hypothesized that the source of infection affects development of SA-AKI. We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI. METHODS: Between January 2013 and January 2018, 113 patients with SA-AKI admitted to our Emergency Center were identified and divided into two groups: those with pulmonary infections and those with other sources of infection. For each patient, we collected data from admission until either discharge or death. We also recorded the clinical outcome after 90 days for the discharged patients. RESULTS: The most common source of infection was the lung (52/113 cases, 46%), followed by gastrointestinal (GI) (25/113 cases, 22.1%) and urinary (22/113, 19.5%) sources. Our analysis showed that patients with SA-AKI had a significantly worse outcome (30/52 cases, P<0.001) and poorer kidney recovery (P=0.015) with pulmonary sources of infection than those infected by another source. Data also showed that patients not infected by a pulmonary source more likely experienced shock (28/61 cases, P=0.037). CONCLUSION: This study demonstrated that the source of infection influenced the outcome of SA-AKI patients in an independent manner. Lung injury may influence renal function in an as-yet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection.

Safety awareness and use of child safety seats among parents after the legislation in Shanghai.

PURPOSE: To investigate the changes and underlying mechanisms in parents' safety awareness and the use of child safety seats after the mandatory legislation in Shanghai city, China. METHODS: This study was carried out by Shanghai Key Laboratory of Environment and Children's Health using a multi-stage, simple random sampling method. Volunteers with children aged 0-12 months were recruited. Child safety seats were sent to each volunteer's family. Telephone encounters and/or on-site visits were used to collect data from parents using a phased survey on children's safety during car use. RESULTS: Among all respondents, 91.2% had heard of motor vehicle accidents involving children, and 97.2% could describe the appropriate use of a safety seat to minimize the risk of child injury in a collision. Among 1078 families with newborns, awareness of child safety seats was 91.9%. There were 86% patients aware that new laws and regulations have been released regarding the use of child safety seats, and 98.5% of them plan to comply with the new laws. Moreover, 61% patients think that taxis should be routinely equipped with child safety seats. CONCLUSION: The parents in Shanghai obtained a high level of awareness of children's traffic safety after the introduction of child safety seats legislation, and had a positive experience related to the use of child safety seats. Taxi may be an important area of focus for implementation of child traffic safety. Traffic safety laws and regulations with further impact should be continuously studied.

Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia.

Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. Autophagy plays an important role in neuronal apoptosis induced by ischemia. However, whether autophagy is involved in neuron apoptosis induced by cardiac arrest has been less studied. This study found that TRPML1 participates in cerebral ischemic reperfusion injury. Primary neurons were isolated and treated with mucolipin synthetic agonist 1 (ML-SA1), as well as infected with the recombinant lentivirus TRPML1 overexpression vector in vitro. ML-SA1 was delivered intracerebroventricularly in transient global ischemia model. Protein expression levels were determined by western blot. Neurological deficit score and the infarct volume were analyzed for the detection of neuronal damage. We found that TRPML1 was significantly downregulated in vivo and in vitro ischemic reperfusion model. We also observed that TRPML1 overexpression or treatment with the ML-SA1 attenuated neuronal death in primary neurons and ameliorated neurological dysfunction in vivo. Our findings suggested that autophagy and apoptosis were activated after transient global ischemia. Administration of ML-SA1 before transient global ischemia ameliorated neurological dysfunction possibly through the promotion of autophagy and the inhibition of apoptosis.

Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro.

Isoquercetin has exhibited a wide range of therapeutic properties, including antioxidant, anti-inflammatory and anti-allergic activities. The aim of the present study was to investigate the effect of isoquercetin on rats with 2 h middle cerebral artery occlusion (MCAO) and evaluate the neuroprotective effect of isoquercetin on a primary culture of rat hippocampal neuronal cells subjected to oxygen-glucose deprivation followed by reoxygenation (OGD/R). In vivo, the rats treated with isoquercetin exhibited a lower degree of neurological dysfunction and smaller infarct volume than the vehicle-treated rats. In vitro, it was found that isoquercetin prevented the OGD/R-induced increase in apoptosis, lactate dehydrogenase release and reduction in cell viability. Additionally, isoquercetin induced the upregulation of nuclear factor erythroid 2-related factor 2 gene and protein expression, and increased extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation. This indicates that the ERK1/2 pathway may contribute to the neuroprotective effect of isoquercetin against OGD/R-induced oxidative damage in rat hippocampal neurons. These findings suggest the potential importance of isoquercetin in the treatment of ischemia/reperfusion-related brain injury and associated diseases.

Differentially expressed miRNAs in sepsis-induced acute kidney injury target oxidative stress and mitochondrial dysfunction pathways.

OBJECTIVE: To identify specific miRNAs involved in sepsis-induced AKI and to explore their targeting pathways. METHODS: The expression profiles of miRNAs in serum from patients with sepsis-induced AKI (n = 6), sepsis-non AKI (n = 6), and healthy volunteers (n = 3) were investigated by microarray assay and validated by quantitative PCR (qPCR). The targets of the differentially expressed miRNAs were predicted by Target Scan, mirbase and Miranda. Then the significant functions and involvement in signaling pathways of gene ontology (GO) and KEGG pathways were analyzed. Furthermore, eight miRNAs were randomly selected out of the differentially expressed miRNAs for further testing by qPCR. RESULTS: qPCR analysis confirmed that the expressions levels of hsa-miR-23a-3p, hsa-miR-4456, hsa-miR-142-5p, hsa-miR-22-3p and hsa-miR-191-5p were significantly lower in patients with sepsis compared with the healthy volunteers, while hsa-miR-4270, hsa-miR-4321, hsa-miR-3165 were higher in the sepsis patients. Statistically, miR-4321; miR-4270 were significantly upregulated in the sepsis-induced AKI compared with sepsis-non AKI, while only miR-4321 significantly overexpressed in the sepsis groups compared with control groups. GO analysis showed that biological processes regulated by the predicted target genes included diverse terms. They were related to kidney development, regulation of nitrogen compound metabolic process, regulation of cellular metabolic process, cellular response to oxidative stress, mitochondrial outer membrane permeabilization, etc. Pathway analysis showed that several significant pathways of the predicted target genes related to oxidative stress. miR-4321 was involved in regulating AKT1, mTOR and NOX5 expression while miR-4270 was involved in regulating PPARGC1A, AKT3, NOX5, PIK3C3, WNT1 expression. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in oxidative stress and mitochondrial dysfunction. CONCLUSION: This study might help to improve understanding of the relationship between serum miRNAs and sepsis-induced AKI, and laid an important foundation for further identification of the potential mechanisms of sepsis-induced AKI and oxidative stress and mitochondrial dysfunction.

Mechanical thrombectomy by Solitaire stent for treating acute ischemic stroke: A prospective cohort study.

BACKGROUND: Acute ischemic stroke (AIS) is a worldwide serious health problem. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the standard treatment; however, only a small number of patients benefit from it due to the strict application restrictions. Recently, more and more evidence prove mechanical thrombectomy is an effective and safe therapy of AIS. PATIENTS AND METHODS: From December 2010 to March 2015, 83 patients who underwent mechanical thrombectomy were collected as a sample pool. All patients met the following criteria: National Institutes of Health Stroke Scale (NIHSS) score ≥10, treatment performed within 6 h from the onset of symptoms, no large hypodensity on CT or multimodal MRI, and angiography revealed occlusion of a major cerebral artery. Recanalization rates were assessed immediately post-procedure by follow-up angiography according to the thrombolysis in cerebral infarction score criteria. Assessment of the modified Rankin Scale was performed 90 days after treatment. RESULTS: The mean age of patients was 63.3 years, and NIHSS scores 19.12 ± 4.60 at presentation. The vessel occlusions occurred in the middle cerebral artery (68.7%), distal internal carotid artery (7.2%), internal carotid artery with tandem middle cerebral artery occlusion (14.5%), basilar artery (2.4%), and vertebral artery (7.2%). Successful recanalization (TICI 3/2b) was achieved in 56 of 83 patients (67.5%). At 90-day follow-up, good clinical outcome (mRS ≤ 2) was achieved in 33 of 83 patients (39.8%), while 20 patients died (24.1%). CONCLUSIONS: This study revealed mechanical thrombectomy with Solitaire stent device was an effective and safe therapy, which achieved a high rate of angiographic recanalization and independent outcome accompanied by a low mortality rate.

Expression of HMGB1 in septic serum induces vascular endothelial hyperpermeability.

The aim of the present study was to investigate the effects of high mobility group protein B1 (HMGB1), which is expressed in the serum of patients with sepsis, on vascular endothelial permeability. Sera from patients with sepsis were used to treat endothelial cells (ECs), and the effect on endothelial permeability was evaluated using immunofluorescence. The morphologies of endothelial cytoskeletal actin and vascular endothelial (VE)­cadherin were assessed using laser scanning confocal microscopy. The protein expression levels of HMGB1, B­cell lymphoma 2 (BCL­2) and BCL­2­associated X protein (BAX) were detected using western blotting. EC apoptosis was measured using flow cytometry. The results demonstrated that HMGB1 was significantly expressed in the serum 24 h following the onset of sepsis, and the expression levels peaked at 48 h, which were sustained until 96 h post­onset. Compared with the control group, treatment of the ECs with 20% septic serum in vitro significantly increased endothelial monolayer permeability (P<0.01), markedly induced transcellular filamentous (F)­actin rearrangement with stress fiber formation, and resulted in the localization of VE­cadherin fragmentations at the cell borders with increased gaps between ECs. Furthermore, flow cytometry showed that the apoptotic rate of ECs was significantly increased following treatment with septic serum. In addition, the expression levels of BAX were significantly increased, whereas the expression levels of BCL­2 were significantly decreased. Pretreatment with an HMGBI inhibitor (ethyl pyruvate; 5 µM) 24 h prior to treatment with the septic serum attenuated the effects of septic serum treatment. Together, these findings suggested that treatment of ECs with sera from patients with sepsis may induce the loss of vascular endothelial monolayer integrity, elicit the formation of endothelial F­actin stress fibers and initiate VE­cadherin redistribution, which may be attributed to high levels of HMGB1 in the serum. This mechanism also appears to involve changes in the activation of BAX and BCL­2, resulting in EC apoptosis.

Comparison of Therapeutic Effect of Recombinant Tissue Plasminogen Activator by Treatment Time after Onset of Acute Ischemic Stroke.

We aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) administered at different time windows within the first 6 hours after onset of acute ischemic stroke (AIS). A retrospective analysis was performed of data collected from 194 patients who received rt-PA thrombolysis within 4.5 hours after AIS onset and from 29 patients who received rt-PA thrombolysis between 4.5-6 hours after AIS onset. The National Institutes of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P < 0.05) at 24 hours and 7 days after onset. There was no statistical difference in the modified Rankin score or mortality at day 90 after treatment between the two groups (P > 0.05). In conclusion, AIS patients who received rt-PA treatment between 4.5-6 hours after onset were similar in therapeutic efficacy to those who received rt-PA within 4.5 hours after onset. Our results suggest that intravenous thrombolytic therapy for AIS within 4.5-6 hours after onset is effective and safe.

Bayesian estimation on diagnostic performance of Face, Legs, Activity, Cry, and Consolability and Neonatal Infant Pain Scale for infant pain assessment in the absence of a gold standard.

BACKGROUND: Nonverbal pediatric patients such as infants are unable to describe their pain, which leads to the lack of a gold standard scale for their pain assessment. The aim of this study was to estimate the diagnostic performance of Face, Legs, Activity, Cry, and Consolability (FLACC) scale and Neonatal Infant Pain Scale (NIPS) for infants' pain in the absence of a gold standard. METHODS: This prospective observational study recruited 202 postoperative infants, aged <12 months. Postoperative pain intensity was evaluated using FLACC and NIPS scales. The diagnostic performance of these two scales was to estimate using a Bayesian latent class model with conditional dependence. McNemar's test was applied to test whether NIPS and FLACC tests differ from each other. RESULTS: Under a combined model with conditional dependence, the median posterior sensitivity and specificity of the FLACC were 89.94% (95% CI: 78.48-96.83%) and 87.82% (95% CI: 78.6-95.23%), respectively. The sensitivity and specificity of the NIPS were 85.94% (95% CI: 72.15-95.6%) and 92.61% (84.05-97.52%), respectively. McNemar's test demonstrated no significant difference between FLACC and NIPS in either sensitivity or specificity. CONCLUSION: Both the FLACC and NIPS have excellent sensitivity and specificity for pain assessment in infants. The comparison test showed that the FLACC scale was no different to the NIPS scale in sensitivity and specificity.

Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients.

BACKGROUND: Sedation reduces patient levels of anxiety and stress, facilitates the delivery of care and ensures safety. Alpha-2 agonists have a range of effects including sedation, analgesia and antianxiety. They sedate, but allow staff to interact with patients and do not suppress respiration. They are attractive alternatives for long-term sedation during mechanical ventilation in critically ill patients. OBJECTIVES: To assess the safety and efficacy of alpha-2 agonists for sedation of more than 24 hours, compared with traditional sedatives, in mechanically-ventilated critically ill patients. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 10, 2014), MEDLINE (1946 to 9 October 2014), EMBASE (1980 to 9 October 2014), CINAHL (1982 to 9 October 2014), Latin American and Caribbean Health Sciences Literature (1982 to 9 October 2014), ISI Web of Science (1987 to 9 October 2014), Chinese Biological Medical Database (1978 to 9 October 2014) and China National Knowledge Infrastructure (1979 to 9 October 2014), the World Health Organization international clinical trials registry platform (to 9 October 2014), Current Controlled Trials metaRegister of controlled trials active registers (to 9 October 2014), the ClinicalTrials.gov database (to 9 October 2014), the conference proceedings citation index (to 9 October 2014) and the reference lists of included studies and previously published meta-analyses and systematic reviews for relevant studies. We imposed no language restriction. SELECTION CRITERIA: We included all randomized and quasi-randomized controlled trials comparing alpha-2 agonists (clonidine or dexmedetomidine) versus alternative sedatives for long-term sedation (more than 24 hours) during mechanical ventilation in critically ill patients. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data. We contacted study authors for additional information. We performed meta-analyses when more than three studies were included, and selected a random-effects model due to expected clinical heterogeneity. We calculated the geometric mean difference for continuous outcomes and the risk ratio for dichotomous outcomes. We described the effects by values and 95% confidence intervals (CIs). We considered two-sided P < 0.05 to be statistically significant. MAIN RESULTS: Seven studies, covering 1624 participants, met the inclusion criteria. All included studies investigated adults and compared dexmedetomidine with traditional sedatives, including propofol, midazolam and lorazepam. Compared with traditional sedatives, dexmedetomidine reduced the geometric mean duration of mechanical ventilation by 22% (95% CI 10% to 33%; four studies, 1120 participants, low quality evidence), and consequently the length of stay in the intensive care unit (ICU) by 14% (95% CI 1% to 24%; five studies, 1223 participants, very low quality evidence). There was no evidence that dexmedetomidine decreased the risk of delirium (RR 0.85; 95% CI 0.63 to 1.14; seven studies, 1624 participants, very low quality evidence) as results were consistent with both no effect and appreciable benefit. Only one study assessed the risk of coma, but lacked methodological reliability (RR 0.69; 95% CI 0.55 to 0.86, very low quality evidence). Of all the adverse events included, the most commonly reported one was bradycardia, and we observed a doubled (111%) increase in the incidence of bradycardia (RR 2.11; 95% CI 1.39 to 3.20; six studies, 1587 participants, very low quality evidence). Our meta-analysis provided no evidence that dexmedetomidine had any impact on mortality (RR 0.99; 95% CI 0.79 to 1.24; six studies, 1584 participants, very low quality evidence). We observed high levels of heterogeneity in risk of delirium (I² = 70%), but due to the limited number of studies we were unable to determine the source of heterogeneity through subgroup analyses or meta-regression. We judged six of the seven studies to be at high risk of bias. AUTHORS' CONCLUSIONS: In this review, we found no eligible studies for children or for clonidine. Compared with traditional sedatives, long-term sedation using dexmedetomidine in critically ill adults reduced the duration of mechanical ventilation and ICU length of stay. There was no evidence for a beneficial effect on risk of delirium and the heterogeneity was high. The evidence for risk of coma was inadequate. The most common adverse event was bradycardia. No evidence indicated that dexmedetomidine changed mortality. The general quality of evidence ranged from very low to low, due to high risks of bias, serious inconsistency and imprecision, and strongly suspected publication bias. Future studies could pay more attention to children and to using clonidine

Serum uric acid is neuroprotective in Chinese patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator.

BACKGROUND: Exogenous uric acid (UA) is a neuroprotective antioxidant that reinforces the benefits of intravenous recombinant tissue plasminogen activator thrombolysis in animal thromboembolic stroke. However, whether serum uric acid (SUA) also increases the benefits of thrombolysis in Chinese patients with acute ischemic stroke (AIS) has yet to be fully defined. METHODS: A total of 216 consecutive AIS patients of Chinese origin treated with intravenous thrombolysis were enrolled in a prospective stroke registry. Demographic and clinical characteristics, conventional risk factors, important laboratory data, and neurologic course were prospectively recorded. Functional outcomes were assessed with the modified Rankin Scale (mRS) score on day 90 by telephone calls. Receiver operating characteristic curves and binary logistic regression models were used to examine the performance of SUA in predicting excellent outcomes (mRS, 0-1). RESULTS: SUA levels were significantly higher in patients with excellent outcomes than those in patients with poor outcomes (331.46 ± 103.39 versus 277.69 ± 105.62, P = .008). SUA had a modest power for predicting excellent outcomes as suggested by area under the curve of .665 ± .052, P = .003. In multivariate models, increased SUA levels (adjusted odds ratio, 1.005; 95% confidence interval, 1.002-1.009; P = .033) were associated with excellent outcomes independently of the effect of possible confounders. Spearman correlation tests indicated that there was an inverse correlation between SUA levels and stroke severity. CONCLUSIONS: Increased SUA levels are associated with excellent outcomes in Chinese patients with AIS treated with intravenous thrombolysis, giving additional support to administration of exogenous UA as an adjuvant to thrombolysis.

A simple Chinese risk score model for screening cardiovascular autonomic neuropathy.

BACKGROUND: The purpose of the present study was to develop and evaluate a risk score to predict people at high risk of cardiovascular autonomic dysfunction neuropathy (CAN) in Chinese population. METHODS AND MATERIALS: A population-based sample of 2,092 individuals aged 30-80 years, without previously diagnosed CAN, was surveyed between 2011 and 2012. All participants underwent short-term HRV test. The risk score was derived from an exploratory set. The risk score was developed by stepwise backward multiple logistic regression. The coefficients from this model were transformed into components of a CAN score. This score was tested in a validation and entire sample. RESULTS: The final risk score included age, body mass index, hypertension, resting hear rate, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed CAN. The area under the receiver operating curve was 0.726 (95% CI 0.686-0.766) for exploratory set, 0.784 (95% CI 0.749-0.818) for validation set, and 0.756 (95% CI 0.729-0.782) for entire sample. In validation set, at optimal cutoff score of 5 of 10, the risk score system has the sensitivity, specificity, and percentage that needed subsequent testing were 69, 78, and 30%, respectively. CONCLUSION: We developed a CAN risk score system based on a set of variables not requiring laboratory tests. The score system is simple fast, inexpensive, noninvasive, and reliable tool that can be applied to early intervention to delay or prevent the disease in China.

Salvianolate inhibits reactive oxygen species production in H(2)O(2)-treated mouse cardiomyocytes in vitro via the TGFß pathway.

AIM: To investigate the effects of salvianolate, a water-soluble active compound from Salvia miltiorrhiza Bunge, on reactive oxygen species (ROS) production in mouse cardiomyocytes in vitro. METHODS: Primary ventricular cardiomyocytes were prepared from neonatal mouse. The cell viability was determined using MTT assay. Culture medium for each treatment was collected for measuring the levels of NO, iNOS, total antioxidant capacity (TAOC) and transforming growth factor ß1 (TGFß1). TGFß1 and Smad2/3 expression in the cells was detected with Western blotting. RESULTS: H2O2 (1.25 mmol/L) did not significantly affect the cell viability, whereas the high concentration of salvianolate (5 g/L) alone dramatically suppressed the cell viability. Treatment of the cells with H2O2 (1.25 mmol/L) markedly increased ROS and iNOS production, and decreased the levels of NO, TAOC and TGFß1 in the culture medium. Furthermore, the H2O2 treatment significantly increased TGFß1 and Smad2/3 expression in the cells. Addition of salvianolate (0.05, 0.1, and 0.5 g/L) concentration-dependently reversed the H2O2-induced alterations in the culture medium; addition of salvianolate (0.05 g/L) reversed the H2O2-induced increases of TGFß1 and Smad2/3 expression in the cells. Blockage of TGFß1 with its antibody (1 mg/L) abolished the above mentioned effects of salvianolate. CONCLUSION: Salvianolate inhibits ROS and iNOS production and increases TAOC and NO levels in H2O2-treated cardiomyocytes in vitro via downregulation of Smad2/3 and TGFß1 expression. High concentration of salvianolate causes cytotoxicity in mouse cardiomyocytes.

Therapeutic effect of recombinant tissue plasminogen activator on acute cerebral infarction at different times.

BACKGROUND: The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) on the onset of acute cerebral infarction (ACI) at different time points of the first 6 hours. METHODS: A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI. RESULTS: National Institute of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P>0.05) at 24 hours and 7 days after ACI. There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups (P>0.05). CONCLUSIONS: The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rt-PA within 4.5 hours after the onset of this disease. Therefore, intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.

Efficacy and safety of a modified intravenous recombinant tissue plasminogen activator regimen in Chinese patients with acute ischemic stroke.

BACKGROUND: Thrombolytic treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA; 0.90 mg/kg, with a maximum dose of 90 mg) has been recommended as the standard management for acute ischemic stroke (AIS) thrombolysis. However, the dose of IV rtPA in Asia remains controversial. METHODS: This study was designed to verify the safety and efficacy of IV rtPA treatment for AIS with a lower dosage (0.90 mg/kg, with a maximum dose of 50 mg). Patients were divided into 3 dosage groups according to body weight (BW): group 1, <55 kg for 0.90 mg/kg; group 2, 55 to 67 kg for 0.75 to 0.90 mg/kg; and group 3, >67 kg for <0.75 mg/kg. The following data were collected: patient demographics, vascular risk factors, neuroimaging results, time of rtPA administration, National Institutes of Health Stroke Scale score before treatment and at 24 hours, and a modified Rankin Scale (mRS) score at 3 months. RESULTS: Eighty-three AIS patients who were of Han Chinese descent were included in the study. The baseline characteristics of the 3 dosage groups were well matched. In group 1 (BW <55 kg for 0.90 mg/kg; n = 19), 57.1% had a favorable outcome at 3 months, compared with 61.2% of patients in group 2 (BW 55-67 kg for 0.75-0.90 mg/kg; n = 33) and 51.5% in group 3 (BW >67 kg for <0.75 mg/kg; n = 31; P = .362). There were no significantly statistical differences in the incidence of symptomatic intracerebral hemorrhage and mortality rate. CONCLUSIONS: This IV rtPA regimen (0.90 mg/kg, with a maximum dose of 50 mg) not only shows sufficient favorable outcome in clinical practice in Chinese patients with AIS but also good health economic savings. This regimen could be suitable for many developing countries.

[Study of automated acid-base mapping on diagnose and treatment of community acquired pneumonia in emergency department].

OBJECTIVE: To analyze the value of automated acid-base mapping on diagnose and treatment of patients with community acquired pneumonia (CAP) in emergency department. METHODS: According to medical history, pulmonary function test, diagnosing guideline of chronic obstructive pulmonary disease (COPD), 111 patients with CAP were divided into two groups: single CAP group (n=56) and COPD complicated with CAP group [acute exacerbation of chronic obstructive pulmonary disease (AECOPD) group, n=55]. After enquiring medical history, arterial blood samples were drawn for blood gas analysis and automated acid-base mapping was analyzed. RESULTS: Arterial blood gas analysis showed arterial carbon dioxide partial pressure (PaCO(2)), HCO(3)(-), base excess of AECOPD group were obviously higher than those in CAP group (PaCO(2): 7.714±2.414 kPa vs. 5.896±1.308 kPa, HCO(3)(-): 30.767±7.185 mmol/L vs. 25.014±3.043 mmol/L, BE: 4.345±5.371 mmol/L vs. -0.354±3.180 mmol/L, all P<0.01). Automated acid-base mapping showed acid-base disturbance of AECOPD group was 89.1% and CAP group was 66.1%. Chi-square analysis were done for patients of normal (10.9%, 33.9%), acute respiratory acidosis (12.7%, 14.3%), chronic respiratory acidosis (49.1%, 10.7%), respiratory alkalosis (7.3%, 14.3%), metabolic acidosis (12.7%, 17.9%), metabolic alkalosis (12.7%, 8.9%) between AECOPD group and CAP group, and statistical significance was found between AECOPD group and single CAP group (χ (2)=24.421, P=0.001). Advanced Chi-square analysis for patients of normal, acute respiratory acidosis, respiratory alkalosis, metabolic acidosis, metabolic alkalosis were done and showed no statistical difference (χ (2)=5.280, P=0.260). It is indicated chronic respiratory acidosis occurrences rate in AECOPD patients was higher than single CAP patients. CONCLUSIONS: Our study demonstrated that automated acid-base mapping may be helpful for emergency physician to rapidly recognize multi-acid-base disturbance in patients with CAP, and to promptly identify acute or chronic phase of respiratory disease.

Anti-CHMP5 single chain variable fragment antibody retrovirus infection induces programmed cell death of AML leukemic cells in vitro.

AIM: Over-expressed CHMP5 was found to act as oncogene that probably participated in leukemogenesis. In this study, we constructed the CHMP5 single chain variable fragment antibody (CHMP5-scFv) retrovirus and studied the changes of programmed cell death (PCD) of AML leukemic cells after infection by the retrovirus. METHODS: The anti-CHMP5 KC14 hybridoma cell line was constructed to generate monoclonal antibody of CHMP5. The protein expression of CHMP5 was studied using immunofluorescence analysis. pMIG-CHMP5 scFv antibody expressible retroviral vector was constructed to prepare CHMP5-scFv retrovirus. AML leukemic U937 cells were infected with the retrovirus, and programmed cell death was studied using confocal microscope, FCM and Western blot. RESULTS: We obtained a monoclonal antibody of CHMP5, and found the expression of CHMP5 was up-regulated in the leukemic cells. After U937 cells were infected with CHMP5-scFv retrovirus, CHMP5 protein was neutralized. Moreover, the infection resulted in a significant increase in apoptosis and necrosis of U937 cells. In U937 cells infected with CHMP5-scFv retrovirus, apoptosis-inducing factor (AIF)-mediated caspase-independent necrotic PCD was activated, but autophagic programmed cell death was not observed. Neither the intrinsic nor extrinsic apoptotic PCD pathway was activated. The granzyme B/perforin-mediated caspase-dependent apoptotic PCD pathway was not activated. CONCLUSION: CHMP5-scFv retrovirus can neutralize the abnormally high levels of the CHMP5 protein in the cytosol of AML leukemic U937 cells, thereby inducing the programmed cell death of the leukemic cells via AIF-mediated caspase-independent necrosis and apoptosis.

Central venous access sites for the prevention of venous thrombosis, stenosis and infection.

BACKGROUND: Central venous access (CVA) is widely used. However, its thrombotic, stenotic and infectious complications can be life-threatening and involve high-cost therapy. Research revealed that the risk of catheter-related complications varied according to the site of CVA. It would be helpful to find the preferred site of insertion to minimize the risk of catheter-related complications. This review was originally published in 2007 and was updated in 2011. OBJECTIVES: 1. Our primary objective was to establish whether the jugular, subclavian or femoral CVA routes resulted in a lower incidence of venous thrombosis, venous stenosis or infections related to CVA devices in adult patients.2. Our secondary objective was to assess whether the jugular, subclavian or femoral CVA routes influenced the incidence of catheter-related mechanical complications in adult patients; and the reasons why patients left the studies early. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2011, Issue 9), MEDLINE, CINAHL, EMBASE (from inception to September 2011), four Chinese databases (CBM, WANFANG DATA, CAJD, VIP Database) (from inception to November 2011), Google Scholar and bibliographies of published reviews. The original search was performed in December 2006. We also contacted researchers in the field. There were no language restrictions. SELECTION CRITERIA: We included randomized controlled trials comparing central venous catheter insertion routes. DATA COLLECTION AND ANALYSIS: Three authors assessed potentially relevant studies independently. We resolved disagreements by discussion. Dichotomous data on catheter-related complications were analysed. We calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. MAIN RESULTS: We identified 5854 citations from the initial search strategy; 28 references were then identified as potentially relevant. Of these, we Included four studies with data from 1513 participants. We undertook a priori subgroup analysis according to the duration of catheterization, short-term (< one month) and long-term (> one month) defined according to the Food and Drug Administration (FDA).No randomized controlled trial (RCT) was found comparing all three CVA routes and reporting the complications of venous stenosis.Regarding internal jugular versus subclavian CVA routes, the evidence was moderate and applicable for long-term catheterization in cancer patients. Subclavian and internal jugular CVA routes had similar risks for catheter-related complications. Regarding femoral versus subclavian CVA routes, the evidence was high and applicable for short-term catheterization in critically ill patients. Subclavian CVA routes were preferable to femoral CVA routes in short-term catheterization because femoral CVA routes were associated with higher risks of catheter colonization (14.18% or 19/134 versus 2.21% or 3/136) (n = 270, one RCT, RR 6.43, 95% CI 1.95 to 21.21) and thrombotic complications (21.55% or 25/116 versus 1.87% or 2/107) (n = 223, one RCT, RR 11.53, 95% CI 2.80 to 47.52) than with subclavian CVA routes. Regarding femoral versus internal jugular routes, the evidence was moderate and applicable for short-term haemodialysis catheterization in critically ill patients. No significant differences were found between femoral and internal jugular CVA routes in catheter colonization, catheter-related bloodstream infection (CRBSI) and thrombotic complications, but fewer mechanical complications occurred in femoral CVA routes (4.86% or 18/370 versus 9.56% or 35/366) (n = 736, one RCT, RR 0.51, 95% CI 0.29 to 0.88). AUTHORS' CONCLUSIONS: Subclavian and internal jugular CVA routes have similar risks for catheter-related complications in long-term catheterization in cancer patients. Subclavian CVA is preferable to femoral CVA in short-term catheterization because of lower risks of catheter colonization and thrombotic complications. In short-term haemodialysis catheterization, femoral and internal jugular CVA routes have similar risks for catheter-related complications except internal jugular CVA routes are associated with higher risks of mechanical complications.