Construction of Bridged Benzazepines via Photo-Induced Dearomatization.

Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4-hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.

Splicing factor-mediated regulation patterns reveals biological characteristics and aid in predicting prognosis in acute myeloid leukemia.

BACKGROUND: Alternative splicing (AS) of RNA is a fundamental biological process that shapes protein diversity. Many non-characteristic AS events are involved in the onset and development of acute myeloid leukemia (AML). Abnormal alterations in splicing factors (SFs), which regulate the onset of AS events, affect the process of splicing regulation. Hence, it is important to explore the relationship between SFs and the clinical features and biological processes of patients with AML. METHODS: This study focused on SFs of the classical heterogeneous nuclear ribonucleoprotein (hnRNP) family and arginine and serine/arginine-rich (SR) splicing factor family. We explored the relationship between the regulation patterns associated with the expression of SFs and clinicopathological factors and biological behaviors of AML based on a multi-omics approach. The biological functions of SRSF10 in AML were further analyzed using clinical samples and in vitro experiments. RESULTS: Most SFs were upregulated in AML samples and were associated with poor prognosis. The four splicing regulation patterns were characterized by differences in immune function, tumor mutation, signaling pathway activity, prognosis, and predicted response to chemotherapy and immunotherapy. A risk score model was constructed and validated as an independent prognostic factor for AML. Overall survival was significantly shorter in the high-risk score group. In addition, we confirmed that SRSF10 expression was significantly up-regulated in clinical samples of AML, and knockdown of SRSF10 inhibited the proliferation of AML cells and promoted apoptosis and G1 phase arrest during the cell cycle. CONCLUSION: The analysis of splicing regulation patterns can help us better understand the differences in the tumor microenvironment of patients with AML and guide clinical decision-making and prognosis prediction. SRSF10 can be a potential therapeutic target and biomarker for AML.

Molecular subtypes predict therapeutic responses and identifying and validating diagnostic signatures based on machine learning in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological tumor derived from hematopoietic stem cells. The aim of this study is to analyze the biological characteristics and identify the diagnostic markers of CML. We obtained the expression profiles from the Gene Expression Omnibus (GEO) database and identified 210 differentially expressed genes (DEGs) between CML and normal samples. These DEGs are mainly enriched in immune-related pathways such as Th1 and Th2 cell differentiation, primary immunodeficiency, T cell receptor signaling pathway, antigen processing and presentation pathways. Based on these DEGs, we identified two molecular subtypes using a consensus clustering algorithm. Cluster A was an immunosuppressive phenotype with reduced immune cell infiltration and significant activation of metabolism-related pathways such as reactive oxygen species, glycolysis and mTORC1; Cluster B was an immune activating phenotype with increased infiltration of CD4 + and CD8 + T cells and NK cells, and increased activation of signaling pathways such as interferon gamma (IFN-γ) response, IL6-JAK-STAT3 and inflammatory response. Drug prediction results showed that patients in Cluster B had a higher therapeutic response to anti-PD-1 and anti-CTLA4 and were more sensitive to imatinib, nilotinib and dasatinib. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage Selection Operator (LASSO) and Random Forest (RF) algorithms identified 4 CML diagnostic genes (HDC, SMPDL3A, IRF4 and AQP3), and the risk score model constructed by these genes improved the diagnostic accuracy. We further validated the diagnostic value of the 4 genes and the risk score model in a clinical cohort, and the risk score can be used in the differential diagnosis of CML and other hematological malignancies. The risk score can also be used to identify molecular subtypes and predict response to imatinib treatment. These results reveal the characteristics of immunosuppression and metabolic reprogramming in CML patients, and the identification of molecular subtypes and biomarkers provides new ideas and insights for the clinical diagnosis and treatment.

Automatic Tree Height Measurement Based on Three-Dimensional Reconstruction Using Smartphone.

Tree height is a crucial structural parameter in forest inventory as it provides a basis for evaluating stock volume and growth status. In recent years, close-range photogrammetry based on smartphone has attracted attention from researchers due to its low cost and non-destructive characteristics. However, such methods have specific requirements for camera angle and distance during shooting, and pre-shooting operations such as camera calibration and placement of calibration boards are necessary, which could be inconvenient to operate in complex natural environments. We propose a tree height measurement method based on three-dimensional (3D) reconstruction. Firstly, an absolute depth map was obtained by combining ARCore and MidasNet. Secondly, Attention-UNet was improved by adding depth maps as network input to obtain tree mask. Thirdly, the color image and depth map were fused to obtain the 3D point cloud of the scene. Then, the tree point cloud was extracted using the tree mask. Finally, the tree height was measured by extracting the axis-aligned bounding box of the tree point cloud. We built the method into an Android app, demonstrating its efficiency and automation. Our approach achieves an average relative error of 3.20% within a shooting distance range of 2-17 m, meeting the accuracy requirements of forest survey.

Family function, self-efficacy, care hours per day, closeness and benefit finding among stroke caregivers in China: A moderated mediation model.

AIMS AND OBJECTIVES: The aim of this study was to explore the moderated mediation mechanism of the relationships among family function, self-efficacy, care hours per day, closeness and benefit finding in family caregivers of patients with stroke in China. BACKGROUND: Benefit finding can provide a new means of resolving depression among family members caring for an ill loved one. However, current research has paid little attention to the benefit finding of family caregivers of stroke patients in China. DESIGN: A cross-sectional study. METHODS: Three hundred fifty family caregivers of patients with stroke were recruited from community service centres and hospitals in Zhengzhou, China. The participants completed the family APGAR index, caregiver benefit finding scale and Chinese general self-efficacy scale during a study conducted in 2017. Descriptive analyses and a moderated mediation model were computed. Reporting adhered to the STROBE checklist. RESULTS: A total of 311 family caregivers completed this study. Closeness between family caregivers and patients with stroke moderated the relationship between family function and caregiver benefit finding. Self-efficacy partially mediated the relationship between family function and caregiver benefit finding; moreover, care hours per day moderated the mediation. CONCLUSION: This study shows important factors associated with benefit finding in family caregivers of patients with stroke. This indicates elements that could help improve benefit finding intervention programmes for family caregivers of patients with stroke. RELEVANCE TO CLINICAL PRACTICE: The findings in our study provide valuable information on benefit finding and indicate some interventions to improve the mental health of family caregivers of stroke patients.

Impact of connecting methods of continuous renal replacement therapy device on patients underwent extracorporeal membrane oxygenation: A retrospectively observational study.

OBJECTIVE: The objective of this study was to compare the safety and efficiency of different extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) connection methods. BACKGROUND: The number of patients receiving ECMO is increasing, and the fields of application are getting wider. However, patients receiving ECMO are prone to acute kidney injury and fluid overload requiring CRRT. There are few comparative studies of two different systems of connecting CRRT device and ECMO from safety and efficacy perspective. METHODS: This retrospective observational study included patients receiving ECMO in the extracorporeal life support centre of the First Affiliated Hospital of Nanjing Medical University from June, 2015, to December, 2020. Patients were divided into the parallel system group and integrated system group according to the connecting method between ECMO circuit and CRRT line. The outcomes were discharge survival rate, CRRT therapeutic dose completion rate, CRRT catheterisation time, CRRT initiating time, local bleeding at the CRRT catheter site, mean filter life, ECMO circuit thrombosis, ECMO air leakage, or blood leakage due to CRRT. RESULTS: Thirty patients in the parallel system group and 70 patients in the integrated system group were finally included. The discharge survival rate and CRRT therapeutic dose completion rate were not significantly different between the two groups. The parallel system group had significant longer CRRT initiating time (49.0 ± 12.1 min vs. 14.6 ± 2.1 min, P < 0.001) and shorter filter life (11.5 ± 3.2 h vs. 47.3 ± 14.0 h, P < 0.001) than the integrated system group. The occurrence rate of local bleeding was 93.3% in the parallel system group, and there is no bleeding case in the integrated system group. There was no case of ECMO circuit thrombosis from CRRT as well as ECMO air or blood leakage caused by CRRT in either group. ECMO therapy can be adapted by adjusting the position of the CRRT outlet in the integrated system. CONCLUSIONS: Connecting CRRT and ECMO as an integrated system might accelerate CRRT initiation, avoid local bleeding, and prolong filter life compared to the parallel system. The chance of developing CRRT-related ECMO circuit leak and thrombosis is manageable.

Rhodium-Catalyzed Deuterated Tsuji-Wilkinson Decarbonylation of Aldehydes with Deuterium Oxide.

The recent surge in the applications of deuterated drug candidates has rendered an urgent need for diverse deuterium labeling techniques. Herein, an efficient Rh-catalyzed deuterated Tsuji-Wilkinson decarbonylation of naturally available aldehydes with D2O is developed. In this reaction, D2O not only acts as a deuterated reagent and solvent but also promotes Rh-catalyzed decarbonylation. In addition, decarbonylative strategies for the synthesis of terminal monodeuterated alkenes from α,ß-unsaturated aldehydes are within reach.

A novel fatty acid metabolism-related signature identifies features of the tumor microenvironment and predicts clinical outcome in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is the most common malignancy of the hematological system, and there are currently a number of studies regarding abnormal alterations in energy metabolism, but fewer reports related to fatty acid metabolism (FAM) in AML. We therefore analyze the association of FAM and AML tumor development to explore targets for clinical prognosis prediction and identify those with potential therapeutic value. METHODS: The identification of AML patients with different fatty acid metabolism characteristics was based on a consensus clustering algorithm. The CIBERSORT algorithm was used to calculate the proportion of infiltrating immune cells. We used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a signature for predicting the prognosis of AML patients. The Genomics of Drug Sensitivity in Cancer database was used to predict the sensitivity of patient samples in high- and low-risk score groups to different chemotherapy drugs. RESULTS: The consensus clustering approach identified three molecular subtypes of FAM that exhibited significant differences in genomic features such as immunity, metabolism, and inflammation, as well as patient prognosis. The risk-score model we constructed accurately predicted patient outcomes, with area under the receiver operating characteristic curve values of 0.870, 0.878, and 0.950 at 1, 3, and 5 years, respectively. The validation cohort also confirmed the prognostic evaluation performance of the risk score. In addition, higher risk scores were associated with stronger fatty acid metabolisms, significantly higher expression levels of immune checkpoints, and significantly increased infiltration of immunosuppressive cells. Immune functions, such as inflammation promotion, para-inflammation, and type I/II interferon responses, were also significantly activated. These results demonstrated that immunotherapy targeting immune checkpoints and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and M2 macrophages, are more suitable for patients with high-risk scores. Finally, the prediction results of chemotherapeutic drugs showed that samples in the high-risk score group had greater treatment sensitivity to four chemotherapy drugs in vitro. CONCLUSIONS: The analysis of the molecular patterns of FAM effectively predicted patient prognosis and revealed various tumor microenvironment (TME) characteristics.

Impact of Ghrelin on Ventricular Arrhythmia and Related Mechanism After Myocardial Infarction.

INTRODUCTION: Ghrelin is an endogenous peptide with potential protective effects on ischemic heart. METHODS: Synthetic ghrelin was administered (100 µg·kg-1 subcutaneous injection, twice daily) for 4 weeks in a rat model of myocardial infarction (MI) with coronary artery occlusion. At the 5th week, electrocardiogram, monophasic action potentials and autonomic nerve function were evaluated. Cardiac tyrosine hydroxylase (TH) was determined by immunofluorescence staining. RESULTS: MI significantly increased sympathetic nerve activity (SNA) and ventricular arrhythmias, and prolonged APD dispersion and APD alternans (p < 0.01). Ghrelin treatment significantly increased ventricular fibrillation threshold (VFT), shortened APD dispersion and APD alternans, inhibited SNA and promoted vagus nerve activities (p < 0.01). Ghrelin also markedly reversed abnormal expression of TH in the peri-infarcted area of the heart (p < 0.01). DISCUSSION/CONCLUSION: Ghrelin provides a sustained electrophysiological protection by the increase of VFT and improvement of APD dispersion and APD alternans. The mechanism may be related to the regulation of autonomic nerve and sympathetic nerve remodeling. Thus, ghrelin represents a novel drug to prevent ventricular arrhythmia in ischemic heart disease.

Average mean arterial pressure in the first 6 hours of extracorporeal cardiopulmonary resuscitation in the prediction of the prognosis of neurological outcome: a single-center retrospective study.

OBJECTIVE: To study the correlation between the mean arterial pressure (MAP) level in the first 6 hours of extracorporeal cardiopulmonary resuscitation (ECPR) and patients' neurological outcomes. METHODS: Sex, age, basic comorbidities, the time from the first cardiac arrest to the start of CPR, the time from the first cardiac arrest to extracorporeal membrane oxygenation (ECMO), standardized ECMO flow, and the pH value at the beginning of ECMO and after 6 hours were recorded. MAP was recorded every 2 hours during the first 6 hours, and the average was calculated. The lactic acid clearance rate of the first 6 hours was calculated. Evaluated the neurological prognosis of patients at discharge. Then the patients were divided into groups according to their average MAP, and the above variables were compared in groups. RESULTS: Enrolled 63 adult ECPR patients. There were no statistically significant differences in sex, age, basic comorbidities, the time from the first cardiac arrest to the start of conventional CPR, the time from the first cardiac arrest to the start of ECMO, standardized ECMO flow, 6-hour lactic acid clearance rate, pH value at the sixth hour of operation between two groups. The pH value at the start of ECMO, survival rate, and good prognosis rate in low average MAP group were significantly lower. Low average MAP was associated with poor neurological outcomes (relative risk (RR) 1.50, 95% CI 1.17, 1.92). The RR of good neurological outcome for patients with average MAP ⩾65 mmHg was 5.91 (95% CI 1.45, 24.06), and the RR for average MAP ⩾100 mmHg was 1.18 (95% CI 0.19, 7.52). CONCLUSION: For ECPR patients, average MAP <65 mmHg in the first 6 hours of ECPR indicates a poor neurological prognosis. However, whether higher average MAP levels can improve the neurological prognosis of ECPR patient remains to be further studied.

Alarin alleviated cardiac fibrosis via attenuating oxidative stress in heart failure rats.

The present study was to explore whether alarin could alleviate heart failure (HF) and attenuate cardia fibrosis via inhibiting oxidative stress. The fibrosis of cardiac fibroblasts (CFs) was induced by angiotensin (Ang) II. HF models were induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague-Dawley rats. Alarin (1.0 nM/kg/d) was administrated by intraperitoneal injection for 28 days. The decreases of left ventricular (LV) ejection fraction (EF), fractional shortening (FS), the maximum of the first differentiation of LV pressure (LV ± dp/dtmax) and LV systolic pressure (LVSP), and the increases of LV volume in systole (LVVS), LV volume in diastole (LVVD), LV end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD) in MI rats were improved by alarin treatment. The increases in the expression levels of collagen I, collagen III, and transforming growth factor (TGF)-ß were inhibited by alarin treatment in CFs and in the hearts of MI rats. The levels of NADPH oxidase (Nox) activity, superoxide anions and malondialdehyde (MDA) levels were increased, and the level of superoxide dismutase (SOD) activity was reduced in Ang II-treated CFs, which were reversed by alarin. Nox1 overexpression reversed the effects of alarin on attenuating the increases of collagen I, collagen III and TGF-ß expression levels induced by Ang II in CFs. These results indicated that alarin improved HF and cardiac fibrosis via inhibiting oxidative stress in HF rats. Nox1 played important roles in the regulation of alarin effects on attenuating CFs fibrosis induced by Ang II.

Factors associated with non-compliance with breastfeeding recommendation: a retrospective survey in hepatitis B virus-infected mothers who had taken Nucleos(t)ide analogs during pregnancy.

BACKGROUND: We encourage Hepatitis B virus-infected mothers to breastfeed postpartum, even when continuing pregnancy category B nucleos(t)ide analogs (NAs) treatment. However, a large proportion of the Hepatitis B virus-infected mothers were noncompliant with this breastfeeding recommendation. This study aimed to investigate the factors associated with noncompliance with breastfeeding recommendation in Hepatitis B virus-infected mothers who had received NAs treatment during pregnancy. METHODS: A total of 155 mothers with chronic hepatitis B receiving NAs treatment for preventing mother-to-child transmission during the late gestation period were included and divided into exclusive breastfeeding (n = 63), mixed feeding (n = 34), and artificial feeding (n = 58) groups according to the postpartum feeding methods. Independent variables associated with feeding methods were analyzed using logistic regression analysis. RESULTS: Compared to the breastfeeding and mixed feeding groups, the artificial feeding group had significantly more multiparity, later postpartum timing of stopping NAs treatment, and a lower proportion of having knowledge of NAs medications (all P < 0.05). In addition, multivariable logistic regression analysis confirmed that multiparity, later postpartum timing of stopping NAs treatment, and lacking knowledge of medication were independent factors associated with noncompliance with breastfeeding recommendation. CONCLUSIONS: Hepatitis B virus-infected mothers who stopped NAs treatment at late postpartum period or had less knowledge of medication were more likely to be noncompliant with breastfeeding recommendation. Strengthening health education for participants taking NAs may be an important method to improve compliance with breastfeeding recommendation.

Using internet search data to explore the global public concerns in ankylosing spondylitis.

OBJECTIVE: This study explored the changes of global public interest in internet search of ankylosing spondylitis (AS) based on Google Trends (GT) data, in order to reflect the characteristics of AS itself. METHODS: GT was used to obtain the search popularity scores of the term 'AS' on a global scale, between January 2004 and December 2018, under the 'health' classification. Based on the global search data of AS provided by GT, the cosinor analysis was used to test whether there was seasonality in AS. RESULTS: In general, AS related search volume demonstrated a decreasing trend from January 2004 to December 2014 and then remain stable from January 2015 to December 2018. No obvious seasonal variations were detected in AS related search volume (amplitude=1.54; phase: month=3.9; low point: month=9.9; p>0.025), which peaked in April and bottomed out in October. The top 17 rising topics were adalimumab, spondylolisthesis, Morbus, Vladimir Mikhailovich Bekhterev, autoimmune disease, rheumatoid arthritis, ankylosis, HLA- B27 positive, Crohn's disease, rheumatology, spondylosis, arthritis, uveitis, rheumatism, sacroiliac, psoriatic arthritis and spondylitis. CONCLUSIONS: Globally, there is no significant seasonal variation in GT for AS. The top fast-growing topics related to AS may be beneficial for doctors to provide targeted health education of the disease to patients and their families.

The safety of antiviral therapy and drug withdrawal for the prevention of mother-to-child transmission of HBV during pregnancy.

The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. Chronic hepatitis B mothers at the immune-tolerant phase with HBV DNA levels >6 log10 IU/mL were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until PPW 52 for clinical and virological parameters of hepatitis flares. Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and PPW 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). A total of 104 of 118 mothers who completed the study, 50% (52/104) had postpartum-elevated ALT levels, which were mild and moderate except 6 of 104 (5.77%) of patients had levels ≥5 times the upper limit of normal; 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the frequency of ALT elevation was similar among the groups A vs B vs C (50.9% [27/53] vs 58.3% [14/24] vs 40.7% [11/27], respectively; P = .447), as well as the mean peak ALT level (108.4/74.1/126.7 U/L in groups A/B/C, respectively; P = .291). Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to PPW 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warranted as severe flares rarely occurred.

Allogeneic bone marrow-derived mesenchymal stromal cells for hepatitis B virus-related acute-on-chronic liver failure: A randomized controlled trial.

Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV-related ACLF were enrolled in this open-label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%-84.8%) versus 55.6% (95% confidence interval 42.3%-68.9%) for the SMT group (P = 0.03). There were no infusion-related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5-24 of follow-up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End-Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). CONCLUSION: Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).

A novel electrochemical aptamer-antibody sandwich assay for the detection of tau-381 in human serum.

Tau protein plays a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the assay to detect low concentrations of tau protein is a great challenge for the early diagnosis of AD. We will outline a novel aptamer-antibody sandwich assay based on an electrochemical biosensor for the detection of tau-381 in human serum. To improve the detection sensitivity, the aptamer-antibody sandwich assay for the detection of tau-381 was developed by using a tau antibody (anti-tau) and an aptamer specific to tau-381 as the recognition element and cysteamine-stabilized gold nanoparticles (AuNPs) for signal amplification. Differential pulse voltammetry (DPV) was employed to record the signal response of tau-381 with different concentrations. The tau-381 concentration ranged from 0.5 pM to 100 pM. The responses of DPV measurements showed excellent results in this dynamic range. This simple, rapid, highly sensitive and specific assay gave a low limit of detection (LOD) of 0.42 pM for tau-381. The feasibility and reliability of the assay were verified by testing tau-381 in human serum from patients with AD. Thus, this method could prove valuable in diagnosing AD within the early stages of the disease.

Scedosporium apiospermum infection: lethal complication after extracorporeal cardiopulmonary resuscitation.

In recent years, the development of extracorporeal membrane oxygenation (ECMO) technology has led to its extensive use in clinical practice. In particular, ECMO can play an important role in cardiopulmonary resuscitation (CPR). The American Heart Association CPR guidelines recommend its use in patients with cardiac arrest due to reversible disorders, along with high-quality CPR. This is called extracorporeal cardiopulmonary resuscitation (ECPR). However, it is important to be aware of the possibility of infection-related complications. Here, we report on a patient who suffered a cardiac arrest in hospital and was rescued with ECMO, but who subsequently developed an infection with Scedosporium apiospermum.

miR-200c regulates endothelin-1 induced PASMCs abnormal proliferation and apoptosis.

miR-200c is an antioncogene in multiple tumors. However, its function in the pathogenesis of pulmonary arterial hypertension (PAH) has not been thoroughly investigated nor understood. In this study, we discovered that miR-200c was able to substantially upregulate in pulmonary arterial smooth muscle cells (PASMCs) treated with endothelin-1 (ET-1). miR-200c also induced cell proliferation and suppressed cell apoptosis in PASMCs in vitro. However, miR-200c had no effect on G1/S/G2 transitions during the cell cycle. Furthermore, we identified miR-200c as a new regulator of the microtubule associated protein 2 (MAP-2) and zinc finger E-box binding homeobox1 (ZEB-1) in PASMCs. miR-200c inhibited MAP-2 and ZEB-1 expression by directly binding to their 3'-untranslated regions(3'UTR) according to luciferase assay results. Our findings provide novel insights into the mechanisms of PAH pathogenesis and potential molecular biomarkers for PAH diagnosis and treatment. © 2017 IUBMB Life, 69(11):877-886, 2017.

Simultaneous measurement of methyl tert-butyl ether and tert-butyl alcohol in human serum by headspace solid-phase microextraction gas chromatography-mass spectrometry.

The abundant production of methyl tert-butyl ether (MTBE) and its widespread use have led to an increase in the potential for human exposure. This work described a simple, fast, sensitive, reliable and low-cost method for the simultaneous measurement of MTBE and its metabolite, tert-butyl alcohol (TBA) in human serum by headspace solid-phase microextraction gas chromatography-mass spectrometry. Extraction conditions were optimized and 40 °C, 10 min, 250 rpm and 0.3 g NaCl for a 1 mL sample were the optimal conditions. This method showed good analytical performance in terms of sensitivity with limits of detection in serum (1 mL) of 0.03 µg/L for MTBE and 0.05 µg/L for TBA, accuracy (mean recovery values) from 75.8% to 85.8%, precision (relative standard deviations) <10% and sample stability (biodegradation) <10% after 28 days. A verification experiment proved the reproducibility and stability of this method as well. Finally the method was used to detect 212 specimens, and the internal dose levels for MTBE in human serum were presented in China.