Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase.

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55-/- mice display clinical manifestations of Meckel-Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55-/- mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel-Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

Impact of complicated myocardial injury on the clinical outcome of severe or critically ill COVID-19 patients / 中华心血管病杂志

Objective: To analyze the clinical characteristics of the severe or critically ill patients with novel coronavirus pneumonia (COVID-19), and evaluate the impact of complicated myocardial injury on the prognosis of these patients. Methods: A retrospective study was conducted in 54 patients who admitted to Tongji hospital from February 3, 2020 to February 24, 2020 and met the criteria of severe or critical conditions of COVID-19. The clinical characteristics and hospital mortality rate were analyzed and compared between the patients with or without myocardial injury, which was defined with 3 times higher serum cardiac troponin value. Results: The age of the 54 patients was 68.0(59.8, 74.3) years. Among all the patients, 24 (44.4%) patients were complicated with hypertension, 13 (24.1%) with diabetes, 8 (14.8%) with coronary heart disease, and 3 (5.6%) with previous cerebral infarction. During hospitalization, 24 (44.4%) of the patients were complicated with myocardial injury and 26 (48.1%) patients died in hospital. In-hospital mortality was significantly higher in patients with myocardial injury than in patients without myocardial injury (14 (60.9%) vs. 8 (25.8%), P=0.013). Moreover, the levels of C-reactive protein (153.6 (80.3, 240.7) ng/L vs. 49.8 (15.9, 101.9) ng/L) and N-terminal pro-B-type natriuretic peptide (852.0 (400.0, 2 315.3) ng/L vs. 197.0 (115.3, 631.0) ng/L) were significantly higher than patients without myocardial injury (all P<0.01). Conclusions: Prevalence of myocardial injury is high among severe or critically ill COVID-19 patients. Severe or critically ill COVID-19 patients with myocardial injury face a significantly higher risk of in-hospital mortality. The study suggests that it is important to monitor and manage the myocardial injury during hospitalization for severe or critically ill COVID-19 patients.

Rab7 regulates primary cilia disassembly through cilia excision.

The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly. Depletion of Rab7 potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence. Moreover, Rab7 performs an essential role in cilia disassembly; knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Further, we demonstrate that Rab7 depletion significantly suppresses cilia tip excision, referred to as cilia ectocytosis, which has been identified as required for cilia disassembly. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, our results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.

The complete mitochondrial genome of the largest amphipod, Alicella gigantea: Insight into its phylogenetic relationships and deep sea adaptive characters.

Alicella gigantea (Alicelloidae) is a scavenger with the largest body size among amphipods. It is a participant in the foodweb of deepsea ecosystem and distributed with vast bathymetric and geographic ranges. In this study, the mitochondrial genome of A. gigantea was completely assembled and characterized. The complete sequence has a total length of 16,851 bp, comprising the usual eukaryotic components, with 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and 2 noncoding control regions (CRs). The gene rearrangement and reverse nucleotide strand bias of its mitochondrial genome are similar to those observed in the deepsea amphipod Eurythenes maldoror (Eurytheneidae), but different from the characters of Halice sp. MT-2017 (Dexaminoidea), an inhabitant of a deeper environment. Phylogenetic analysis indicates that A. gigantea occupies the basal branch of deepsea species-E. maldoror and Hirondellea gigas. This phylogeny supports the hypothesis that the evolution of hadal amphipods has undergone a transition from the abyssal depth. Compared to 41 available shallow water equivalents, the four accessible mitochondrial genomes from the deep sea, including the one produced in this study, show significantly fewer charged amino acids in the 13 PCGs, which suggests an adaption to the deepsea environment.

Induction of cell-cycle arrest and apoptosis in human cholangiocarcinoma cells by pristimerin.

Pristimerin, a triterpenoid isolated from Celastraceae and Hippocrateaceae, is known to induce cytotoxicity in several cancer cell lines. However, whether pristimerin can induce apoptosis in cholangiocarcinoma cells and the underlying mechanism remain unexplored. We assessed the function of human cholangiocarcinoma QBC and RBE cell lines using various experimental methods such as the cell viability assay to elucidate the viability of cells, flow cytometry to detect the death rate of cells, and Western blot analysis to evaluate the expression of cell cycle-related proteins and autophagy-related proteins. Human cholangiocarcinoma QBC cells were transplanted to nude mice to establish an animal model, and the effect of pristimerin on tumor growth in this model was observed. QBC and RBE cell lines treated with pristimerin (0, 5, 10, and 20 µmol/L) demonstrated the induction of apoptosis in a dose-dependent manner. The cell viability assay revealed a reduction in the cell viability with an increase in the pristimerin concentration. Similarly, flow cytometry revealed a gradual increase in the cell death rate with an increase in the pristimerin concentration. In addition, pristimerin significantly lowered the expression of apoptosis-related proteins (Bcl-2, Bcl-xL, and procaspase-3), but increased the Bax expression. Furthermore, pristimerin resulted in the G0/G1 cell-cycle arrest, reducing the expression of cell cycle-related proteins (cyclin E, CDK2, and CDK4), and increased the expression of autophagy-related proteins (LC3) in QBC cell line. Treatment with pristimerin could inhibit tumor growth in the nude mouse model. Overall, this study suggests the potential effect of pristimerin on the cell-cycle arrest and apoptosis in human cholangiocarcinoma cells.

HIV-positive patient receiving living related renal transplantation : a report of one case and literature review / 中华器官移植杂志

Objective To summarize the outcomes and clinical experiences of renal transplantation in human immunodeficiency virus (HIV)-positive patients .Methods The clinical data were retrospectively analyzed for one HIV-positive case of renal transplantation .Diagnosed as chronic renal insufficiency 1 year ago ,he received hemodialysis .After a positive screen for HIV ,he received highly active antiretroviral therapy (HAART) and HIV RNA turned negative 3 months later .CD4 + T cell count was 331 cell/μl at pre-operation and there was no HIV-rated opportunistic infection or cancer . Her mother donated her kidney . Basiliximab and steroid pulse therapy were used preoperatively and immunosuppressants were used after transplantation , including tacrolimus , corticosteroids and mycophenolate mofetil .Results The kidney was transplanted successfully and serum creatinine declined to a normal level at day 4 after transplantation .Because of an interaction between efaverenz and tacrolimus ,the blood concentration of tacrolimus was extremely low and the dose of tacrolimus had to be raised to 0 .2 mg/(kg·d) .Antiroviral therapy remained unchanged .No rejection and other complications were observed .And HIV RNA remained negative .Conclusions Renal transplantation is optimal for HIV-positive patients whose HIV status is completely under control .However ,drug interactions needs to be considered during perioperative and postoperative periods .

Microtubule asters anchored by FSD1 control axoneme assembly and ciliogenesis.

Defective ciliogenesis causes human developmental diseases termed ciliopathies. Microtubule (MT) asters originating from centrosomes in mitosis ensure the fidelity of cell division by positioning the spindle apparatus. However, the function of microtubule asters in interphase remains largely unknown. Here, we reveal an essential role of MT asters in transition zone (TZ) assembly during ciliogenesis. We demonstrate that the centrosome protein FSD1, whose biological function is largely unknown, anchors MT asters to interphase centrosomes by binding to microtubules. FSD1 knockdown causes defective ciliogenesis and affects embryonic development in vertebrates. We further show that disruption of MT aster anchorage by depleting FSD1 or other known anchoring proteins delocalizes the TZ assembly factor Cep290 from centriolar satellites, and causes TZ assembly defects. Thus, our study establishes FSD1 as a MT aster anchorage protein and reveals an important function of MT asters anchored by FSD1 in TZ assembly during ciliogenesis.

The value of diffusion tensor imaging in early diagnosis of chronic allograft nephropathy and monitoring graft fibrosis in rats / 中华放射学杂志

Objective To estimate the value of diffusion tensor imaging (DTI) in early diagnosis of chronic allograft nephropathy (CAN) and monitoring of graft fibrosis in rat models . Methods Thirty CAN rat models were established as experimental group by transplanting Fisher donor kidneys into Lewis recipients. Thirty Lewis rats that received Lewis kidneys served as control group. Serum creatinine (SCr) was monitored regularly every two weeks from 14 days after transplantation. Eight rats were randomly selected by random number table method and underwent DTI examination at 4, 12, 20 weeks after modeling. DTI scans were performed on the renal cortex and medulla to measure apparent diffusion coefficient (ADC) and fractional anisotropy (FA). From the remaining 22 rats in each group, 6 rats were randomly selected and underwent pathological analysis at 4, 12, 20 weeks after modeling. Histological changes in the kidney were evaluated by chronic allograft damage index (CADI) scores. The expression of alpha-smooth muscle actin (α-SMA) and Vimentin were quantitatively measured. The differences in creatinine, DTI parameters, CADI score, α-SMA, Vimentin expression level were analyzed by two independent samples t test in two groups, the differences among CADI score, α-SMA, Vimentin expression level of the experimental group were compared using ANOVA. The correlations among DTI parameters and CADI score, α-SMA and Vimentin expression level were analyzed using Pearson analysis. Results The creatinine in the experimental group increased continuously, and the creatinine in the control group showed no significant increase. The difference in creatinine between the two groups was statistically significant from 8th week after operation (P＜0.01). There was no obvious difference in the size and signal intensity of transplanted kidneys in control group at different time points. Compared with the control group, the graft kidney in the experimental group at the 4 weeks demonstrated increased signal intensity with mild increased volume of kidney, and the boundaries between cortex and medulla were not clear. The cortex and medulla showed gradually increased signal intensity, heterogeneous signal distribution and marginal haziness over time. The ADC and FA value of renal cortex and medulla in experimental group were significantly lower than those in control group at 4, 12, 20 weeks (P＜0.05). The ADC and FA values of the cortex and medulla gradually decreased in the experimental group over time, while the values of the parameters in the control group did not show a significant decrease. The ADC and FA values of the cortex and medulla were negatively correlated with the scores of CADI, and the expression level of α-SMA, Vimentin in the experimental group(r=－0.50 to －0.85, P＜0.01).Conclusion DTI can be an effective technique for early diagnosis of CAN and monitoring of graft fibrosis process.

Global Longitudinal Strain at Rest for Detection of Coronary Artery Disease in Patients without Diabetes Mellitus / 华中科技大学学报（医学）（英德文版）

Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD).However,the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown.In the present study,211 patients with suspected CAD were prospectively included,with DM patients excluded.All patients underwent echocardiography and subsequently coronary angiography within 3 days.Left ventricular (LV) GLSs were quantified by 2D STE.Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model.Critical CAD was defined as an area stenosis ≥70％ in ≥1 epicardial coronary artery (≥50％ in left main coronary artery).Totally 145 patients were diagnosed as having critical CAD by coronary angiography.Significant differences were observed in all strain parameters between patients with and without critical CAD.The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of-19.05％ with sensitivity of 78.1％ and specificity of 72.7％,which increased to 0.926 after exclusion of apical segments (cut-off value-18.66％;sensitivity 84.4％ and specificity 81.8％).The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries.The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery,left anterior descending (LAD) artery and right coronary artery (RCA),in order of diagnostic accuracy,was 0.818 for LCX,0.764 for LAD and 0.723 for RCA,respectively.In conclusion,in non-DM patients with suspected CAD,GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy,and a higher cut-off point than reported before should be used.Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS.It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.

Global Longitudinal Strain at Rest for Detection of Coronary Artery Disease in Patients without Diabetes Mellitus / 华中科技大学学报（医学）（英德文版）

Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD).However,the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown.In the present study,211 patients with suspected CAD were prospectively included,with DM patients excluded.All patients underwent echocardiography and subsequently coronary angiography within 3 days.Left ventricular (LV) GLSs were quantified by 2D STE.Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model.Critical CAD was defined as an area stenosis ≥70％ in ≥1 epicardial coronary artery (≥50％ in left main coronary artery).Totally 145 patients were diagnosed as having critical CAD by coronary angiography.Significant differences were observed in all strain parameters between patients with and without critical CAD.The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of-19.05％ with sensitivity of 78.1％ and specificity of 72.7％,which increased to 0.926 after exclusion of apical segments (cut-off value-18.66％;sensitivity 84.4％ and specificity 81.8％).The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries.The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery,left anterior descending (LAD) artery and right coronary artery (RCA),in order of diagnostic accuracy,was 0.818 for LCX,0.764 for LAD and 0.723 for RCA,respectively.In conclusion,in non-DM patients with suspected CAD,GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy,and a higher cut-off point than reported before should be used.Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS.It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.

The role and mechanism of SDF-1/CXCR4 signaling pathway in rat model of chronic renal allograft rejection / 中华器官移植杂志

Objective To investigate the role and mechanism of SDF-1/CXCR4 in the development of chronic rejection (CR) in rat models.Methods CR rat models were established using Fisher 344 to Lewis rats.In the blank control group (n=10),Lewis rats getting isotransplantation were treated with Cyclosporine A.CR rat models were established in positive group (n=10) and the rats were treated with Cyclosporine A.CR rat models were also established in CXCR4 antagonism group (n=10) and the rats were treated with both Cyclosporine A and AMD3100 (1 mg/kg).The serum creatinine levels were monitored every week.Kidney grafts were harvested 12 weeks after transplantation for histological analysis.We evaluated graft injuries using chronic allograft damage index (CADI) scores.Q-PCR and Western blotting were used to measure CXCR4,TGF-β1/Smad3 signaling pathway and α-smooth muscle actin (α-SMA) expression in renal allograft tissues.Results The serum creatinine levels in blank control group and CXCR4 antagonism group were significantly lower than those in positive control group (P<0.05).The blank control group and CXCR4 antagonism group presented milder pathological manifestations of CR.The CADI score in CXCR4 antagonism group was 3.54,which was lower than that of positive control group (P<0.05).The expression of biological markers in TGF-β1/Smad3 signaling pathway and SDF-1/CXCR4 signaling pathway was significantly lower in blank control group and CXCR4 antagonism group than in positive control group (P<0.05).Conclusion SDF-1/CXCR4 signaling pathway may play a crucial role in the development of CR.The usage of SDF-1/CXCR4 antagonist can protect renal allograft by inhibiting the TGF-β1/Smad3 pathway.Therefore,antagonism of CXCR4 may provide a novel way to prevent the development of CR.

Determination of content and encapsulation efficiency of leuprolideacetate microspheres / 中国生化药物杂志

Objective To establish a determination method for leuprolide acetate microspheres. Methods HPLC was performed on Inertsil ODS-SP (150×4.6 mm×5μm) with mobile phase consist of 0.1 mol/L of Ammonium Dihydrogen Phosphate(adjust its pH to 7.00±0.05 with Ammonium Hydroxide) and Acetonitrile in ratio of 3:1(V/V),and the flow rate was 1.0 mL/min.The wavelength was 220 nm and column temperature was 30℃. The injection volume was 20 μL. Results The linear range of leuprolide acetate was 20.0-160.0μg/mL (r=0.9999) with an average recovery of 99.80%,RSD=0.63%(n=9). Conclusion The method of HPLC was accurate,reliable and specific, which could be used to determinate the assay of leuprolide acetate microspheres and for quality control of microspheres.

Risk factors of infected pancreatic necrosis secondary to severe acute pancreatitis.

BACKGROUND: Severe acute pancreatitis (SAP) remains a clinical challenge with considerable morbidity and mortality. An early identification of infected pancreatic necrosis (IPN), a life-threatening evolution secondary to SAP, is obliged for a more preferable prognosis. Thus, the present study was conducted to identify the risk factors of IPN secondary to SAP. METHODS: The clinical data of patients with SAP were retrospectively analyzed. Univariate and multivariate logistic regression analyses were sequentially performed to assess the associations between the variables and the development of IPN secondary to SAP. A receiver operating characteristic (ROC) curve was created for each of the qualified independent risk factors. RESULTS: Of the 115 eligible patients, 39 (33.9%) progressed to IPN, and the overall in-hospital mortality was 11.3% (13/115). The early enteral nutrition (EEN) (P=0.0092, OR=0.264), maximum intra-abdominal pressure (IAP) (P=0.0398, OR=1.131) and maximum D-dimer level (P=0.0001, OR=1.006) in the first three consecutive days were independent risk factors associated with IPN secondary to SAP. The area under ROC curve (AUC) was 0.774 for the maximum D-dimer level in the first three consecutive days and the sensitivity was 90% and the specificity was 58% at a cut-off value of 933.5 µg/L; the AUC was 0.831 for the maximum IAP in the first three consecutive days and the sensitivity was 95% and specificity was 58% at a cut-off value of 13.5 mmHg. CONCLUSIONS: The present study suggested that the maximum D-dimer level and/or maximum IAP in the first three consecutive days after admission were risk factors of IPN secondary to SAP; an EEN might be helpful to prevent the progression of IPN secondary to SAP.

High-density lipoprotein cholesterol and in-hospital mortality in patients with acute aortic dissection / 华中科技大学学报（医学）（英德文版）

The association between high-density lipoprotein cholesterol (HDL-C) and mortality in patients with acute aortic dissection (AAD) is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group (n=585), low HDL-C group (n=343) had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group (21.6% vs. 12.6%, log-rank=10.869, P=0.001). After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference (adjusted hazard ratio, 1.23; 95% confidence interval, 0.86-1.77; P=0.259). Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.

Correlation study between four vessel regulate factors and white finger evaluating in workers exposed to hand-arm vibration / 中国职业医学

OBJECTIVE: To analyze the correlation between four vessel regulate factors and vibration-induced white finger( VWF) evaluating in workers exposed to hand-arm vibration,and discuss the value of regulate factors for VWF screening.METHODS: Using typical sampling method,77 male workers exposed to hand-arm vibration with more than 1 year of polish work from a metalwork factory were selected as the study subjects. Based on the workers' self-report,they were divided into VWF group( 43 workers) and non-VWF group( 34 workers). The venous blood from center elbow was collected and plasma was separated. The plasma level of endothelin( ET) was detected by radioimmunoassay. The plasma levels of transforming growth factor beta( TGF-β),soluble intercellular adhesion molecule-1( s ICAM-1) and 5-hydroxytryptamine( 5-HT) were detected by enzyme-linked immunosorbent assay. The regulate factors for evaluating VWF were screened and the new multivariable model index

CYP2C8-derived epoxyeicosatrienoic acids decrease oxidative stress-induced endothelial apoptosis in development of atherosclerosis: Role of Nrf2 activation / 华中科技大学学报（医学）（英德文版）

The aim of the present study is to investigate how cytochrome P450 enzymes (CYP) 2C8-derived epoxyeicosatrienoic acids (EETs) regulate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and protect against oxidative stress-induced endothelial injuries in the development and progression of atherosclerosis. In this study, cultured human umbilical vein endothelial cells (HUVECs) were transfected with CYP2C8 or pretreated with exogenous EETs (1 μmol/L) before TNF-α (20 ng/mL) stimulation. Apoptosis and intracellular ROS production were determined by flow cytometry. The expression levels of ROS-associated NAD(P)H subunits gp91 and p47, the anti-oxidative enzyme catalase (CAT), Nrf2, heme oxygenase-1 (HO-1) and endothelial nitric oxide synthase (eNOS) were detected by Western blotting. The results showed that CYP2C8-derived EETs decreased apoptosis of HUVECs treated with TNF-α. Pretreatment with 11, 12-EET also significantly blocked TNF-α-induced ROS production. In addition, 11, 12-EET decreased oxidative stress-induced apoptosis. Furthermore, the ability of 11, 12-EET to protect cells against TNF-α-induced apoptosis via oxidative stress was abrogated by transient transfection with Nrf2-specific small interfering RNA (siRNA). In conclusion, CYP2C8-derived EETs prevented TNF-α-induced HUVECs apoptosis via inhibition of oxidative stress associated with the Nrf2 signaling.

Analysis of single nucleotide polymorphisms at IL-6-174 and TNF-β NcoI in Chinese Han children in Guangzhou, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the single nucleotide polymorphisms (SNPs) at interleukin 6 (IL-6)-174 and TNF-β NcoI in Chinese Han children in Guangzhou, China and to provide basic information for study on the association between IL-6-174 and TNF-β NcoI polymorphisms and systemic inflammatory response syndrome (SIRS).</p><p><b>METHODS</b>Allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism were used to determine the SNPs at IL-6-174 and TNF-β NcoI in 481 children selected from the Han population in Guangzhou in 2012. Genotype analysis and comparison with other populations were made with reference to relevant literature.</p><p><b>RESULTS</b>Chinese Han children in Guangzhou had only GG genotype at IL-6-174, and the SNP at this locus was rare or not seen in the Han population in Guangzhou. At TNF-β NcoI, the frequencies of TNF-β 1*1, TNF-β 1*2, and TNF-β 2*2 genotypes were 24.7%, 49.7%, and 25.6%, respectively. The sample distribution was in accordance with Hardy-Weinberg equilibrium. The TNF-β 1 allele frequency was significantly higher in Guangzhou Han population than in European and American white population (P<0.05).</p><p><b>CONCLUSIONS</b>TNF-β NcoI SNP is prevalent in the Han population in Guangzhou, and the distribution of alleles is significantly different from that in the white population. The sample from an Hardy-Weinberg equilibrium population can be further used for study on the association between TNF-β NcoI SNP and SIRS in Chinese Han children in Guangzhou. IL-6-174 SNP is rare or not seen in the Han population in Guangzhou, so SNP at this locus cannot be selected for disease association analysis.</p>