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15 March 2017, Volume 45 Issue 3 Previous Issue    Next Issue

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The effect of triptolide on HIF1α and VEGF expressions under hypoxia in human umbilical vein endothelial cells TIAN Yuan, ZHANG Miao-miao, SHI Wen-tao, LI Shen, WANG Yu-chuan, HE Yu-kun, LI Wei-dong△ 2017, 45 (3):  225-228.  doi: 10.11958/20160773 Abstract ( 1069 )   PDF (877KB) ( 3728 )   Abstract: Objective To investigate the effect of triptolide (TP) on the expression of hypoxia inducible factor 1 alpha(HIF1α) and vascular endothelial growth factor (VEGF) in the human umbilical vein endothelial cells (HUVECs) under hypoxia. Methods (1) HUVECs were treated with 0, 40, 80, 160 and 320 nmol/L TP (named with hypoxia group, TP40 group, TP80 group, TP160 group and TP320 group, respectively) under the hypoxic condition (37 ℃, 5% CO2, 1% O2, 94%N2) for culturing 12 hours. Meanwhile, cells cultured under normoxia condition (without TP added) were set as the normoxia group. Western blot assay was used to detect the expression of HIF1α in each group. (2) The cells were divided into normal control group, hypoxia group and TP80 group. The immunofluorescence method was performed to detect the localization of HIF1α in cells. (3) Expressions of VEGF were detected by Western blot assay in TP80 group and hypoxia group. (4) The cells were divided into hypoxia group, TP80 group, TP80 +KF20 group (80 nmol/L TP and 20 μmol/L KC7F2), and TP80+KF30 group (80 nmol/L TP and 30 μmol/L KC7F2). After 12- hour culturing, Western blot assay was used to detect the expressions of HIF1α and VEGF in each group. Results (1) Under the normoxia condition, no HIF1α was detected in HUVECs. The expression level of HIF1α was significantly increased in TP80 group than that in hypoxia group (P < 0.05),while there was no significant change in expression of hypoxia HIF1α in TP160 group and TP320 group compared with that of hypoxic group. (2) The immunofluorescence result showed that HIF1α was mainly expressed in the nucleus. (3) The expression of VEGF was significantly increased in TP80 group than that in hypoxia group (P < 0.05). (4) After theintervention of KC7F2, HIF1α and VEGF expression levels were significantly decreased in the TP80+KF20 group and the TP80+ KF30 group than those in the TP80 group (P < 0.05). Conclusion TP can improve the expression of HIF1α and VEGF to accelerate the proliferation of endothelial cells under hypoxia condition. Related Articles | Metrics

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The inhibitory effect of PNS on brain 3-NT formation in vitro XIAO Chen1,2, SUN Li1,2?, CAO Shan-shan1,2, LIANG Hao1,2, CHENG Yan1,2 2017, 45 (3):  229-233.  doi: 10.11958/20161334 Abstract ( 879 )   PDF (599KB) ( 4053 )   Abstract: Objective To study the inhibitory effect of panax notoginseng saponins (PNS) on 3-nitrotyrosine (3-NT) formation in brain induced by heme/NO2 －/H2O2 or ONOO － pathways in vitro. Methods According to the two major pathways of 3-NT formation in vivo, the models of protein nitration induced by heme/NaNO2/H2O2 or ONOO － system were established, respectively, in vitro. Bovine serum albumin (BSA)/rat plasma protein or rat brain homogenate protein were utilized as reactive substrates in both systems. Samples were divided into blank-control group, 3-NT group and PNS group(including low-, medium- and high-concentration subgroups). In 3-NT group, samples were exposed to heme /NaNO2 /H2O2 or ONOO－ system, respectively, at 37 ℃ for 30 min, whereas in PNS group, samples were pre-incubated with PNS (at final concentrations of 50 mg/L, 100 mg/L, and 200 mg/L) at 37 ℃ for 5 min before the nitrating system exposure. The 3-NT level in each group was detected by Western blot assy. Results Compared with the blank-control group, both heme/NaNO2/H2O2 and ONOO－ system can induce significant 3-NT generation in BSA/ rat plasma protein or rat brain homogenate protein (P＜0.05). Compared with model group, PNS pre-treatment markedly inhibited 3-NT expression in BSA/rat plasma protein in a dose-dependent manner (P＜0.05), the inhibitory effect of low intervention on the level of 3-NT in rat brain homogenate protein was not significant (P＞0.05). Medium- and high-concentrations of PNS pre-treatment markedly inhibited 3-NT accumulation, with maximum effect at the concentration of 200 mg/L (P＜0.05). Conclusion Medium- and highconcentrations of PNS can inhibit 3-NT formation in brain tissue mediated by either heme/NO2－/H2O2 or ONOO－ pathways,implying that potential neuroprotective action against 3- NT involves pathological conditions, like trauma, stroke, and neurodegenerative diseases. Related Articles | Metrics

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The dynamic change and significance of apoptosis on lung alveolar macrophages in pulmonary fibrosis model mice LI Xin1, LI Qi1,2, LI Yi1, SU Cheng-cheng1, ZHOU Xin3, PENG Shou-chun1, WEI Lu-qing1△, JI Wen-jie1△ 2017, 45 (3):  234-238.  doi: 10.11958/20161506 Abstract ( 1306 )   PDF (1014KB) ( 4718 )   Abstract： Objective To observe the dynamic change and significance of apoptosis levels in the alveolar macrophages(AM) of the bleomycin-induced pulmonary fibrosis model mice. Methods A total of 100 mice were randomly divided into control group (n=50) and model group (n=50). The model group was received with bleomycin at 2.5 mg/kg via oropharyngeal instillation to molding. The control group was conducted with same volume of normal saline. Ten mice randomly selected were executed on the day 1, 3, 7, 14, and 21 after modeling in the two groups. Hematoxylin and eosin (HE) staining was used to observe the pathological changes of lung tissue and calculate the inflammation score and pulmonary coefficients in five mice of two groups. Alkali hydrolysis method was used to detect the content of hydroxyproline, and the bronchoalveolar lavage fluid (BALF) was collected to assess the cell counts and apoptotic levels of AM in another five mice. Results Mice of model group showed inflammatory cell infiltration and alveolar wall widening on day 3, along with an aggravate inflammation and increased inflammation score on day 7. The fibroplasia and collagen sediment were increased on day 14 and day 21. The inflammation score was decreased significantly in day 21 compared with those in day 7 and day 14. The hydroxyproline contents were increased significantly on day 21 than those on day 1, day 3 and day 7 in model group, but no significant difference when compared with those of day 14. The cell count and apoptotic rates of AM, and pulmonary coefficients showed changes of increasing first and then decreasing in model group, which reached the peak at day 7.Conclusion The cell counts and apoptotic levels increase in the preliminary stage of inflammatory and decrease in pulmonary fibrosis phase in bleomycin-induced pulmonary fibrosis model mice. These changes may play different roles in the progression of pulmonary fibrosis. Related Articles | Metrics

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The effect of Xintong Changluo complex prescription ShensuⅡ on renal interstitial fibrosis and TGF-β1 expression in FSGS rats DOU Yi-tian, LI Chong△, MA Hong-jie, ZHANG Tao 2017, 45 (3):  239-243.  doi: 10.11958/20161572 Abstract ( 774 )   PDF (1574KB) ( 3692 )   Abstract: Objective To observe and discuss the effect of the traditional Chinese drug complex prescription ShensuⅡfrom Xintong Changluo therapeutic principle on renal interstitial fibrosis (RIF) and transforming growth factor-β1 (TGF-β1)expresssion in focal segmental glomerulosclerosis (FSGS) model rats. Methods Forty- eight healthy male SD rats were randomly divided into control group (n=12) and modeling group (n=36). Rats of modeling group were injected by doxorubicin hydrochoride for FSGS model. Rats of modeling group were sub-divided into model group, benazepril group and TCM group randomly. In 12 weeks, TCM group was given by intragastric administration of ShensuⅡ (3.5 g/100 g), benazepril group was given by intragastric administration of benazepril suspension (0.33 mg/100 g), control group and model group were given by intragastric administration of same volume of saline. HE /Masson staining was used to observe changes of tubulointerstitial pathomorphology. The degree of injury and fibrosis was measured. The expressions of fibronectin (FN) and TGF- β1 were detected by immunohistochemical SP method. Results The process of renal interstitial fibrosis was slower in FSGS rats of TCM group. Renal interstitial pathological index was 1.51±0.80 in TCM group, which was lower than that of model group(2.18±0.38) and benazepril group (1.79±0.24). The index of renal interstitial fibrosis was 2.39±0.13 in TCM group, which was lower than that of model group (3.11±0.25) and benazepril group (2.80±0.41). The relative expression of FN in renal interstitial was 14.19 ± 3.06 in TCM group, which was lower than that of model group (21.25 ± 3.31) and benazepril group(18.51±2.29). The relative expression of TGF-β1 in renal interstitial was 2.64±0.21 in TCM group, which was lower than that of model group (6.02±0.12) and benazepril group (3.79±0.46). All the differences were statistically significant (P＜0.05).Conclusion Xintong Changluo complex prescription ShensuⅡcan reduce the process of renal interstitial fibrosis in FSGS model rats, which may be related with the inhibiting expression of TGF-β1. Related Articles | Metrics

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Effects of p38 MAPK inhibitor SB202190 on contents of several kinds of amino acids in hippocampus of rats with vascular dementia WANG Xue-peng1, PANG Jin-feng1,CHEN Xi2, HE Hai-tao3, PANG Xing-yi1, ZHAO Chang-fu1△ 2017, 45 (3):  244-248.  doi: 10.11958/20161361 Abstract ( 822 )   PDF (443KB) ( 3538 )   Abstract: Objective To investigate the effects of p38 MAPK inhibitor on glutamate (Glu), glutamine (Gln), taurine amino acid (Tau), glycine (Gly) and gamma aminobutyric acid (GABA) in hippocampus of rats with vascular dementia (VD).Methods Twenty- four healthy male SD rats were randomly divided into sham operation group, VD model group and inhibitor group. VD model was established by permanent ligation of bilateral carotid artery method, and the sham operation group stripping bilateral carotid artery but not ligation. Rats of the inhibitor group were injected p38 MAPK inhibitor SB202190 after the establishment of VD model. Morris water maze was used to evaluate the learning and memory function of rats. The samples of DG region of hippocampus were collected by microdialysis, and the contents of amino acids were detected. Results The learning and memory abilities were significantly better in sham operation group and p38 MAPK inhibitor group than those of VD model group. The latency time was significantly shorter in p38 MAPK group than that of VD model group. The time of locating the platform quadrant and the number of crossing the original platform were significantly higher in sham operation group and p38 MAPK inhibitor group than those of VD model group (P <0.05). Compared with sham group, the levels of Glu, Gln and Tau were significantly lower, and Gly and GABA were significantly higher, in VD group and p38 MAPK inhibitor group (P <0.05). Compared with VD group, Glu, Gln and Tau were significantly increased,Gly and GABA were significantly decreased in p38 MAPK inhibitor group (P <0.05). Conclusion p38 MAPK inhibitor has protective effect on VD hippocampal injury, which may be related to its ability to inhibit VD-induced abnormal secretion of amino acids and regulate the secretion of various amino acids. Related Articles | Metrics

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The effect of Jinqi Jiangtang tablet on expressions of IL-17 and IL-23 in kidney of diabetic rats LYU Yuan-jun1, LI Chang-ping2, TAN Xiao-feng1, LI Jin-e1, CUI Zhuang2△ 2017, 45 (3):  249-253.  doi: 10.11958/20170049 Abstract ( 1004 )   PDF (630KB) ( 4143 )   Abstract: Objective To investigate the effect of Jinqi Jiangtang tablet on the activation of T helper type 17 (Th17)and the expressions of interleukin (IL)-17 and IL-23 in kidney of diabetic rats. Methods A total of 45 male SD rats were randomly divided into normal control group (NC, n=15) and experimental group (n=30). Diabetes was induced by tail vein injection with streptozotocin (STZ, 45 mg/kg). The well-established 28 diabetic model rats were then randomly divided into diabetes group (DM, n=14) and Jinqi Jiangtang tablet administration group (Jinqi, n=14). The rats in Jinqi group were given Jinqi Jiangtang tablet solution by gavage at a single dose of 2.1 g·kg-1·d-1 for 18 weeks, while NC group and DM group were given 0.9% NaCl in the same way. All rats were sacrificed after 18 weeks. The circulating Th17 frequencies were assessed using flow cytometry. Serum IL- 17 and IL- 23 levels were measured by enzyme- linked immunosorbent assay. The pathological changes in kidney were studied by electron microscope. The expressions of IL- 17 and IL-23 in kidney were detected using immunohistochemistry. Results (1) Compared with the group NC, the circulating Th17 frequencies were significantly increased in group DM and group Jinqi. The circulating Th17 frequencies were significantly lower in group Jinqi than those in group DM. (2) Compared with the group NC, the serum IL-17 and IL-23 levels were significantly increased in group DM and group Jinqi. The serum IL-17 and IL-23 levels were significantly lower in group Jinqi than those in group DM. (3) In group DM, irregular thickening of glomerular basement membrane, fusion of epithelial cell foot processes and mesangial expansion were observed by electron microscope. The above-mentioned pathological changes were improved in the group Jinqi. (4) Compared with the group NC, the expressions of IL-17 and IL-23 in the renal cortex were significantly increased in group DM and group Jinqi, and those were significantly lower in group Jinqi than those in group DM.Conclusion The activation of Th17 and the increased expressions of IL-17 and IL-23 in kidney play a potential role in diabetic nephropathy. Jinqi Jiangtang tablet can improve diabetic nephropathy through inhibiting the activating Th17 and decreasing the expression of IL-17 and IL-23 in kidney. Related Articles | Metrics

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Effects of asymmetric dimethylarginine on apoptosis and expression of c-Jun N-terminal kinase in endothelial outgrowth cells ZHANG Fu-qing, LI Xin△, HU Ya-hui, JIAO Zhan-quan, TIAN Xiao-lin, LIU Jie 2017, 45 (3):  254-257.  doi: 10.11958/20161043 Abstract ( 800 )   PDF (1056KB) ( 3514 )   Abstract： Objective To investigate the effects of asymmetric dimethylarginine (ADMA) on apoptosis and phosphorylation of c-jun N-terminal kinase (JNK) in endothelial outgrowth cells (EOCs). Methods The mononuclear cells were harvested from umbilical cord blood by ficoll density gradient centrifugation, and induced into EOCs and then expanded in vitro. The identified EOCs were treated with different concentrations of ADMA (0, 1, 5, 10, 20 µmol/L) for 48 h.The adherent cells were treated with 10 µmol/L ADMA， then different concentrations of JNK specific inhibitor SP600125 (0，5， 10， 20 and 40 µmol /L) were added and incubated for 48 hours. Caspase-3 activity was measured by microplate reader.Apoptotic incidences of EOCs were quantitatively determined by flow cytometry. The expression of Caspase- 3 and phosphorylase- JNK (p- JNK) were detected by Western blot assay. Results The treatment of ADMA (1- 20 µmol/L)significantly induced apoptosis in EOCs by enhancing Caspase- 3 express and also induced phosphorylation of JNK (P＜0.05). Meantime, the JNK specific inhibitor SP600125 could attenuate the apoptosis induced by ADMA during this process(F=6.733， P＜0.05) and inhibit the expression of Caspase- 3 and p- JNK. Conclusion ADMA can induce apoptosis in EOC, which may be achieved by activating JNK signal transduction pathway. Related Articles | Metrics

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Correlation between low expression of miR-1301 and poor prognosis in patients with ovarian cancer GAO Hong-ye, LI Lian, ZHENG Hong△ 2017, 45 (3):  258-262.  doi: 10.11958/20170046 Abstract ( 999 )   PDF (865KB) ( 3682 )   Abstract: Objective To analyze the expression of miR-1301 and clinical significance in patients of ovarian cancer using public database, and predict the possible target genes of miR- 1301 related to the prognosis of ovarian cancer.Methods Data of ovarian cancer in the TCGA database were collated. Ovarian cancer patients were divided into two groups(low expression group and high expression group) according to the median of miR- 1301 expression. Patients were divided into two groups according to age (＜60 years vs. ≥60 years), tumor location (unilateral vs. bilateral), clinical stage (Ⅰ+Ⅱ vs.Ⅲ+Ⅳ), longest dimension of tumor (＜2 cm vs. ≥2 cm), tumor grade (G1+G2 vs. G3+G4) and residual tumor (no residue vs.residual). Chi-square test was used to analyze the difference of miR-1301 expression in different patients of ovarian cancer.Kaplan- Meier (K- M) was used to analyze the survival difference of different factors, and multivariate Cox proportional hazards regression model was used to analyze the prognostic factors of patients with ovarian cancer. The target genes of miR-1301 were predicted by bioinformatics method, and survival analysis was performed by K-M. The correlation between the expression of target gene and miR-1301 expression was analyzed by Pearson and Spearman correlation methods. Results Chi-square test showed that there was no significant difference in the expression of miR-1301 in different clinical features of ovarian cancer. K-M survival analysis and Cox regression analysis showed that miR-1301 was an independent risk factor for the prognosis of ovarian cancer. Low expression of miR-1301 was associated with poor prognosis in patients with ovarian cancer (P＜0.05). The results of bioinformatics analysis displayed that high expressions of miR-1301 target genes including PAQR5, ATP2B1, KPNA3, TSC22D3, PTRF and HS6ST3 were associated with poor prognosis. Among them, PTRF and HS6ST3 expressions were negatively correlated with expression of miR- 1301 (P＜0.05). Conclusion Low expression of miR-1301 is significantly associated with poor prognosis of patients with ovarian cancer, which may provide a new target for the prediction of prognosis of ovarian cancer. Related Articles | Metrics

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The relationship between serum uric acid and the change trend of blood pressure in adults without hypertension SONG Kun1, XU Hai-yan 2, GU Ye-qing2, SHI Hong-bin1, ZHANG Qing1, LIU Li1, MENG Ge2, NIU Kai-jun1,2? 2017, 45 (3):  263-266.  doi: 10.11958/20161147 Abstract ( 816 )   PDF (357KB) ( 4098 )   Abstract: Objective To evaluate the relationship between serum uric acid (SUA) and the long-term change trend of blood pressure (BP) in adults without hypertension. Methods The longitudinal data were collected from Tianjin Medical University, General Hospital-Health Management Centre during 2007 to 2013. The median duration of follow-up was 3.0years. A total of 26 904 participants (males, 13 596; females, 13 308) were hypertension-free at baseline. SUA concentrations were determined by the enzymatic methods. A repeated measures ANCOVA analysis was used in this study. Results Aftermultiple adjustments, in males, the variations of systolic BP (mmHg) for increasing quintiles of SUA were 1.2 (1.0, 1.4), 1.3(1.0, 1.5), 1.4 (1.2, 1.7), 1.5 (1.3, 1.8) and 1.7 (1.5, 2.0); and the variations of diastolic BP (mmHg) for increasing quintiles of SUA were 0.8 (0.6, 1.0), 1.0 (0.8, 1.1), 1.0 (0.8, 1.2), 1.2 (1.0, 1.4) and 1.4 (1.2, 1.6). Repeated ANOVA analysis showed a significant and positive correlation between SUA levels and the change of systolic BP and diastolic BP in males (Ptime × group<0.01 both in systolic BP and diastolic BP), but not in females (systolic BP: Ptime × group= 0.57; diastolic BP: Ptime × group= 0.60).Conclusion This study has demonstrated that SUA level is an independent predictor for the change of blood pressure in males, but not in females. Related Articles | Metrics

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Expression and clinical significance of induced sputum neutrophil S100 A8/A9 in children with bronchial asthma ZHOU Si-fang1△, DING Ying-ping2, WU Xin-long2, SUN Jian1, HU Xiang-yun1, DENG Huan1 2017, 45 (3):  267-270.  doi: 10.11958/20161195 Abstract ( 1152 )   PDF (345KB) ( 4341 )   Abstract: Objective To investigate the expression and clinical significance of neutrophil S100A8/A9 in induced sputum in children with bronchial asthma. Methods A total of 108 cases of bronchial asthma patients in the Fourth Affiliated Hospital of Nanchang University were involved in the study form October 2014 to October 2015. According to the severity of the disease, the patients were divided into mild group (n=40), moderate group (n=36) and severe group (n=32).Twenty health children were taken as control group at the same period. All the patients were treated with budesonide aerosol for three months, and the control group was received aerosol inhalation for normal saline (NS). The ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC, FEV1%) were used to evaluate the pulmonary function in two groups. The asthma control questionnaire (AcQ- 5) score was used to estimate the asthma control effects. The expression level of neutrophil S100A8/A9 mRNA in induced sputum was detected by real-time PCR. The correlation of S100A8/A9 mRNA, AcQ-5 score and FEV1% was analyzed. Results Before the treatment, the FEV1% decreased, while the AcQ-5 score and express level of S100A8/A9 mRNA significantly increased with the severity of disease (all P < 0.01). Three months after treatment, asthma was completely controlled in 60 patients, partial controlled in 31 cases and uncontrolled in 17 cases.With the improvement of the therapeutic efficacy, the FEV1% significantly decreased, while the express level of S100A8/A9 mRNA significantly increased (all P < 0.01). The express level of S100A8/A9 mRNA in induced sputum neutrophils wasnegatively correlated with FEV1% (r=-0.327 and -0.406 respectively, P < 0.05), which was positively correlated with ACQ-5 score (r=0.704 and 0.817, P < 0.05). Conclusion The level of S100A8/A9 expression in induced sputum neutrophil is positively correlated with the severity of asthma, which can be used as clinical indicators of the severity and the efficacy of asthma. Related Articles | Metrics

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A correlation analysis of PCSK9 level and coronary artery disease in elderly patients with acute myocardial infarction complicated with type 2 diabetes mellitus XIA Xue, ZHANG Ying-wu, QU De-tao, WANG Li△ 2017, 45 (3):  271-273.  doi: 10.11958/20161470 Abstract ( 825 )   PDF (340KB) ( 3684 )   Abstract: Objective To investigate the correlation between serum proprotein convertase subtilisin/kexin 9 (PCSK9)level and the severity of angiographic coronary artery disease (CAD) in elderly patients with acute myocardial infarction(AMI) complicated with type 2 diabetes mellitus (T2DM). Methods The patients over the same period were divided into three groups: the elderly patients with AMI and T2DM (observation group, n=46), the elderly non diabetic patients with AMI (positive control group, n=34) and patients with chronic stable coronary heart disease (negative control group, n=33). The serum PCSK9 level was detected by enzyme-linked immunosorbent (ELISA) in three groups. The correlation between serum PCSK9 level and low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), glycosylated hemoglobin (HbA1c), high sensitive C reactive protein (Hs-CRP) and Gensini score were analyzed. Results The levels of PCSK9, HbA1c, Hs-CRP and Gensini score showed a gradually increased tendency in negative control group, positive control group and observation group. Multiple comparison differences between groups were statistically significant (P < 0.05). The serum PCSK9 level was positively correlated with Hs-CRP and Gensini score in observation group (P < 0.05), and showed no correlation with HbA1c, TG, TC, LDL-C and HDL-C (P > 0.05). Conclusion The serum level of PCSK9 is positive correlated with the severity of CAD, which can be used to determine the severity of coronary artery lesions in elderly patients with AMI complicated with T2DM. Related Articles | Metrics

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Changes of PCSK9 level in patients with acute coronary syndrome and correlation analysis with LPS ZHANG Xiu-ze1, WANG Li2△ 2017, 45 (3):  274-277.  doi: 10.11958/20161329 Abstract ( 1231 )   PDF (350KB) ( 3541 )   Abstract: Objective To explore the correlation between PCSK9 and LPS or lipoprotein in patients with acute coronary syndrome (ACS). Methods A total of 126 patients with coronary artery disease confirmed by coronary angiography were selected in our hospital from December 2015 to June 2016, including 65 patients with ACS and 61 patients with stable angina (SAP). And 49 patients without coronary heart disease confirmed by coronary angiography were used as the control group. Values of high sensitivity C reactive protein (hs- CRP), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)-A1 , apo-B and fasting plasma glucose (FPG) were measured by fasting blood before radiography. Plasma PCSK9 and LPS levels were measured by enzyme-linked immunosorbent assay. Results The levels of PCSK9, LPS, hs-CRP, LDL-C, TC, apo-B and fasting blood glucose were significantly higher in ACS group than those in SAP group and control group (P < 0.05), and HDL-C was lower than that of the control group (P < 0.05). PCSK9, LPS, LDL-C and apo-B levels were higher in SAP group than those of control group. The levels of plasma PCSK9 were positively correlated with LPS, hs-CRP， LDL-C, TC and apo-B in ACS patients (r = 0.509, 0.373, 0.516, 0.479, 0.470, all P < 0.05). Conclusion Plasma PCSK9 and LPS are involved in the development of coronary atherosclerosis. PCSK9 may play an important role in the pathogenesis of ACS by participating in the inflammatory reaction and lipid metabolism. Related Articles | Metrics

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Short-term application of noisy pressure support ventilation in patients of AECOPD with respiratory failure YU Hong-zhi, WU Qi△ 2017, 45 (3):  278-281.  doi: 10.11958/20161490 Abstract ( 908 )   PDF (364KB) ( 3641 )   Abstract: Objective To investigate the effects of noisy pressure support ventilation (Noisy PSV) in patients of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with respiratory failure, and to provide basic support for the new weaning mode for AECOPD. Methods A single-center, prospective, randomized, crossover clinical research was conducted. A total of forty-six AECOPD combined with respiratory failure patients who mechanically ventilated more than 24 hours in intensive care unit (ICU) of Tianjin Haihe Hospital from November 2014 to October 2015 were enrolled in this study. When the respiratory failure improved through conventional treatment, patients were mechanically ventilated with conventional PSV and Noisy PSV for two hours respectively in random sequence during spontaneous breathing recovery phase. The pressure support (PS) level was titrated to reach tidal volumes (Vt) about 8 mL/kg in both modes. The level of positive end-expiratory pressure (PEEP) and fraction of inspired oxygen were kept unchanged in both modes. The coefficient of variation of PS during Noisy PSV was set at 30% . Data of gas exchange, hemodynamics, lung functional parameters,breathing patterns and patient-ventilator synchrony were analyzed. Results All of the patients were well tolerated with the two modes, and no adverse reactions were found. The changes of gas exchange, hemodynamics, respiratory mechanics in PSV and Noisy PSV showed a clinical acceptable range. The variability of Vt was significantly increased in Noisy PSV mode than that in conventional PSV mode. While the number of asynchrony events was decreased in Noisy PSV mode than that in conventional PSV mode. Conclusion The Noisy PSV is safe and feasible for patients of AECOPD with respiratory failure,which may be a new weaning mode for AECOPD. Related Articles | Metrics

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Effects of periodontal basic treatment on peritoneal dialysis in patients with periodontitis ZHANG Jin-wei1,2, LIU Jian-shan1, MA Ming1, HOU Xiao-yan1, GUO Le-le1, PENG Cheng1△ 2017, 45 (3):  282-284.  doi: 10.11958/20161196 Abstract ( 1013 )   PDF (317KB) ( 3854 )   Abstract: Objective To investigate the local or systemic effects of initial periodontal therapy on peritoneal dialysis in patients with chronic kidney disease and periodontitis. Methods Sixty-one patients with both periodontitis and regular peritoneal dialysis were selected in this study and were randomly divided into observation group (n=31) and control group (n=30). Patients in observation group were given periodontal initial therapy (ultrasonic supragingival scaling and ultrasonic subgingival irrigation, drug, root planing, oral health education) and peritoneal dialysis treatment. Patients in control group were given only peritoneal dialysis treatment. Clinical parameters including plaque index (PLI), gingival index (GI) and probing depth (PD) were detected before and one month after treatment in two groups. The concentrations of high-sensitivity C-reactive protein (hs-CRP) in gingival sulcus fluid and serum samples were measured by immune transmission turbidity method in two groups. Results There were no significant differences in PLI, GI, PD, hs-CRP of gingival sulcus fluid, and serum hs-CRP before treatment between the two groups. After one-month initial therapy, all the indexes were decreased in observation group, which were significantly different compared with those before treatment (P＜0.05). And all the indexes were significantly lower in observation group than those of control group. There were no significant differences in PLI, PD,GI, hs- CRP of gingival sulcus fluid, and serum hs- CRP between control group and observation group before treatment.Conclusion Periodontal initial treatment can improve the periodontal inflammation in patients with chronic kidney disease, and reduce the concentration of systemic inflammatory factor hs-CRP, decreasing the risk of infection. Related Articles | Metrics

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Risk factors of atrial fibrillation in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease LU Xiao-mao1, DI Fu-sheng1， 2△ 2017, 45 (3):  285-288.  doi: 10.11958/20161437 Abstract ( 959 )   PDF (315KB) ( 3930 )   Abstract: Objective To investigate the risk factors of atrial fibrillation (AF) in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease (NAFLD). Methods A retrospective study was conducted. A total of 153 patients with type 2 diabetes and NAFLD who were hospitalized in the department of endocrinology of Tianjin Third Central Hospital from September 2014 to March 2015 were selected. According to the results of electrocardiogram, patients were divided into AF group (n=55) and non-AF group (n=98). The clinical data were collected to compare the differences of age,gender, blood pressure, blood lipids, heart function and liver and kidney functions between the two groups. The multivariate Logistic regression was used to screen the risk factors of AF in patients with type 2 diabetes mellitus complicated with NAFLD. Results The age, body mass index (BMI), systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), gamma glutamyltransferase (GGT), uric acid (UA), B type natriuretic peptide (BNP), left atrial diameter, left ventricular hypertrophy on the electrocardiogram diagnosis rate, the neutrophil/lymphocyte ratio (NLR) and NAFLD fibrosis score (NFS) were significantly higher in AF group than those of non-AF group (P < 0.05). Multivariate Logistic analysis showed that the advanced age, left ventricular hypertrophy and high levels of TC, GGT, NLR and NFS were the risk factors for AF in patients with type 2 diabetes mellitus and NAFLD.Conclusion Inflammation and fibrosis may be the common pathological process of NAFLD and atrial fibrillation. Patients with type 2 diabetes mellitus complicated with NAFLD should control blood lipids strictly and improve the long- term chronic inflammatory state to prevent the occurrence of AF. Related Articles | Metrics

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Cone-beam computed tomography analysis of the canal shaping ability with ProTaper Universal, ProTaper Next and M3 in preparation of curved root canals WANG Tian△, LI Gui-hong 2017, 45 (3):  289-293.  doi: 10.11958/20161299 Abstract ( 1294 )   PDF (433KB) ( 3935 )   Abstract：Objective To evaluate the shaping ability of ProTaper Universal (PU), ProTaper Next (PN) and M3 in preparation of curved root canals by CBCT (cone-beam computed tomography). Methods Sixty extracted maxillary first premolars were divided into two groups according to the canal curvature:10°-25° group and 26°-75°group. Then, each group was divided into PU group, PN group and M3 group and prepared with three instruments respectively. Canals were scanned by CBCT scanner before and after preparation. The efficacy of canal preparation was analyzed. The width of dentine removed was measured at three points (2 mm, 5 mm and 8 mm to root tip). The apical transportation indexes and the centring ratio values were recorded. Results PN group and M3 group needed less time in preparation and showed more efficiency than those of PU group in 26°-75° groups. One of root canals in PU group appeared deformation, neither PN group nor M3 group appeared deformation after 5 root canal preparations in average. None instrument was broken in three groups. PU group removed more materials at internal walls than PN group and M3 group at internal walls of root canals in 5 mm from the apex.There was no difference in the offset of the external walls of root canals. Compared with the offset of the internal and external walls of root canals in 2 mm from the apex, the apical transportations prepared by the PN group were less than those of M3 group and PU group in 26°-75° groups. Compared with the offset of the internal and external walls of root canals in 5 mm from the apex, the apical transportations prepared by the PN group and M3 group were less than those of PU group, and theircentring ratio values were greater than those of PU group in 26°-75°groups. Conclusion ProTaper Next and M3 tested in this study are effective and time-saving in shaping curved root canals. The results indicate that both ProTaper Next and M3 are comparable to optimally enlarge root canal. Related Articles | Metrics

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The effects of different values of PEEP on heart index, stroke volume variation and oxygen transport index in patients monitored by FloTrac/Vigileo system SUN Zhen-tao1, WANG Ning1, SUN Xue-qing2, XIANG Dao1, CAO Ya-nan1, HAN Xue-ping1, REN Su-en3 2017, 45 (3):  294-296.  doi: 10.11958/20160785 Abstract ( 1055 )   PDF (350KB) ( 3741 )   Abstract: Objective To investigate the effects of different values of PEEP on cardiac index (CI), stroke volume nvariation (SVV) and oxygen transport index (DO2I) in patients monitored by FloTrac/Vigileo system, and to provide some references for the hemodynamic management and improvement of oxygenation for patients. Methods Sixty patients scheduled for elective television (TV) auxiliary thoracoscope radical operation for esophageal cancer were included in this study. Data of CI, SVV and DO2I were observed by the FloTrac/Vigileo system. Changes of CI, SVV and DO2I were recorded after anesthesia induction and turn left side (T0), artificial pneumothorax with 0 PEEP after 5 minutes (T1), artificial pneumothorax with 5 PEEP after 5 minutes (T2), artificial pneumothorax with 10 PEEP after 5 minutes (T3), and artificial pneumothorax with 15 PEEP after 5 minutes (T4). Results Compared with T0, CI decreased and SVV increased significantly at T1, T2, T3 and T4（P＜0.05). Compared with T1, CI decreased and SVV increased at T4. DO2I increased at T2 and T3 compared with that of T1（P＜0.05). Conclusion PEEP may have a certain influence on CI and SVV in the process of operation. The values of 5- 10 PEEP can significantly improve oxygenation and have a less influence on hemodynamics, which can be appropriately used in clinical care. Related Articles | Metrics

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Mutation analysis on DACT1 gene in children with neural tube defects in northern Chinese Han population FANG Yu-lian1, ZHAO Lin-sheng2, ZHANG Rui-ping3, ZHI Xiu-fang3, WANG Yi-zheng3, CAO Li-rong3, CAI Chun-quan4△ 2017, 45 (3):  297-300.  doi: 10.11958/20170130 Abstract ( 937 )   PDF (638KB) ( 3891 )   Abstract: Objective To investigate the correlation between neural tube defects (NTDs) and DACT1 gene, and provide the basic data for disease diagnosis and genetic counseling. Methods Blood samples were obtained from 163 NTDs patients and 480 unrelated healthy individuals. Mutation detection of DACT1 gene and DNA direct sequencing was carried out by PCR amplification. Bioinformatics analysis of these mutated loci was performed. Results Six mutations were found in NTDs patients, including 4 missense mutations (p.R45W, p.D142G, p.N356K and p.V702G). But these mutations were not found in 480 healthy individuals. Three mutated amino acid residues (p.45R, p.142D and p.356N) were highly conservative in evolution, and the mutated carriers were female patients, and suffered from anencephaly. Conclusion DACT1 gene mutation may be a risk factor of NTDs in Han population of northern China. Related Articles | Metrics

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The incidence and related factor analysis of apathy in patients with acute ischemic stroke XU Lei1, YU Ming1, TAN Hua2△ 2017, 45 (3):  301-305.  doi: 10.11958/20161357 Abstract ( 942 )   PDF (354KB) ( 4737 )   Abstract: Objective To investigate the incidence and its related factors of apathy in patients with acute ischemic stroke. Methods A total of 100 consecutive cases of ischemic stroke patients and 50 health controls were recruited in the present study. Apathy was assessed using modified apathy evaluation scale (MAES). According to the MAES score, acute ischemic stroke patients were divided into apathy group (MAES was more than 14 points) and non- apathy group. The differences of general information, clinical data, national institutes of health stroke scale (NIHSS), Montreal cognitive assessment (MoCA), Hamilton depression scale (HAMD), modified rankin scale (mRS) and the lesion location were compared between the two groups. Differences that showed statistical significance (P < 0.05) went into the multi-factor analysis. The Logistic regression analysis was used to estimate the influence factors of apathy. Results There were 34 cases of apathy in patient group (34.00%), which was significantly higher than those of control group (3 cases of apathy, 6.00%, P＜0.001). The age, incidence of diabetes, NIHSS score, HAMD score, lesions in brain stem and multiple lesions were significantly higher in apathy group than that of non-apathy group, while educational level, MoCA score were significantly lower (P < 0.05). The Logistic regression analysis showed that the higher MoCA score was a protective factor for apathy, while higher NIHSS score,lesions in brain stem and multiple lesions were risk factors for the incidence apathy. Conclusion The cognitive impairment, severity of neurological deficits, brainstem lesions and multiple lesions may be the risk factors of apathy after the occurrence of acute ischemic stroke. Related Articles | Metrics

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The relationship of expressions of ERP57 and ERAP1 and clinicopathological features in patients with breast cancer WANG Su-jie, Guzali AIKUER, HAN You-xi, WANG Yi-hai, Munira·Mushajiang△ 2017, 45 (3):  306-309.  doi: 10.11958/20160902 Abstract ( 1011 )   PDF (679KB) ( 3798 )   Abstract: Objective To observe the expressions of endoplasmic reticulum chaperone (ERP57) and endoplasmic reticulum aminopep- tidase (ERAP1) in female breast cancer, and to explore their relationship with clinical pathological parameters of breast cancer. Methods A total of 124 samples of breast cancer and 24 samples of breast fibroadenoma were collected in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2011 to December 2015. The expressions of ERP57 and ERAP1 were detected by immunohistochemistry SP method. The patients were divided into two groups according to the clinicopathological parameters. The differences of ERP57 and ERAP1 expression were analyzed between the groups. Results The positive expression rates of ERP57 were 58.8% (73/124) and 100% (24/24) in breast cancer and breast fibroadenoma samples, respectively. The difference was statistically significant (χ2=15.061, P＜0.05). The positive expression rates of ERAP1 were 47.5% (59/124) and 83.3% (20/24), and there was a difference between them (χ2= 10.328, P＜0.05). The positive expression rates of ERP57 and ERAP1 in breast cancer samples were higher in patients without axillary lymph node metastasis than those in patients with axillary lymph node metastasis; which were higher in patients with histological grade Ⅰ compared with those in patients with histological grade Ⅱ and Ⅲ; which were higher in patients with TNM stage Ⅰ-Ⅱ than those in patients with TNM stage Ⅲ-Ⅳ. There were significant differences between these groups (P＜0.05). In addition, the positive expression rate of ERAP1 in breast cancer was higher in patients more than 35 years old than those in patients under 35 years old. The positive rate of Ki67 was higher in patients ≤14% than that in patients >14%, and which was significantly higher in patient with non-triple negative than that in patients with the triple negative (P＜0.05). Conclusion The low expression levels of ERP57 and ERAP1 may play an important role in the carcinogenesis of breast cancer, and which may be valuable in judging the malignant degree and prognosis of breast cancer. Related Articles | Metrics

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The effect of preoperative pulmonary protection on surfactant protein A content in lung tissue CHI Ming-you1, WANG Xiao-dong1, LI Xin2, SUN Da-qiang2△ 2017, 45 (3):  310-313.  doi: 10.11958/20161397 Abstract ( 865 )   PDF (354KB) ( 4038 )   Abstract: Objective To explore the effect of preoperative pulmonary protection therapy on surfactant protein A(SP– A) content in lung tissue and postoperative complications. Methods Sixty patients with non- small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease(COPD) who underwent surgical treatment in Tianjin Chest Hospital from January 2015 to June 2016 were enrolled in this study. Thirty patients were included in the control group and 30 patients in the pulmonary protection group. The control group was given routine preoperative preparation, while the pulmonary protection group was given 1 week pulmonary protection therapy on the basis of routine preoperative preparation. The exhaled breath condensate (EBC) was collected and pulmonary function was re- checked after admission and before surgery. The content of SP-A in EBC was detected by ELISA. The lung tissue samples were collected during surgery, and the SP-A level was measured by Western blotting. Results The SP-A level of the pulmonary protection group was significantly higher than that of the control group (1.05±0.21 vs. 0.93±0.16, P＜0.05). The SP-A content in the preoperative EBC of the pulmonary protection group was significantly higher than that after admission［(5.51±1.48) ng/L vs. (4.99±1.32) ng/L, P＜0.01］ . After pulmonary protection treatment, the preoperative pulmonary function index was significantly higher than that after admission (P＜0.01). There was no significant difference in the incidence of postoperative pulmonary complications between two groups (23.3% vs. 43.3%, P＞0.05). The average postoperative hospital stay was statistically significant shorter in the pulmonary protection group than that in the control group［(9.2 ± 3.1) d vs. (11.6 ± 4.8) d, P＜0.05］ . ConclusionPreoperative pulmonary protection therapy can not only improve pulmonary function and shorten postoperative hospital stay,but also improve SP-A content in lung tissue. Related Articles | Metrics

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Effects of rosuvastatin therapy on short-term prognosis of myocardial infarction in patients with acute ST segment elevation WANG Dan-dan, LI Xiu, WANG Man-man, LIU Xiang-li△ 2017, 45 (3):  314-317.  doi: 10.11958/20160967 Abstract ( 1157 )   PDF (340KB) ( 3721 )   Abstract: Objective To investigate the therapeutic effects and adverse drug reactions of different doses of rosuvastatin in patients with acute ST segment elevation myocardial infarction (STEMI). Methods A total of 115 patients with STEMI were collected from Department of Cardiology, the Second Hospital of Tianjin Medical University. According to different oral doses of rosuvastatin, patients were divided into two groups including 5 mg/d rosuvastatin treatment group (lowdose group, n=44) and 10 mg/d Rosuvastatin treatment group (moderate- dose group, n=71). Patients of two groups were treated with Rosuvastatin at least 1 month after discharge. Data of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed and compared before and after treatment between two groups. The major cardiovascular adverse events (MACE) and adverse reactions were recorded in two groups of patients. Results There were no significant differences in blood lipid and liver function levels before and after one month treatment between the two groups. After one month treatment, levels of TC, LDL- C, ALT and AST were significantly decreased in both groups of patients compared with those before treatment (P＜0.05). There were no significant differences in levels of TG, and HDL-C before and after treatment between two groups. The incidence of MACE (heart failure and angina pectoris) was significantly lower in moderate-dose group than that in low-dose group (P＜0.05). There was no significant difference in the proportion of malignant arrhythmia between the moderate-dose group and the low-dose group (P＜0.05). No target vessel repair and death were found in the two groups. No obvious adverse drug reactions were found during the follow-up period. Conclusion The hypolipidemic effects are epuivalent between 5 mg/d rosuvastatin and 10 mg/d on the basis of conventional treatment for STEMI patients, but the moderate dose can reduce the incidence of MACE and improve prognosis. Related Articles | Metrics

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A case of acute tumor lysis syndrome after TACE operation for primary liver cancer LI Yang, ZHANG Ya-min△, HOU Jian-cun 2017, 45 (3):  318-319.  doi: 10.11958/20161167 Abstract ( 1070 )   PDF (361KB) ( 3938 )   Abstract: Tumor lysis syndrome (TLS) is the rapid dissolution of tumor cells and cell contents, and its metabolite is rapidly released into the blood, causing a series of complications such as high uric acid, high potassium, high phosphorus,hypocalcemia and acute renal insufficiency. TLS is commonly seen in patients with rapidly growing malignant tumors that are sensitive to chemotherapy, and which is rare in solid tumors. We found one case of primary liver cancer with acute TLS, who was given hemodialysis to protect the liver and symptomatic treatment, and the patient is on the mend. Related Articles | Metrics

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Flexible laser endotracheal intubation optical device used for oral and maxillofacial intubation operations in 42 patients LI Xin-peng△, ZHANG Ji-jun, LI Hua, WANG Shi-min 2017, 45 (3):  320-323.  doi: 10.11958/20161419 Abstract ( 1035 )   PDF (591KB) ( 3856 )   Abstract: Objective To explore the effect of flexible laser endotracheal intubation optical device (patent number 201520785723.7) on oral and maxillofacial intubation operations. Methods Forty- two patients with the oral and maxillofacial intubation optical device for general anesthesia were included in this study. The patients were from 16 to 73 years old and ASAⅠ-Ⅱ. Surface anesthesia was prepared for airway and nasal cavity. There were 27 patients whose mouth opening were smaller than 3 cm. After intravenous injection of midazolam 0.05 mg/kg and sufentanil 0.2 μg/kg, reinforced endotracheal tube was inserted into throat 13-15 cm, then the probe shape to 120° and optical device were placed into the tube respectively, guided the tube according to the light spot in front of neck. There were 15 patients whose mouth opening were not smaller than 3 cm. The quick guidance optical device and larygoscope were adopted to help the intubation. After intravenous injection of midazolam 0.05 mg/kg, sufentanil 0.5 μg/kg, propofol 2 mg/kg, cisatracurium 0.2 mg/kg, the reinforced endotracheal tube was inserted into the oral cavity nasally, and completed intubation with laryngoscope. The success rate of intubation, time of intubation, the real-time blood pressure before and after intubation, heart rate and related complications were recorded before intubation and after intubation. Results In the 42 patients, 41 patients were successful for guidance intubation, and the success rate of intubation was about 97.6%. The average intubation time was（124.5±38.2）seconds. The shortest intubation time was 12 seconds and the longest was 276 seconds. During intubation, the increases of blood pressure and heart rate were in the normal range (<30%). Levels of SpO2were maintained at 0.92-1.00. All the patients were without agitation. There were no serious complications such as hoarseness and pharyngalgia after operation.Conclusion The flexible laser endotracheal intubation optical device can be used quickly for oral and maxillofacial intubation, and the 45° bevel design for optical device can form two kinds of zones with bright light upward and downward. It is a new tool for nasal intubation that is more convenient for location of light guidance, and has high success rate and small stimulation. Related Articles | Metrics

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The progress in metabolomics in respiratory disease HU Jun, YI Gui-sheng△ 2017, 45 (3):  324-328.  doi: 10.11958/20161237 Abstract ( 829 )   PDF (373KB) ( 3789 )   Abstract: When a series of "omics" technologies such as genomics, epigenomics and proteomics are proposed, the concept of metabolomics occurs. Metabolomics is a top- down system biology approach, which analyzes endogenous metabolites by using high throughput, high resolution and high sensitivity based on metabolic analysis platform. By identifying characteristic biomarkers and analyzing the biomarkers of metabolic pathway, it will provide a new way for the diagnosis and treatment of diseases. Therefore, it is more and more widely used in bronchial asthma, chronic obstructive pulmonary disease, pulmonary cystic fibrosis, acute respiratory distress syndrome, pulmonary tuberculosis, lung cancer and other respiratory diseases. In this paper, the application of metabolome analysis in respiratory disease of recent years has been briefly reviewed. Related Articles | Metrics

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The research progress of blood transfusion therapy in traumatic brain injury SUN Jian, TIAN Ye, WANG Yi, DONG Xin-long, JIANG Rong-cai, ZHANG Jian-ning△ 2017, 45 (3):  329-332.  doi: 10.11958/20160680 Abstract ( 854 )   PDF (312KB) ( 3488 )   Abstract: Traumatic brain injury is always associated with hemorrhage and coagulopathy, leading the occurrence of anemia, platelet function inactivation, platelet and coagulation factor consumptive reduction. Theoretically, transfusion therapy should be given to supplement the missing component in an appropriate range. However, whether the transfusion therapy can improve the prognosis of patients with traumatic brain injury, and the indications of transfusion, have been the focus of academic debate for a long time. This article reviews the latest progress of transfusion therapy in traumatic brain injury, and provides reference for better guidance of transfusion in clinical treatment. Related Articles | Metrics

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The emerging landscape of circular RNAs in cardiovascular diseases Wang Yuan-yuan, Li Guang-ping△ 2017, 45 (3):  333-336.  doi: 10.11958/20161588 Abstract ( 931 )   PDF (401KB) ( 3973 )   Abstract: Circular RNA (circRNA) is a class of non- coding RNA that assumes a covalently closed continuous conformation. Recent studies have revealed that circRNAs are stable and widely expressed, and often exhibit cell typespecific or tissue-specific expressions. Emerging evidence indicates that some circRNAs can serve as microRNA (miRNA)sponges, regulate transcription or splicing, and can interact with RNA binding proteins. Moreover, circRNAs have been reported to play essential roles in myriad life processes, such as aging, insulin secretion, tissue development, atherosclerotic vascular disease, cardiac hypertrophy and cancer. Here, we review the current understanding of circRNA classification,function and significance in some cardiovascular diseases. Related Articles | Metrics