fosA11, a novel chromosomal-encoded fosfomycin resistance gene identified in Providencia rettgeri.

This study investigated resistance genes corresponding to the fosfomycin resistance phenotype in clinical isolate Providencia rettgeri W986, as well as characterizing the enzymatic activity of FosA11 and the genetic environment. Antimicrobial susceptibility testing was performed using the agar microdilution method based on the Clinical and Laboratory Standards Institute guidelines. The whole genomic sequence of Providencia rettgeri W986 was obtained using Illumina sequencing and the PacBio platform. The fosA-11 gene was amplified by PCR and cloned into the pUCP20 vector. The recombinant strain pCold1-fosA11-BL21 was expressed to extract the target protein, and absorbance photometry was applied for enzymatic parameter determination. Minimal inhibitory concentration (MIC) tests showed that W986 conferred fosfomycin resistance and was inhibited by phosphonoformate, thereby indicating the presence of a FosA protein. A novel resistance gene designated as fosA11 was identified by whole-genome sequencing and bioinformatics analysis, and it shared 54.41%-64.23% amino acid identity with known FosA proteins. Cloning fosA11 into Escherichia coli obtained a significant increase (32-fold) in the MIC with fosfomycin. Determination of the enzyme kinetics showed that FosA11 had a high catalytic effect on fosfomycin, with Km = 18 ± 4 and Kcat = 56.1 ± 3.2. We also found that fosA11 was located on the chromosome, but the difference in the GC content between the chromosome and fosA11 was dubious, and thus further investigation is required. In this study, we identified and characterized a novel fosfomycin inactivation enzyme called FosA11. The origin and prevalence of the fosA11 gene in other bacteria require further investigation.IMPORTANCEFosfomycin is an effective antimicrobial agent against Enterobacterales strains. However, the resistance rate of fosfomycin is increasing year by year. Therefore, it is necessary to study the deep molecular mechanism of bacterial resistance to fosfomycin. We identified a novel chromosomal fosfomycin glutathione S-transferase, FosA11 from Providencia rettgeri, which shares a very low identity (54.41%-64.23%) with the previously known FosA and exhibits highly efficient catalytic ability against fosfomycin. Analysis of the genetic context and origin of fosA11 displays that the gene and its surrounding environments are widely conserved in Providencia and no mobile elements are discovered, implying that FosA11 may be broadly important in the natural resistance to fosfomycin of Providencia species.

A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage.

BACKGROUND: A20 may be a neuroprotective factor. Herein, we aimed to investigate whether serum A20 levels were associated with disease severity, delayed cerebral ischemia (DCI), and outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this prospective cohort study containing 112 aSAH patients and 112 controls, serum A20 levels were quantified. At 90 d poststroke, Modified Rankin Scale (MRS) scores ≥3 were defined as a poor outcome. All correlations and associations were assessed using multivariate analysis. RESULTS: Compared with controls, there was a significant elevation of serum A20 levels in patients (median 123.7 pg/mL vs. 25.8 pg/mL; P<0.001). Serum A20 levels were independently correlated with Hunt-Hess scores (ß 9.854; 95% confidence interval [95% CI] 2.481-17.227, P=0.009) and modified Fisher scores (ß 10.349, 95% CI 1.273-19.424, P=0.026). Independent associations were found between serum A20 levels and poor outcome (odds ratio [OR] 1.015, 95% CI 1.000-1.031, P=0.047) and DCI (OR 1.018, 95% CI 1.001-1.035, P=0.042). Areas under the curve for predicting poor outcome and DCI were 0.771 (95% CI 0.682-0.845) and 0.777 (95% CI 0.688-0.850), respectively. Serum A20 levels ≥128.15 pg/mL predicted poor outcome, with a sensitivity of 73.9% and specificity of 74.2%, and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with 65.5% sensitivity and 89.2% specificity. Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores (both P>0.05). CONCLUSION: Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH, implying that serum A20 may be a potential prognostic biomarker for aSAH.

Association between calf circumference and cardiac metabolic risk factors in middle-aged and elderly women.

Aims: To assess the correlation between calf circumference and cardiac metabolic risk factors such as hypertension, abnormal blood glucose and dyslipidaemia among middle-aged and elderly women. Methods: The cross-sectional study population consisted of 476 female participants aged 40-80 years, including 304 perimenopausal and 172 postmenopausal women. Calf circumference, body mass index (BMI), blood pressure, blood glucose and blood lipids were measured. Logistic regression analysis was used to evaluate the study aims. Results: Calf circumference was lower in postmenopausal than perimenopausal women, and postmenopausal women had the highest rates of hypertension, abnormal blood glucose and abnormal blood lipids. Pearson correlation coefficients showed that calf circumference was positively correlated with triglycerides (TGs), BMI, fasting plasma glucose (FPG),2-h plasma glucose, glycated haemoglobin (HbA1C), systolic blood pressure and diastolic blood pressure; and negatively correlated with high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC). The group with the lowest quantile of calf circumference had higher rates of hypertension (odds ratio (OR)2.14,95% confidence interval (CI)1.67-2.74),dysglycaemia (OR1.40,95%CI1.03-1.90) and dyslipidaemia (OR2.14,95%CI 1.86-2.46). Conclusion: In perimenopausal women, measurements of calf circumference can be used to predict the presence of cardiac metabolic risk factors, which can be detected by observing blood pressure, blood glucose, and blood lipids.

Trapping and release of NIR-active dye in porous silicon as a theranostic strategy for ROS photothermal monitoring and chronic wound management.

Reactive oxygen species (ROS)-sensitive theranostics hold great promise for personalized treatment of various diseases. However, most current theranostics rely on luminescence techniques with complex probe design, high background signals and bulky instruments. Herein, we propose a novel thermal signal-based theranostic for ROS monitoring by detecting the photothermal signal change of near-infrared (NIR)-active dye (IR820) that released from the porous silicon (PSi)-based carrier and demonstrate its application for synergistic theranostics of chronic wounds. Owing to the reduced energy level caused by J-aggregate formation and the improved non-radiative decay pathway, trapping of IR820 in calcium ion sealed PSi (I-CaPSi) exhibits significantly enhanced photothermal capability compared to free IR820. With the degradation of PSi induced by ROS, the trapped and aggregated IR820 is released to be dispersed and free state. Therefore, the decrease of photothermal signal in response to ROS stimuli can be recorded in real time. Using a portable smartphone equipped with a thermal camera, ROS levels at wounds can be monitored non-invasively and conveniently to indicate exacerbation or healing conditions. Moreover, the NIR-triggered smart delivery platform also triggers photothermal and photodynamic therapy to inhibit bacterial growth and exhibits bioactivity to promote cell migration and angiogenesis via the Si ions released from PSi. With the synergistic advantages of ROS-responsive property, pro-healing ability, anti-infection effect and excellent biosafety, the NIR-activated theranostic platform achieves convenient diagnosis and effective treatment in diabetic wound infection models in vivo. Overall, this work demonstrates a promising paradigm of I-CaPSi smart delivery platform with great clinical translation potential for home-based chronic wound theranostics.

Elevated Serum NOX2 Levels Contribute to Delayed Cerebral Ischemia and a Poor Prognosis After Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

Background: NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH. Methods: Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls. World Federation of Neurological Surgeons scale (WFNS) score and modified Fisher (mFisher) score were utilized to assess disease severity. Modified Rankin scale (mRS) score was used to evaluate the clinical prognosis at 90 days after aSAH. Relations of serum NOX2 levels to DCI and 90-day poor prognosis (mRS score of 3-6) were analyzed using multivariate analysis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability. Results: Serum NOX2 levels in aSAH patients, compared with healthy controls, were significantly increased, and were independently correlated with WFNS score, mFisher score and post-stroke 90-day mRS score. Patients with poor prognosis or DCI had significantly higher serum NOX2 levels than other remainders, and serum NOX2 levels independently predicted 90-day poor prognosis and DCI. Serum NOX2 had high prognosis and DCI predictive abilities, and their areas under ROC curve were similar to those of WFNS score and mFisher score. Conclusion: Serum NOX2 levels are significantly associated with hemorrhage severity, poor 90-day prognosis and DCI in aSAH patients. Hence, complement NOX2 may serve as a potential prognostic biomarker after aSAH.

α-MSH as a potential biomarker of severity and prognosis after intracerebral hemorrhage: A prospective cohort study.

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) exerts anti-inflammatory and brain protective effects. We determined plasma α-MSH concentrations and discovered the relationship between plasma α-MSH concentrations and severity plus clinical outcome after intracerebral hemorrhage (ICH). METHODS: A total of 117 ICH patients and 117 healthy controls were included in this study. Glasgow coma scale (GCS) score and hematoma volume were recorded to assess disease severity. We used Glasgow outcome scale (GOS) score to evaluate the 3-month clinical prognosis. And multivariate analysis was done to discern the relation of plasma α-MSH concentrations to disease severity plus poor prognosis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability. RESULTS: Plasma α-MSH concentrations in ICH patients, compared with healthy controls, were significantly decreased (median, 25.37 vs 46.80 pg/ml; P < 0.001), and were independently correlated with GCS score (t = 4.091, P < 0.001). Plasma α-MSH concentrations were highly correlated with GOS scores (ρ = 0.548, P < 0.001), were substantially lower with poor prognosis (GOS scores 1-3) than good prognosis, and efficiently discriminated patients at risk of poor prognosis (AUC ROC, 0.793; 95 % CI: 0.709-0.863). Using Youden method, plasma α-MSH concentrations < 23.63 pg/ml predicted poor prognosis with sensitivity of 72.7 % and specificity of 82.2 %. Alternatively, plasma α-MSH concentrations emerged as an independent predictor of poor prognosis with odds ratio of 0.888 (95 % CI: 0.793-0.995; P = 0.040). CONCLUSION: Plasma α-MSH concentrations are significantly associated with disease severity and poor 3-month prognosis in patients with ICH, indicating that plasma α-MSH may serve as a useful potential prognostic biomarker for ICH.

Porous Silicon Carrier Endowed with Photothermal and Therapeutic Effects for Synergistic Wound Disinfection.

Drug carriers endowed with photothermal effects will allow the drug delivery system to release drugs in a thermal-stimuli manner. In addition, the photothermal therapy (PTT) will also interplay with therapeutic drugs loaded in the carrier to exhibit synergistic bioactivity for various disease treatment. However, endowing the drug carrier with photothermal and synergistic therapeutic effects still has challenge. Herein, we demonstrate that surface modification of porous silicon (PSi) with polydopamine (PDA) could endow the classical drug carrier with a significant photothermal effect for advanced antibacterial therapy and wound disinfection. Specifically, the PSi surface interacts with a Cu2+/PDA complex via a simple and fast surface reduction-induced deposition method, forming the unique CuPDA coated PSi microcarrier (CuPPSi) without blocking the mesoporous structure. The CuPPSi carrier generates a higher near-infrared (NIR) photothermal efficiency and improved drug loading capacity owing to the abundant functional groups of PDA. Stimuli-responsive release of antibacterial Cu2+ and loaded curcumin (Cur) from CuPPSi can be realized under multiple stimuli including pH, reactive oxygen species and NIR laser irradition. Benefited from the carrier's intrinsic multimodal therapy, the CuPPSi-Cur platform exhibits amplified, broad-spectrum, and synergistic antibacterial effect, killing more than 98% for both Staphylococcus aureus and Escherichia coli at a mild PTT temperature (∼45 °C). Notably, the combined therapy promotes migration of fibroblasts with no significant cytotoxicity as revealed through cell experiments in vitro. In bacteria-infected mice model, efficient bacterial ablation and wound healing are further demonstrated with negligible side effects in vivo. Overall, the rational design of a drug carrier with photothermal and therapeutic effects provides a novel intervention for amplifing wound disinfection clinically.

Plasma SIRT3 as a Biomarker of Severity and Prognosis After Acute Intracerebral Hemorrhage: A Prospective Cohort Study.

Objective: SIRT3 may act as a brain-protective factor. We measured the plasma SIRT3 levels of patients with intracerebral hemorrhage (ICH) and further determined the relationship between plasma SIRT3 and clinical outcome plus severity of ICH. Methods: In this prospective cohort study, we quantified plasma SIRT3 levels in 105 ICH patients and 72 healthy controls. Glasgow Coma Scale (GCS) score and hematoma volume were used to assess severity. Poor prognosis was defined as a Glasgow Outcome Scale (GOS) score of 1-3 at 90 days after ICH. Results: Plasma SIRT3 levels were markedly lower in patients than in controls (median, 10.19 versus 13.17 ng/mL; P<0.001). Among all patients, plasma SIRT3 levels were independently correlated with hematoma volume (beta, -0.098; 95% confidence interval, -0.158--0.039; t, -3.282; P=0.001) and GCS score (beta, 0.465; 95% confidence interval, 0.107-0.823; t, 2.576; P=0.011). A total of 46 cases had a poor prognosis at post-stroke 90 days. The plasma levels of SIRT3 significantly decreased in patients with a poor prognosis, compared with those with a good prognosis (median, 6.1 versus 11.2 ng/mL; P<0.001). Plasma SIRT3 was an independent predictor for 90-day poor prognosis of patients (odds ratio, 0.837; 95% confidence interval, 0.708-0.990; P=0.038). Plasma SIRT3 levels distinguished the development of poor prognosis with area under receiver operating characteristic curve at 0.801 (95% confidence interval, 0.711-0.872) and plasma SIRT3 levels ≤7.38 ng/mL predicted poor prognosis with 63.04% sensitivity and 93.22% specificity. Conclusion: Declined plasma SIRT3 levels are highly associated with hemorrhagic severity and poor 90-day outcome, thus suggesting that plasma SIRT3 may serve as a potential prognostic biomarker for ICH.

Role of plasma Apo-J as a biomarker of severity and outcome after intracerebral hemorrhage: A prospective and cohort study.

BACKGROUND: Apolipoprotein J (Apo-J) may act as a neuroprotective factor after acute brain injury. We gauged plasma Apo-J concentrations in patients with acute intracerebral hemorrhage (ICH) and investigated its predictive value for 90-day outcome and disease severity. METHODS: This prospective cohort study included 123 ICH patients and 123 healthy controls. The severity of ICH was assessed using the Glasgow Coma Scale (GCS) score and hematoma volume. Poor outcome was referred to as a Glasgow Outcome Scale (GOS) score of 1-3 at 90 days after stroke. Multivariate analysis was performed to identify associations of plasma Apo-J concentrations with disease severity and poor outcome. RESULTS: The plasma Apo-J concentrations of patients were significantly higher than those of healthy controls (median, 95.50 mg/l versus 55.71 mg/l; P < 0.001), and were independently correlated with hematoma volume (t = 2.716; P = 0.008) and GCS score (t = -5.978; P < 0.001). Plasma Apo-J significantly differentiated patients at risk of poor outcome (area under receiver operating characteristic curve (AUC), 0.772; 95% confidence interval (CI), 0.688-0.843; P < 0.001), and its predictive ability was similar to those of GCS score (AUC, 0.851; 95% CI, 0.776-0.909; P = 0.056) and hematoma volume (AUC, 0.849; 95% CI, 0.774-0.907, P = 0.089). Using maximum Youden index, plasma Apo-J concentrations >113.21 mg/l distinguished the development of poor outcome, with a sensitivity of 67.3% and a specificity of 87.3%. Plasma Apo-J concentrations >113.21 mg/l (odds ratio, 4.042; 95% CI, 1.093-14.951; P = 0.036) and hematoma volume (odds ratio, 1.124; 95% CI, 1.014-1.247; P = 0.027) were independently associated with poor outcome. CONCLUSIONS: Plasma Apo-J concentrations are markedly associated with disease severity and 90-day poor outcome in ICH patients. Hence, plasma Apo-J is presumed to be used as a potential prognostic biomarker of ICH.

Elevated Plasma Complement C1q Levels Contribute to a Poor Prognosis After Acute Primary Intracerebral Hemorrhage: A Prospective Cohort Study.

Objective: The complement cascade is activated early following intracerebral hemorrhage (ICH) and causes acute brain injury. We intended to explore the effects of plasma complement component 1q (C1q) levels on hemorrhagic severity and functional outcome in ICH patients. Methods: In this prospective cohort study, we measured the plasma C1q levels of 101 ICH patients and 101 healthy controls. The Glasgow Coma Scale (GCS) score and hematoma volume were used to assess the ICH severity. Poor prognosis was referred to as a Glasgow Outcome Scale (GOS) score of 1-3 at three months following a stroke. A multivariate logistic regression model was configured to determine the independent relation of plasma C1q levels to severity and poor prognosis. Under receiver operating characteristic (ROC) curve, prognostic capability of plasma C1q levels was evaluated. Results: There was a significant elevation of plasma C1q levels in patients, as compared to controls [median (percentiles 25th-75th), 225.04 mg/l (156.10-280.15 mg/l) versus 88.18 mg/l (70.12-117.69 mg/l); P<0.001]. Plasma C1q levels of patients were independently related to GCS score (t =-3.281, P=0.001) and hematoma volume (t = 2.401, P=0.018), and were highly correlated with the GOS score at 3 months post-stroke (r=-0.658, P<0.001). Plasma C1q levels were obviously higher in poor prognosis patients than in other remainders (median percentiles 25th-75th), 278.40 mg/l (213.81-340.05 mg/l) versus 174.69 mg/l (141.21-239.93 mg/l); P<0.001). Under the ROC curve, plasma C1q levels significantly discriminated the development of poor prognosis (area under ROC curve 0.795; 95% confidence interval, 0.703-0.869; P<0.001). Using maximum Youden method, plasma C1q levels > 270.11 mg/l distinguished patients at risk of poor prognosis at 3 months with 56.52% sensitivity and 94.55% specificity. Meanwhile, the prognostic predictive ability of plasma C1q levels was equivalent to those of GCS score and hematoma volume (both P>0.05). Moreover, plasma C1q levels > 270.11 mg/l independently predicted a poor prognosis at 3 months (odds ratio, 4.821; 95% confidence interval, 1.211-19.200; P=0.026). Conclusion: Plasma C1q levels are closely related to the illness severity and poor prognosis of ICH at 3 months. Hence, complement C1q may play an important role in acute brain injury after ICH and plasma C1q may represent a promising prognostic predictor of ICH.

Plasma PRPC Levels Correlate With Severity and Prognosis of Intracerebral Hemorrhage.

Background: Cellular prion protein (PRPC) exerts brain-protective effects. We determined the relationship between plasma PRPC levels and disease severity plus clinical outcome after acute intracerebral hemorrhage (ICH). Methods: A total of 138 ICH patients and 138 healthy controls were included in this prospective, observational study. Hematoma volume and Glasgow coma scale (GCS) score were used to assess disease severity. Glasgow outcome scale (GOS) scores of 1-3 and 4-5 at 90 days after stroke were defined as a poor outcome and good outcome, respectively. Using multivariate analysis, we discerned the relation of plasma PRPC levels to disease severity and poor outcome. The receiver operating characteristic (ROC) curve was built to evaluate the prognostic predictive capability. Results: Plasma PRPC levels in ICH patients were significantly higher than those in healthy controls (median, 4.20 vs. 2.02 ng/ml; P < 0.001), and were independently correlated with GCS score (r = -0.645, P < 0.001) and hematoma volume (r = 0.627, P < 0.001). Plasma PRPC levels were highly correlated with GOS score (r = -0.762, P < 0.001), and were substantially higher in patients with poor outcomes than in those with the good outcomes. Using maximum Youden index, plasma PRPC levels >3.893 ng/ml distinguished the risk of poor outcome at 90 days, with a sensitivity of 86.4% and a specificity of 65.8% (area under the curve, 0.809; 95% confidence interval (CI), 0.737-0.881, P < 0.001). Plasma PRPC levels >3.893 ng/ml were independently associated with a poor 90-day outcome with an odds ratio of 12.278 (95% CI, 5.101-29.554). Conclusion: Elevated plasma PRPC levels are significantly associated with disease severity and poor 90-day outcome in ICH patients, indicating that plasma PRPC may be used as a potential prognostic biomarker after ICH.

Clinical features and risk factors of severely and critically ill patients with COVID-19.

BACKGROUND: As of June 1, 2020, over 370000 coronavirus disease 2019 (COVID-19) deaths have been reported to the World Health Organization. However, the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear. AIM: To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19. METHODS: A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan. Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups: The moderate group, severe group and critically ill group. Epidemiological data, demographic data, clinical symptoms and outcomes, complications, laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups. RESULTS: A total of 126 patients were enrolled. There were 59 in the moderate group, 49 in the severe group, and 18 in the critically ill group. Multivariate logistic regression analysis showed that age [odd ratio (OR) = 1.055, 95% (confidence interval) CI: 1.099-1.104], elevated neutrophil-to-lymphocyte ratios (OR = 4.019, 95%CI: 1.045-15.467) and elevated high-sensitivity cardiac troponin I (OR = 10.126, 95%CI: 1.088 -94.247) were high-risk factors. CONCLUSION: The following indicators can help clinicians identify patients with severe COVID-19 at an early stage: age, an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.

Periostin aggravates the early phase of traumatic brain injury via the MAPK/ERK pathway.

OBJECTIVES: Periostin is found associated with trauma severity and mortality following head injury. In this study, the role and mechanism of periostin in the traumatic brain injury were investigated. METHODS: Male Sprague-Dawley adult rats underwent sham or TBI modeling. Vehicle or recombinant periostin was administered intracerebroventricularly at 30 minutes post-TBI, and U0126, a specific MEK1/2 inhibitor, was administered intravenously at 30 minutes pre-TBI. Garcia neuroscore, limb function and brain water content assessments, as well as TUNEL and Western blotting assays were performed to evaluate the status of the above rats at 24 hours post-TBI. Finally, the motor test and Morris water maze test were performed to measure the effects of periostin and U0126 in the late phase of TBI. RESULTS: Periostin expression significantly increased 24 hours post-TBI. Treatment with R-periostin aggravated post-TBI neurobehavioral impairment, brain edema, induced apoptosis and raised the quantity of phospho-p38, phospho-JNK, phospho-ERK and MMP-9, and lowered the expression of ZO-1. However, U0126, a kind of inhibitor of MEK, lowered the quantities of phospho-ERK and MMP-9, raised the expression of ZO-1, and suppressed apoptosis. U0126 also ameliorated the neurobehavioral impairments and brain edema induced by R-periostin. Additionally, U0126 didn't inhibit the expression of periostin in the early phase of TBI model. IU0126 was also able to ameliorate the pathological conditions in the late phase of TBI. DISCUSSION: Periostin could aggravate neurobehavioral impairments and brain edema following TBI, and was involved in the early phase of TBI via the MAPK/ERK pathway.

Serum Hypoxia-Inducible Factor 1alpha Levels Correlate with Outcomes After Intracerebral Hemorrhage.

BACKGROUND: Serum hypoxia-inducible factor 1alpha (HIF-1α) is a key regulator in hypoxic and ischemic brain injury. We determined the relationship between serum HIF-1α levels and long-term prognosis plus severity of intracerebral hemorrhage (ICH). METHODS: A total of 97 ICH cases and 97 healthy controls were enrolled. Glasgow Coma Scale (GCS) score and hematoma volume were used to assess hemorrhagic severity. Glasgow Outcome Scale (GOS) score of 1-3 at post-stroke 90 days was defined as a poor outcome. RESULTS: Serum HIF-1α levels of ICH patients were significantly higher than those of healthy controls (median, 218.8 vs 105.4 pg/mL; P<0.001) and were substantially correlated with GCS score (r=-0.485, P<0.001), hematoma volume (r=0.357, P<0.001) and GOS score (r=-0.436, P<0.001). Serum HIF-1α levels >239.4 pg/mL discriminated patients at risk of 90-day poor outcome with sensitivity of 65.9% and specificity of 79.3% (area under the receiver operating characteristic curve, 0.725; 95% confidence interval, 0.625-0.811; P<0.001). Moreover, serum HIF-1α levels >239.4 pg/mL were independently associated with a poor 90-day outcome (odds ratio, 5.133; 95% confidence interval, 1.117-23.593; P=0.036). CONCLUSION: Serum HIF-1α, in close correlation with hemorrhagic severity and poor 90-day outcome, may serve as a potential prognostic biomarker for ICH.

Role of mean platelet volume in hypertriglyceridemia-induced acute pancreatitis during pregnancy.

BACKGROUND: Hypertriglyceridemia-induced acute pancreatitis during pregnancy (HTG-APP) is a rare but severe disease with high maternal-fetal mortality risk, which constitutes a systemic inflammatory process accompanied by thrombosis and bleeding disorders. However, the role of mean platelet volume (MPV) in HTG-APP remains unclear. METHODS: In the retrospective study, we collected 45 patients with HTG-APP as the HTG-APP group and 49 pregnant females with hypertriglyceridemia as the control group. MPV and other relevant variables at onset and remission were collected and compared. RESULTS: MPV were significantly higher in the HTG-APP group than in the control group (P < 0.001), and lower in remission than on onset (P = 0.002). According to the severity of acute pancreatitis, all subjects were classified into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups. There was a significant difference in MPV on onset among the three groups (P = 0.048), and the SAP patients had the highest levels of MPV. In addition, only in the SAP group, MPV was lower in remission than on onset (P = 0.010). Logistic regression analyses revealed that MPV was significantly associated with SAP (odds ratio = 2.077, 95% confdence interval, 1.038-4.154; P = 0.039). CONCLUSIONS: These results may indicate an important role of mean platelet volume in evaluating the severity of HTG-APP.

Effects of ipratropium bromide on the occurrence of postoperative respiratory complications in craniectomy patients with COPD: A nationwide multicenter retrospective study.

INTRODUCTION: Postoperative pulmonary complications (PPCs) are common and associated with increased morbidity, mortality, and medical cost. They are gaining increasing concerns among patients receiving neurological surgery. Chronic obstructive pulmonary disease (COPD) affect a large section of whole population and is also one of the risk factors of PPCs in the perioperative setting. Ipratropium bromide is the inhalation solution for the treatment of COPD. Studies showed the perioperative nebulization of ipratropium bromide could increase the lung function and decrease the incidence of postoperative pneumonia in COPD patients underwent thoracic surgery. The purpose of this study is to investigate the effect of perioperative nebulization of ipratropium bromide on PPCs in COPD patients underwent neurosurgical surgery. METHODS AND ANALYSIS: This study is a multicenter retrospective study in China. Patients who meet the inclusion/exclusion criteria are selected from 7 neurosurgical centers in China. According to whether ipratropium bromide is used in perioperative period, the patients are divided into exposure group and control group. The primary outcome is the incidence of postoperative pneumonia. Secondary outcomes are unplanned intubation, postoperative mechanical ventilation ≥ 48 hours, respiratory failure, atelectasis, death, and length of stay. ETHICS AND DISSEMINATION: This study was approved by the ethics committee (EC) of the School of Public Health, Fudan University, Shanghai, China. Waived by the ethics committee, no written consent form was obtained since we used the registry data. The study results will be communicated via publication. TRIAL REGISTRATION NUMBER: ChiCTR1900022552.

IRX1 hypermethylation promotes heart failure by inhibiting CXCL14 expression.

To identify the mechanism and functions of IRX1 in heart failure (HF) and provide evidence for new therapies. Bioinformatic analysis was performed to select target genes in HF cells compared to normal groups. Experimental rats were treated in a controllable manner to explore how IRX1 methylation accounted for this disease in vivo. Cardiac ultrasonic and morphologic examinations were conducted to test the mouse heart and evaluate the degree of cardiac impairment at in the level of organization. GSEA analysis revealed the relative enrichment of functions. Immunofluorescent assays, western blotting and qRT-PCR were used to determine the DNA methylation and expression levels. IRX1 was hypermethylated in heart failure and identified as a target gene by bioinformatic analysis. Transverse aortic constriction (TAC) induced heart failure in rats, while 5-aza-2'-deoxycytidine (5-Aza) alleviated heart failure in rats according to medical cardiac indexes. Western blotting and qRT-PCR revealed that a conspicuous difference in the expression of IRX1 and CXCL14 between HF and normal cardiac cells. As a result of gene methylation, left ventricular hypertrophy and cardiac fibrosis is usually accompanied by heart failure. Moreover, is the results implied that the demethylation of IRX1 improves heart failure in vivo and in vitro. IRX1 methylation induced damaged cardiac function and even heart failure, which has important implications for HF treatment and diagnosis.

[Observation on the application of ventilator internal circuit disinfection in mechanically ventilated patients].

OBJECTIVE: To understand the internal circuit contamination of ventilator in mechanical ventilation patients, to evaluate the effect of ventilator internal circuit disinfection and the impact on the incidence of ventilator-associated pneumonia (VAP). METHODS: A total of 39 patients with mechanical ventilation admitted to intensive care unit (ICU) of Hangzhou Geriatric Hospital from January 2017 to June 2018 were enrolled. Routine mechanical ventilation treatments for patients included pipeline replacement, aseptic operation, prevention of infection, etc. After 2 weeks of mechanical ventilation, the internal circuit of the ventilator was disinfected using the internal circuit sterilizer of the ventilator. Microorganism sampling and detection at 3 cm to the exhalation port of the internal circuit of the ventilator was performed before and after disinfection. The number of colonies was < 5 cfu/cm2 and no pathogenic bacteria could be detected. During the observation period, if the patient was complicated by VAP for anti-infective treatment, the ventilator with internal loop disinfection was replaced after infection control, and was incorporated again into the group for observation. The number of microbial colonies in the internal circuit of the ventilator before and after disinfection, the microbiological test pass rate and the incidences of VAP during the 2 weeks were observed. RESULTS: All 39 patients were included in the analysis, with 23 male and 16 female; with age of 65-97 years old, average (78.7±7.6) years old. Before the disinfection, 9 604 strains were detected in the internal circuit of the ventilator, including 8 687 strains of Gram-negative bacilli (90.4%), 902 strains of Gram-positive cocci (9.4%), and 15 strains of fungi (0.2%), which were detected in the lower respiratory tract of the patients. The strain concordance rate was 41%. The qualified rate of microbial detection in the internal circuit of the ventilator was 5.1%; 13 cases (33.3%) of VAP occurred during 2 weeks of mechanical ventilation. After disinfection, 785 strains of pathogens were detected in the internal circuit of the ventilator, and the number of colonies was significantly reduced compared with that before disinfection [cfu/cm2: 0 (0, 20) vs. 150 (15, 500), P < 0.01], of which 688 strains of Gram-negative bacilli (87.7%), 92 strains of Gram-positive cocci (11.7%) and 5 strains of fungi (0.6%) were found; the qualified rate of microbial detection in the internal circuit of ventilator reached 71.8%, which was significantly higher than that before disinfection (P < 0.01); 2 weeks after mechanical ventilation the incidence of VAP decreased slightly during the period [20.5% (8/39) vs. 33.3% (13/39)], but there was no significant difference (P > 0.05). CONCLUSIONS: The internal circuit of the ventilator can be used to detect the pathogen and the sputum culture of the patients on mechanical ventilation with a high consistency. The disinfection of the pathogen could significantly reduce the air pollution of the ventilator and reduce the occurrence of VAP in the patients.

Prognostic significance of serum translocator protein in patients with traumatic brain injury.

BACKGROUND: Translocator protein (TP) is related to inflammation and is involved in brain injury. The objective of this study was to ascertain whether serum TP concentrations are associated with the severity and prognosis of traumatic brain injury (TBI). METHODS: We quantified the serum concentrations of TP in 106 healthy controls and 106 patients with severe TBI. Recorded prognostic variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction, 6-month mortality and 6-month poor outcome (Glasgow Outcome Scale score of 1-3). Trauma severity was assessed by Glasgow coma scale (GCS) score. Extent of inflammatory response was indicated by serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and C-reactive protein (CRP) concentrations. RESULTS: Patients had significantly higher serum TP concentrations than controls. Among patients, serum TP concentrations strongly and independently correlated with GCS score and serum IL-6, TNF-a and CRP concentrations. Serum TP was identified as an independent predictor for the preceding prognostic variables, its prognostic predictive ability was similar to that of GCS score and it also significantly improved prognostic predictive ability of GCS score. CONCLUSION: Serum TP may be intimately linked with in inflammation, disease progression and poor prognosis in TBI patients.

Serum ST2 as a potential prognostic biomarker for traumatic brain injury.

BACKGROUND: ST2, a receptor of interleukin-33, is involved in inflammation. We discerned the relationship between serum soluble ST2 (sST2) concentrations, inflammation, severity and prognosis following traumatic brain injury (TBI). METHODS: We measured serum sST2, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl-terminal hydrolase L1 concentrations in 106 healthy controls and 106 severe TBI patients. We recorded long-term prognosis (i.e., 6-month mortality and functional outcome) and in-hospital major adverse events, including in-hospital mortality, acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction. RESULTS: sST2 concentrations were significantly higher in patients than in controls and were significantly correlated with Glasgow coma scale (GCS) score and the preceding biomarkers concentrations. Serum sST2 was an independent prognostic predictor and its predictive ability significantly exceeded those of serum interleukin-6, tumor necrosis factor-alpha and C-reactive protein concentrations and was similar to those of GCS scores and serum concentrations of other remaining biomarkers. Moreover, sST2 concentrations significantly improved predictive ability of GCS score. CONCLUSION: Increased serum sST2 concentrations are significantly related to inflammation, severity and prognosis, substantialized ST2 as a potential prognostic biomarker for TBI.