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1.  Effect of Abnormal Fasting Plasma Glucose Level on All-Cause Mortality in Older Patients With Acute Myocardial Infarction: Results From the Beijing Elderly Acute Myocardial Infarction Study (BEAMIS) 
Mayo Clinic Proceedings  2011;86(2):94-104.
OBJECTIVE: To assess whether the relationship between abnormal fasting plasma glucose (FPG) levels and patient outcomes holds for both older men and older women with acute myocardial infarction (AMI).
PATIENTS AND METHODS: From April 1, 2004, to October 31, 2006, a total of 2016 consecutive older patients (age ≥65 years) presenting with AMI were screened. Of these patients, 1854 were consecutively enrolled in the study. Patients were categorized into 4 groups: the hypoglycemic group (FPG, ≤90.0 mg/dL [to convert to mmol/L, multiply by 0.0555]; n=443, 23.9%), the euglycemic group (FPG, 90.1-126.0 mg/dL; n=812, 43.8%), the mildly hyperglycemic group (FPG, 126.1-162.0 mg/dL; n=308, 16.6%), and the severely hyperglycemic group (FPG, ≥162.1 mg/dL; n=291, 15.7%). The primary outcomes were rates of in-hospital and 3-year mortality.
RESULTS: Female patients were older and had a higher incidence of diabetes mellitus but lower rates of smoking and use of invasive therapy. Men tended to have a higher frequency of hypoglycemia, whereas women tended to have a higher frequency of hyperglycemia. No significant difference was found in in-hospital (10.9% vs 9.1%; P=.36) or 3-year (24.5% vs 24.5%; P=.99) mortality between male and female patients, and FPG-associated mortality did not vary significantly by sex.
CONCLUSION: An increased FPG level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased FPG levels at admission could predict higher mortality rates regardless of sex. There was a striking U-shaped relationship between FPG levels and in-hospital and 3-year mortality. The effect of abnormal FPG level on outcomes among older patients with AMI did not vary significantly by sex.
An increased fasting plasma glucose level was associated with a relatively higher risk of in-hospital mortality in men but not in women. Nonetheless, increased and decreased fasting plasma glucose levels at admission could predict higher mortality rates regardless of sex.
doi:10.4065/mcp.2010.0473
PMCID: PMC3031433  PMID: 21282483
2.  Efficacy and Safety of Intravenous Urapidil for Older Hypertensive Patients with Acute Heart Failure: A Multicenter Randomized Controlled Trial 
Yonsei Medical Journal  2016;58(1):105-113.
Purpose
Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial.
Materials and Methods
Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared.
Results
Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar.
Conclusion
Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
doi:10.3349/ymj.2017.58.1.105
PMCID: PMC5122625  PMID: 27873502
Urapidil; hypertension; acute heart failure; randomized controlled trial
3.  Visualization, Quantification and Characterization of Caerulein-Induced Acute Pancreatitis in Rats by 3.0T Clinical MRI, Biochemistry and Histomorphology 
Theranostics  2017;7(2):285-294.
Purpose: To investigate whether Caerulein-induced acute pancreatitis (AP) in rats could be noninvasively studied by clinical magnetic resonance imaging (MRI) techniques and validated by enzymatic biochemistry and histomorphology.
Materials and Methods: The study was approved by the institutional animal ethical committee. The AP was induced in 26 rats by intraperitoneal injections of Caerulein, as compared to 6 normal rats. T2-weighted 3D MRI, T2 relaxation measurement and contrast enhanced T1-weighted MRI were performed at 3 Tesla. Pancreatic volume and contrast ratio of pancreas against surrounding tissues were measured by MRI. Animals were scarified at 3, 8, 24 and 48-hr respectively for analyses of serum lipase and amylase levels, and biliopancreatic perfusion-assisted histomorphology.
Results: The AP could be observed on MRI 3-hr onwards after Caerulein-administration. T2 relaxation within the pancreas was prolonged due to high water content or edema. Increase of vascular permeability was indicated by T1 contrast enhancement. Both edema and vascular permeability gradually recovered afterwards (p<0.05/0.01), paralleled by declining serum enzyme levels (p<0.05). Microscopy revealed cell vacuolization and edema for early stage, and increased inflammatory cell infiltration and acinar cell loss after 24 and 48-hr.
Conclusion: Multiparametric MRI techniques at 3.0T could facilitate noninvasive diagnosis and characterization of Caerulein induced AP in rats, as validated by a novel ex vivo method.
doi:10.7150/thno.16282
PMCID: PMC5197064  PMID: 28042334
MR cholangiopancreatography; acute pancreatitis; Caerulein; rats.
4.  Analysis of High-altitude Syndrome and the Underlying Gene Polymorphisms Associated with Acute Mountain Sickness after a Rapid Ascent to High-altitude 
Scientific Reports  2016;6:38323.
To investigated the objective indicators and potential genotypes for acute mountain sickness (AMS). 176 male subjects were evaluated for symptoms scores and physiological parameters at 3700 m. EPAS1 gene polymorphisms were explored and verified effects of potential genotypes on pulmonary function by inhaled budesonide. The incidence of AMS was 53.98% (95/176). The individuals who suffered from headache with anxiety and greater changes in heart rate (HR), the forced vital capacity (FVC), and mean flow velocity of basilar artery (Vm-BA), all of which were likely to develop AMS. The rs4953348 polymorphism of EPAS1 gene had a significant correlation with the SaO2 level and AMS, and a significant difference in the AG and GG genotype distribution between the AMS and non-AMS groups. The spirometric parameters were significantly lower, but HR (P = 0.036) and Vm-BA (P = 0.042) significantly higher in the AMS subjects with the G allele than those with the A allele. In summary, changes in HR (≥82 beats/min), FVC (≤4.2 Lt) and Vm-BA (≥43 cm/s) levels may serve as predictors for diagnosing AMS accompanied by high-altitude syndrome. The A allele of rs4953348 is a protective factor for AMS through HR and Vm-BA compensation, while the G allele may contribute to hypoxic pulmonary hypertension in AMS.
doi:10.1038/srep38323
PMCID: PMC5159877  PMID: 27982053
5.  Clinical features of upper gastrointestinal serrated lesions: An endoscopy database analysis of 98746 patients 
World Journal of Gastroenterology  2016;22(45):10038-10044.
AIM
To analyse the clinical features of patients with the serrated lesions in the upper gastrointestinal tract (UPGI) tract.
METHODS
Patients who underwent routine esophagogastroduodenoscopy (EGD) at the Digestive Endoscopy Centre of General Hospital, Tianjin Medical University between January 2011 and December 2015 were consecutively recruited. Patients with UPGI serrated lesions were consecutively identified. The patients’ demographics and histopathology were recorded. The colorectal findings for patients who underwent colonoscopy simultaneously or within six months were also extracted from the colonoscopy database. In addition, we analysed differences in colorectal neoplasia detection between the study patients and randomly selected patients matched for age and gender who did not exhibit serrated lesions and who also underwent colonoscopy in the same period.
RESULTS
A total of 21 patients out of 98746 patients (0.02%) who underwent EGD were confirmed to have serrated lesions with predominantly crenated, sawtooth-like configurations. The mean age of the 21 patients was (55.3 ± 17.2) years, and 11 patients were male (52.4%). In terms of the locations of the serrated lesions, 17 were found in the stomach (including 3 in the cardia, 9 in the corpus and 5 in the antrum), 3 were found in the duodenum, and 1 was found in the esophagus. Serrated lesions were found in different mucosal lesions, with 14 lesions were detected in polyps (8 hyperplastic polyps and 6 serrated adenomas with low grade dysplasia), 3 detected in Ménétrier gastropathy, 3 detected in an area of inflammation or ulcer, and 1 detected in the intramucosal carcinoma of the duodenum. In addition, colonoscopy data were available for 18 patients, and a significantly higher colorectal adenoma detection rate was observed in the UPGI serrated lesions group than in the randomly selected age- and gender-matched group without serrated lesions who also underwent colonoscopy in the same period (38.9% vs 11.1%, OR = 5.091, 95%CI: 1.534-16.890, P = 0.010). The detection rate of advanced adenoma was also higher in the UPGI serrated lesions group (22.2% vs 4.2%, OR = 6.571, 95%CI: 1.322-32.660, P = 0.028).
CONCLUSION
Serrated lesions in the UPGI were detected in various mucosal lesions with different pathological morphologies. Moreover colonoscopy is recommended for the detection of concurrent colorectal adenoma for these patients.
doi:10.3748/wjg.v22.i45.10038
PMCID: PMC5143750  PMID: 28018111
Clinical features; Upper gastrointestinal tract; Serrated lesions; Colorectal adenoma; Colorectal cancer
6.  Transient ulnar artery compression facilitates transradial access 
Medicine  2016;95(48):e5491.
Abstract
Background:
Unsuccessful radial artery puncture is one of the important causes of transradial procedure failure. Ulnar artery compression made the radial artery pulse stronger. Whether it would make transradial access easier, however, is uncertain.
Methods:
A prospective randomized controlled trial was conducted among 446 patients who planned for transradial cardiac catheterization. Patients were randomized to receiving either transient ulnar artery compression (UC) or standard treatment (standard) for half an hour prior to needle insertion (217 UC, 229 standard). The diameters of right radial artery and ulnar artery were measured by ultrasound on admission and before artery puncture. Primary endpoints included the number of attempts to access, the rate of first-pass success, and time for a successful access. Secondary endpoints were the number of difficult procedures, and the incidence of puncture failure.
Results:
The diameters of radial artery were larger after half an hour's ulnar artery compression, but there were no obvious changes in that of ulnar artery. As compared with standard group, the number of attempts was significantly decreased (1.42 ± 1.10 vs 2.97 ± 2.38, P <0.001), and the rate of first-pass success was greatly enhanced (73.27% vs 57.64%, P <0.001) in UC group. Meanwhile, the time for access was decreased (59 ± 15 seconds vs 71 ± 18 seconds, P <0.001) with UC. In addition, the proportion of difficult procedures of UC group was less than that of standard group (4.61% vs 10.92%, P = 0.013). No significant differences were found in failure rates of sheath insertion and puncture between the 2 groups.
Conclusion:
Transient ulnar artery compression enhances the efficacy and feasibility of radial artery intubatton in transradial catheterization.
doi:10.1097/MD.0000000000005491
PMCID: PMC5134798  PMID: 27902608
coronary heart disease; transradial catheterization; ulnar artery compression
7.  Association between plasma ADAMTS-7 levels and severity of disease in patients with stable obstructive coronary artery disease 
Medicine  2016;95(48):e5523.
Abstract
The metalloproteinase family of a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) was reported to be a novel locus associated with human coronary artery disease. This study aimed to investigate plasma ADAMTS-7 levels in stable obstructive CAD patients and elucidate the relationship between plasma ADAMTS-7 levels and the severity of CAD assessed by the Syntax score.
This was a single center cross-sectional study performed in 182 CAD patients. ELISA was used to measure plasma ADAMTS-7 levels. All patients were divided into subgroup according to the ADAMTS-7 median in this cohort: high group with ADAMTS-7 ≥0.99 ng/mL and low group with ADAMTS-7 <0.99 ng/mL. Furthermore, all patients were divided into tertiles according to their Syntax scores (low group: Syntax score ≤10.0; moderate group: 10.0 18.0). We followed up the participants continuously until the first major adverse cardiovascular event (MACE) for a mean time of 22.0 months.
Plasma ADAMTS-7 levels in the high Syntax score group were significantly higher compared with the low Syntax score group (3.29 [0.08–26.3] ng/mL vs 1.24 [0.15–8.78] ng/mL, P = 0.010). Plasma ADAMTS-7 levels were significantly positively correlated with the Syntax score tertiles (r = 0.157, P = 0.035). Logistic regression analysis indicated that the plasma ADAMTS-7 level was one of the independent predictors for the Syntax score tertiles (B = 1.118, 95% CI: 1.194–7.830, P = 0.020), together with HbA1c (B = 0.946, 95% CI: 1.248–5.312, P = 0.010), uric acid (B = –0.019, 95% CI: 0.974–0.988, P<0.001), and coronary artery calcium score (B = –0.001, 95% CI: 0.998–0.999, P < 0.001). Compared with the low ADAMTS-7 group, the high ADAMTS-7 group had significantly higher Syntax score (17.10±8.42 vs 14.96 ± 8.11, P = 0.047). Kaplan–Meier analysis showed patients in the high plasma ADAMTS-7 group tend to have a lower event-free survival rate than patients in the low plasma ADAMTS-7 group, unfortunately, no difference was detected (86.8% vs 88.0%, log rank = 0.314, P = 0.575).
The plasma ADAMTS-7 level was positively correlated with the Syntax score significantly. The elevated plasma ADAMTS-7 level may be involved in the severity of disease in patients with stable coronary artery disease.
doi:10.1097/MD.0000000000005523
PMCID: PMC5134802  PMID: 27902619
ADAMTS-7; coronary artery disease; MACE; syntax score
8.  Establishment of a Simple and Quick Method for Detecting Extended-Spectrum β-Lactamase (ESBL) Genes in Bacteria 
Extended-spectrum β-lactamase (ESBL) genes that render bacteria resistant to antibiotics are commonly detected using phenotype testing, which is time consuming and not sufficiently accurate. To establish a better method, we used phenotype testing to identify ESBL-positive bacterial strains and conducted PCR to screen for TEM (named after the patient Temoneira who provided the first sample), sulfhydryl reagent variable (SHV), cefotaxime (CTX)-M-1, and CTX-M-9, the 4 most common ESBL types and subtypes. We then performed multiplex PCR with 1 primer containing a biotin and hybridized the PCR products with gene-specific probes that were coupled with microbeads and coated with a specific fluorescence. The hybrids were linked to streptavidin-R-phycoerythrins (SA-PEs) and run through a flow cytometer, which sorted the fluorescently dyed microbeads and quantified the PEs. The results from single PCR, multiplex PCR, and cytometry were consistent with each other. We used this method to test 169 clinical specimens that had been determined for phenotypes and found 154 positive for genotypes, including 30 of the 45 samples that were negative for phenotypes. The CTX-M genotype tests alone, counting both positive and negative cases, showed 99.41% (168/169) consistency with the ESBL phenotype test. Thus, we have established a multiplex-PCR system as a simple and quick method that is high throughput and accurate for detecting 4 common ESBL types and subtypes.
doi:10.7171/jbt.16-2704-001
PMCID: PMC5026501  PMID: 27672351
multiplex PCR; flow fluorescence; drug-resistance gene; antibiotics
9.  Feasibility Study of Computational Fluid Dynamics Simulation of Coronary Computed Tomography Angiography Based on Dual-Source Computed Tomography 
Background
Adding functional features to morphological features offers a new method for non-invasive assessment of myocardial perfusion. This study aimed to explore technical routes of assessing the left coronary artery pressure gradient, wall shear stress distribution and blood flow velocity distribution, combining three-dimensional coronary model which was based on high resolution dual-source computed tomography (CT) with computational fluid dynamics (CFD) simulation.
Methods
Three cases of no obvious stenosis, mild stenosis and severe stenosis in left anterior descending (LAD) were enrolled. Images acquired on dual-source CT were input into software Mimics, ICEMCFD and FLUENT to simulate pressure gradient, wall shear stress distribution and blood flow velocity distribution. Measuring coronary enhancement ratio of coronary artery was to compare with pressure gradient.
Results
Results conformed to theoretical values and showed difference between normal and abnormal samples.
Conclusions
The study verified essential parameters and basic techniques in blood flow numerical simulation preliminarily. It was proved feasible.
doi:10.14740/jocmr2623w
PMCID: PMC5127214  PMID: 27924174
Dual-source CT; Coronary computed tomography angiography; Computational fluid dynamics; Pressure gradient; Wall shear stress distribution; Flow velocity distribution
10.  Pulmonary endothelial activation caused by extracellular histones contributes to neutrophil activation in acute respiratory distress syndrome 
Respiratory Research  2016;17:155.
Background
During the acute respiratory distress syndrome (ARDS), neutrophils play a central role in the pathogenesis, and their activation requires interaction with the endothelium. Extracellular histones have been recognized as pivotal inflammatory mediators. This study was to investigate the role of pulmonary endothelial activation during the extracellular histone-induced inflammatory response in ARDS.
Methods
ARDS was induced in male C57BL/6 mice by intravenous injection with lipopolysaccharide (LPS) or exogenous histones. Concurrent with LPS administration, anti-histone H4 antibody (anti-H4) or non-specific IgG was administered to study the role of extracellular histones. The circulating von Willebrand factor (vWF) and soluble thrombomodulin (sTM) were measured with ELISA kits at the preset time points. Myeloperoxidase (MPO) activity in lung tissue was measured with a MPO detection kit. The translocation of P-selectin and neutrophil infiltration were measured by immunohistochemical detection. For in vitro studies, histone H4 in the supernatant of mouse lung vascular endothelial cells (MLVECs) was measured by Western blot. The binding of extracellular histones with endothelial membrane was examined by confocal laser microscopy. Endothelial P-selectin translocation was measured by cell surface ELISA. Adhesion of neutrophils to MLVECs was assessed with a color video digital camera.
Results
The results showed that during LPS-induced ARDS extracellular histones caused endothelial and neutrophil activation, as seen by P-selectin translocation, release of vWF, an increase of circulating sTM, lung neutrophil infiltration and increased MPO activity. Extracellular histones directly bound and activated MLVECs in a dose-dependent manner. On the contrary, the direct stimulatory effect of exogenous histones on neutrophils was very limited, as measured by neutrophil adhesion and MPO activity. With the contribution of activated endothelium, extracellular histones could effectively activating neutrophils. Both inhibiting the endothelial activation with an anti-toll like receptor (TLR) antibody and inhibiting the interaction of the endothelium with neutrophil using an anti-P-selectin antibody decreased the degree of neutrophil activation.
Conclusions
Extracellular histones are pro-inflammatory mediators in LPS-induced ARDS in mice. In addition to direct action to neutrophils, extracellular histones promote neutrophil adhesion and subsequent activation by first activating the pulmonary endothelium via TLR signaling. Thus, endothelial activation is important for extracellular histone-induced inflammatory injury.
doi:10.1186/s12931-016-0472-y
PMCID: PMC5117496  PMID: 27871277
Extracellular histones; Acute respiratory distress syndrome; Inflammation; Endothelium; Neutrophil
11.  Effects of Shenlian extract on experimental atherosclerosis in ApoE-deficient mice based on ultrasound biomicroscopy 
Background
This study directly and dynamically investigated the effects of SL extract (i.e., a combination of Radix Salviae miltiorrhizae and Andrographis paniculata extract) on plaque progression in vivo by high resolution ultrasound biomicroscopy (UBM).
Methods
An atherosclerosis model was established by placing a perivascular collar on the right common carotid artery in apolipoprotein E-deficient (ApoE-/-) mice. Thickness, plaque area and local blood flow were observed by UBM, pathological changes were observed by histochemical staining, and lipid levels were measured by respective commercially available kits.
Results
Compared with the model group, the SL extract groups showed reduced wall thickness of the aortic arch (GC: P = 0.001, P = 0.002, and P < 0.001; LC: P < 0.001, P < 0.001, and P < 0.001; BC: P = 0.027, P = 0.017, and P = 0.003; respectively), which presented with retarded plaque progression of the cartoid artery with concordantly increased blood flow (P = 0.002 and P < 0.001) as visualized in vivo by UBM. Histological analysis confirmed the reduction of carotid atherosclerosis.
Conclusions
The SL extract inhibited the formation of atherosclerotic plaques in an ApoE-/- mice model by UBM analysis, and did so by effects that ameliorated local blood flow and improved blood lipid levels.
doi:10.1186/s12906-016-1449-6
PMCID: PMC5111256  PMID: 27846838
Atherosclerosis; Ultrasound biomicroscopy; Plaque; Hemodynamics; Radix Salviae miltiorrhizae; Andrographis paniculata
12.  The use of targeted exome sequencing in genetic diagnosis of young patients with severe hypercholesterolemia 
Scientific Reports  2016;6:36823.
Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia.
doi:10.1038/srep36823
PMCID: PMC5103295  PMID: 27830735
13.  Smart Nanocomposites of Cu-Hemin Metal-Organic Frameworks for Electrochemical Glucose Biosensing 
Scientific Reports  2016;6:36637.
Herein, a smart porous material, Cu-hemin metal-organic-frameworks (Cu-hemin MOFs), was synthesized via assembling of Cu2+ with hemin to load glucose oxidase (GOD) for electrochemical glucose biosensing for the first time. The formation of the Cu-hemin MOFs was verified by scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, N2 adsorption/desorption isotherms, UV-vis absorption spectroscopy, fluorescence spectroscopy, thermal analysis and electrochemical techniques. The results indicated that the Cu-hemin MOFs showed a ball-flower-like hollow cage structure with a large specific surface area and a large number of mesopores. A large number of GOD molecules could be successfully loaded in the pores of Cu-hemin MOFs to keep their bioactivity just like in a solution. The GOD/Cu-hemin MOFs exhibited both good performance toward oxygen reduction reaction via Cu-hemin MOFs and catalytic oxidation of glucose via GOD, superior to other GOD/MOFs and GOD/nanomaterials. Accordingly, the performance of GOD/Cu-hemin MOFs-based electrochemical glucose sensor was enhanced greatly, showing a wide linear range from 9.10 μM to 36.0 mM and a low detection limit of 2.73 μM. Moreover, the sensor showed satisfactory results in detection of glucose in human serum. This work provides a practical design of new electrochemical sensing platform based on MOFs and biomolecules.
doi:10.1038/srep36637
PMCID: PMC5095656  PMID: 27811998
14.  Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc Motion Segment in an Organ Culture 
BioMed Research International  2016;2016:2481712.
The development of mechanically active culture systems helps in understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures facilitate the application and control of mechanical loads. The purpose of this study was to establish a culturing method for rabbit IVD motion segments to observe the effect of static load on the whole disc organ. Segments were cultured in custom-made apparatuses under a constant, compressive load (3 kg) for 2 weeks. Tissue integrity, matrix synthesis, and matrix gene expression profile were assessed and compared with fresh one. The results showed ex vivo culturing of samples gradually destroyed the morphology. Proteoglycan contents and gene expression were decreased and downregulated obviously. However, immunohistochemical staining intensity and collagen type II gene expression were significantly enhanced and upregulated. In contrast, these trends were reversed under constant compression. These results indicated short-term static load stimulated the synthesis of type II collagen; however, constant compression led to progressive degeneration and specifically to proteoglycan. Through this study a loading and organ-culturing system for ex vivo rabbit IVD motion segments was developed, which can be used to study the effects of mechanical stimulation on the biology of IVDs and the pathomechanics of IVD degeneration.
doi:10.1155/2016/2481712
PMCID: PMC5107879  PMID: 27872846
15.  Prevalence and related factors of psychological distress among cancer inpatients using routine Distress Thermometer and Chinese Health Questionnaire screening 
Background
Clinical practice guidelines suggest routine screening for distress among cancer patients for immediate early psychiatric care. However, previous studies focusing on routine screening for psychological distress among cancer inpatients in Taiwan are scant. Thus, the aim of this study was to evaluate the prevalence and related factors of psychological distress and mental illness among cancer inpatients in Taiwan.
Patients and methods
This study was conducted as a retrospective chart review in a general hospital in southern Taiwan. Cancer inpatients were regularly screened by nursing staff using the Distress Thermometer and the 12-item Chinese Health Questionnaire. Positive screening results on either instrument were followed by a non-commanded referral to psychiatrists for clinical psychiatric diagnosis and treatment.
Results
Of the 810 participants in this study, 179 (22.1%) were recognized as having psychological distress. Younger age (odds ratio [OR] =1.82), having head and neck cancer (OR =2.43), and having not received chemotherapy (OR =1.58) were significantly related to psychological distress. Among the 56 patients (31.3%) with psychological distress who were referred to psychiatrists, the most common mental illness was adjustment disorder (n=22, 39.2%), followed by major depressive disorder (n=13, 23.2%), depressive disorder not otherwise specified (n=6, 10.7%), and anxiety disorder not otherwise specified (n=4, 7.1%).
Conclusion
Our study indicated that cancer inpatients with psychological distress were more likely to be younger in age, have head and neck cancer, and have not received chemotherapy. The most common psychiatric disorder was adjustment disorder. Early detection of psychological distress and prompt psychiatric consultation and management are very important for cancer inpatients.
doi:10.2147/NDT.S118667
PMCID: PMC5087777  PMID: 27822049
psychological distress; cancer inpatients; prevalence; related factors; Distress Thermometer; Chinese Health Questionnaire
16.  Large outbreak of herpangina in children caused by enterovirus in summer of 2015 in Hangzhou, China 
Scientific Reports  2016;6:35388.
Herpangina, usually caused by coxsackie virus A, is prevalent in children spreading through the fecal-oral transmission and the respiratory droplets dissemination. Also, it is mostly asymptomatic and self-limiting. In our study, we found that large outbreak of herpangina in children occurred in the summer of 2015 in Hangzhou, China. From May 1th to August 31th, a total of 10 210 children were diagnosed with herpangina in Children’s Hospital of Zhejiang University School of Medicine. 2 310 throat swabs were collected and tested for enterovirus detection by real-time RT-PCR, while 1 651 cases were positive with the rate of 71.5%. Based on VP1 gene or 5′UTR region sequences, Coxsackievirus A2, A4, A6, A10, B2, B4 and echovirus 30 were detected in these cases. More importantly, Coxsackievirus A2 may be the major subtype of enterovirus resulting in children with herpangina in hangzhou, China.
doi:10.1038/srep35388
PMCID: PMC5067559  PMID: 27752104
17.  Influence of magnetoplasmonic γ-Fe2O3/Au core/shell nanoparticles on low-field nuclear magnetic resonance 
Scientific Reports  2016;6:35477.
Magnetoplasmonic nanoparticles, composed of a plasmonic layer and a magnetic core, have been widely shown as promising contrast agents for magnetic resonance imaging (MRI) applications. However, their application in low-field nuclear magnetic resonance (LFNMR) research remains scarce. Here we synthesised γ-Fe2O3/Au core/shell (γ-Fe2O3@Au) nanoparticles and subsequently used them in a homemade, high-Tc, superconducting quantum interference device (SQUID) LFNMR system. Remarkably, we found that both the proton spin–lattice relaxation time (T1) and proton spin–spin relaxation time (T2) were influenced by the presence of γ-Fe2O3@Au nanoparticles. Unlike the spin–spin relaxation rate (1/T2), the spin–lattice relaxation rate (1/T1) was found to be further enhanced upon exposing the γ-Fe2O3@Au nanoparticles to 532 nm light during NMR measurements. We showed that the photothermal effect of the plasmonic gold layer after absorbing light energy was responsible for the observed change in T1. This result reveals a promising method to actively control the contrast of T1 and T2 in low-field (LF) MRI applications.
doi:10.1038/srep35477
PMCID: PMC5067577  PMID: 27752101
18.  Image Quality and Radiation Dose for Prospectively Triggered Coronary CT Angiography: 128-Slice Single-Source CT versus First-Generation 64-Slice Dual-Source CT 
Scientific Reports  2016;6:34795.
This study sought to compare the image quality and radiation dose of coronary computed tomography angiography (CCTA) from prospectively triggered 128-slice CT (128-MSCT) versus dual-source 64-slice CT (DSCT). The study was approved by the Medical Ethics Committee at Tongji Medical College of Huazhong University of Science and Technology. Eighty consecutive patients with stable heart rates lower than 70 bpm were enrolled. Forty patients were scanned with 128-MSCT, and the other 40 patients were scanned with DSCT. Two radiologists independently assessed the image quality in segments (diameter >1 mm) according to a three-point scale (1: excellent; 2: moderate; 3: insufficient). The CCTA radiation dose was calculated. Eighty patients with 526 segments in the 128-MSCT group and 544 segments in the DSCT group were evaluated. The image quality 1, 2 and 3 scores were 91.6%, 6.9% and 1.5%, respectively, for the 128-MSCT group and 97.6%, 1.7% and 0.7%, respectively, for the DSCT group, and there was a statistically significant inter-group difference (P ≤ 0.001). The effective doses were 3.0 mSv in the 128-MSCT group and 4.5 mSv in the DSCT group (P ≤ 0.001). Compared with DSCT, CCTA with prospectively triggered 128-MSCT had adequate image quality and a 33.3% lower radiation dose.
doi:10.1038/srep34795
PMCID: PMC5067634  PMID: 27752040
19.  P53 inhibitor pifithrin-α prevents the renal tubular epithelial cells against injury 
The injury and repair of renal tubular epithelial cells play an important role in the pathological process of acute kidney injury (AKI). This study aimed to clarify the role of cell cycle change in renal tubular epithelial cell injury and repair in vivo and in vitro. Sprague-Dawley rats received bilateral renal pedicle clamping for 45 min (ischemia) followed by reperfusion. Pifithrin-α, a p53 inhibitor, was administered at 24 h before renal ischemia and 3 and 14 days after reperfusion. Results showed the tubular epithelial cells in M phase increased significantly at 2 h to 72 h after ischemia/reperfusion (I/R), while pifithrin-α decreased them. Renal I/R caused renal tubular epithelial damage in rats, which was improved by pifithrin-α. The α-SMA mRNA expression was up-regulated significantly after I/R, while it was down-regulated by pifithrin-α.NRK-52E cells were cultured in vitro, cell damage was induced by addition of TNF-α, and then cells were treated with pifithrin-α. Cells treated with TNF-α alone in G2/M phase increased significantly, but they were reduced in the presence of pifithrin-α. In NRK-52E cells treated with pifithrin-α for 6 h, NGAL mRNA expression was significantly lower than in cells without pifithrin-α treatment. After NRK-52E cells were treated with pifithrin-α for 24 h, α-SMA and FN mRNA expression was significantly lower than in cells without the treatment. In summary, pifithrin-α can facilitate the progression of renal tubular epithelial cells through G2/M phase, protecting them against injury.
PMCID: PMC5095300  PMID: 27829991
Acute kidney injury (AKI); renal tubular epithelial cell; cell cycle; G2/M phase; pifithrin-α
20.  Molecular epidemiological study of enteroviruses associated with encephalitis in children from Hangzhou, China 
Medicine  2016;95(40):e4870.
Abstract
Enterovirus (EV) has over 100 serotypes of species A–D, which can cause various symptoms in infants. Enterovirus encephalitis (EVE) is serve disease with high morbidity and mortality in children. To well define the epidemiology of EVE, we wanted to know more about EV and EV molecular typing by conducting this study in Hangzhou.
Cerebrospinal fluid samples were collected from children with diagnosis of encephalitis. Meanwhile, one-step real-time RT-PCR was used for the detection of EV, and we also identified the serotypes of EV by using gene sequencing of VP1 or 5′UTR region.
A total of 126 CSF specimens were tested and EV was detected in 26 specimens (20.6%). The molecular typing results showed different types of EV strains including Coxsackievirus B2, Coxsackievirus B3, Echovirus 5, Echovirus 16, Echovirus 18, Echovirus 30, and all EV isolates belonging to the human EV species B.
According to the sequence of VP1 and 5′UTR region, E30 may be major cause of children's EVE in Hangzhou, China.
doi:10.1097/MD.0000000000004870
PMCID: PMC5059043  PMID: 27749541
children; enterovirus; enterovirus encephalitis; PCR
21.  Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc Motion Segment in Ex vivo Organ Culture 
Chinese Medical Journal  2016;129(19):2338-2346.
Background:
The development of mechanically active culture systems helps increase the understanding of the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion segment cultures allow for preservation of the native IVD structure, and adjacent vertebral bodies facilitate the application and control of mechanical loads. The purpose of this study was to establish loading and organ culture methods for rabbit IVD motion segments to study the effect of static load on the whole disc organ.
Methods:
IVD motion segments were harvested from rabbit lumbar spines and cultured in no-loading 6-well plates (control conditions) or custom-made apparatuses under a constant, compressive load (3 kg, 0.5 MPa) for up to 14 days. Tissue integrity, matrix synthesis, and the matrix gene expression profile were assessed after 3, 7, and 14 days of culturing and compared with those of fresh tissues.
Results:
The results showed that ex vivo culturing of motion segments preserved tissue integrity under no-loading conditions for 14 days whereas the static load gradually destroyed the morphology after 3 days. Proteoglycan contents were decreased under both conditions, with a more obvious decrease under static load, and proteoglycan gene expression was also downregulated. However, under static load, immunohistochemical staining intensity and collagen Type II alpha 1 (COL2A1) gene expression were significantly enhanced (61.54 ± 5.91, P = 0.035) and upregulated (1.195 ± 0.040, P = 0.000), respectively, compared with those in the controls (P < 0.05). In contrast, under constant compression, these trends were reversed. Our initial results indicated that short-term static load stimulated the synthesis of collagen Type II alpha 1; however, sustained constant compression led to progressive degeneration and specifically to a decreased proteoglycan content.
Conclusions:
A loading and organ culture system for ex vivo rabbit IVD motion segments was developed. Using this system, we were able to study the effects of mechanical stimulation on the biology of IVDs, as well as the pathomechanics of IVD degeneration.
doi:10.4103/0366-6999.190666
PMCID: PMC5040021  PMID: 27647194
Disc Degeneration; Intervertebral Disc; Motion Segment; Organ Culture; Static Load
22.  Negative prognostic impact of low absolute CD4+ T cell counts in peripheral blood in mantle cell lymphoma 
Cancer Science  2016;107(10):1471-1476.
Tumor microenvironment and host immunity are closely related to outcome in patients with mantle cell lymphoma (MCL). However, few researchers have focused on the prognostic value of peripheral blood lymphocyte subsets counts. The purpose of this study was to investigate the prognostic value of lymphocyte subsets and absolute monocyte counts. Sixty‐eight patients were analyzed retrospectively. Absolute CD4+ T cell counts (ACD4C), CD8+ T cell counts, nature killer cell counts, and CD4/CD8 ratios were assessed by peripheral blood flow cytometry and correlated with clinical parameters and long‐term outcomes. The median follow‐up for all patients was 21 months and the median survival time was 44 months. The overall survival (OS) rate at 1, 3, and 5 years was 80%, 51%, and 41%, respectively. In our cohort, high absolute monocyte count, and low ACD4C and CD4/CD8 ratio were associated with unfavorable OS (P = 0.029, P = 0.027, and P = 0.045, respectively) by univariate analysis. Multivariate analysis indicated that low ACD4C was a significant predictor of unfavorable OS (P = 0.004) independent of the simplified MCL International Prognostic Index (P = 0.048) in patients treated with or without rituximab (P = 0.011). Low CD4+ T cell counts proved to be a significant predictor of unfavorable OS in patients with MCL.
doi:10.1111/cas.13020
PMCID: PMC5084668  PMID: 27465799
CD4+ T cell; mantle cell lymphoma; overall survival; prognosis; T‐cell subsets
23.  The Effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on Alcohol-Induced Liver Injury 
Previous studies have shown that fruits have different effects on alcohol metabolism and alcohol-induced liver injury. The present work selected three fruits and aimed at studying the effects of Syzygium samarangense, Passiflora edulis and Solanum muricatum on alcohol-induced liver injury in mice. The animals were treated daily with alcohol and fruit juices for fifteen days. Chronic treatment with alcohol increased the levels of aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), triglyceride (TG), malondialdehyde (MDA), and decreased total protein (TP). Histopathological evaluation also showed that ethanol induced extensive fat droplets in hepatocyte cytoplasm. Syzygium samarangense and Passiflora edulis normalized various biochemical parameters. Solanum muricatum increased the level of ALT and induced infiltration of inflammatory cells in the liver. These results strongly suggest that treatment with Syzygium samarangense and Passiflora edulis could protect liver from the injury of alcohol, while Solanum muricatum could aggravate the damage.
doi:10.3390/ijms17101616
PMCID: PMC5085649  PMID: 27681723
alcohol; liver injury; Syzygium samarangense; Passiflora edulis; Solanum muricatum
24.  Cobalt Oxide and Cobalt‐Graphitic Carbon Core–Shell Based Catalysts with Remarkably High Oxygen Reduction Reaction Activity 
Advanced Science  2016;3(9):1600060.
The vital role of ethylenediaminetetraacetic acid on the structure and the oxygen reduction reaction activity of the non‐precious‐metal‐based pyrolyzed catalyst is reported and elaborated. The resultant catalyst can overtake the performance of commercial Pt/C catalyst in an alkaline medium.
doi:10.1002/advs.201600060
PMCID: PMC5039978  PMID: 27711264
cobalt; core–shell structure; ethylenediaminetetraacetic acid; non‐precious catalyst; oxygen reduction reaction
25.  Complications of ultrasound-guided percutaneous microwave ablation of renal cell carcinoma 
OncoTargets and therapy  2016;9:5903-5909.
Purpose
To retrospectively review the complications of ultrasound (US)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma.
Patients and methods
In this study, 101 patients with 105 tumors seen from April 2006 to Feb 2014 were enrolled retrospectively. The patients were treated with US-guided percutaneous MWA and were followed up with contrast-enhanced US and computed tomography or magnetic resonance imaging at 1, 3, and 6 months and every 6 months thereafter.
Results
Technical success was achieved in 99 of 105 tumors (94.3%). The median follow-up time was 25 (range 1.13–93.23) months. Among the 105 tumors, 26 complications in 24.8% of patients and 23 minor complications (Clavien–Dindo Grades I and II) in 21.9% of patients were noted, accounting for 88.5% of all complications. All the minor complications were cured. Three major complications (Clavien–Dindo Grade ≥III) occurred in 2.9% of the patients, accounting for 11.5% of all complications: hydrothorax in two patients and bowel injury in one. The two patients who had hydrothorax post-MWA had a history of cirrhosis and were treated with catheter drainage. The bowel injury was treated surgically. In all patients, the changes in serum creatinine and urea nitrogen levels from before to after the procedure were small.
Conclusion
US-guided percutaneous MWA is a beneficial treatment for renal cell carcinoma in selected patients; however, if the renal tumor is close to the bowel, or the patient has serious comorbidities or has undergone abdominal surgery, the procedure must be performed more carefully.
doi:10.2147/OTT.S109783
PMCID: PMC5045230  PMID: 27713644
microwave ablation; renal cell; complications; carcinoma

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