2025-03-29 2018, Volume 38 Issue 2

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  • Ping-ping Liao , Li-hua Liu , Bin Wang , Xin Fang , Shao-qiong Zhou , Wei Li , Yan-qing Zhang , Si-ming Guan

    Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA), we found that the HDAC9 mRNA expression level in NYHA grade II–III group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF), whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

  • Yan-yan Meng , Yuan Liu , Zhe-fu Hu , Yao Zhang , Jian Ni , Zhen-guo Ma , Hai-han Liao , Qing-qing Wu , Qi-zhu Tang

    The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaccharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear factor-κB (NF-κB) signaling pathways. As a result, increased mRNA expression of interleukin (IL)-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis of H9c2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.

  • Yan-xiang Cheng , Gan-tao Chen , Xiao Yang , Yan-qing Wang , Li Hong

    The objectives of this study were to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudotype virus on SiHa cytobiology behavior by cutting the HPV16 E6 gene selectively and to explore the role of this system in the treatment of cervical cancer. After designing specific gRNA sequences targeting HPV16 E6, generating hCas9-EGFP and E6-gRNA-RFP plasmids, and preparing the pseudovirus of HPV16 carrying E6-gRNA and Cas9 plasmids, we determined the titer of the pseudotype virus using the TCID50 method. We obtained the pseudotype virus of HPV16 carrying E6-gRNA and Cas9 plasmids to transfect cervical cancer SiHa cells. Experimental subjects were divided into control group, empty virus group, E6-gRNA transfected group, Cas9 transfected group and Cas9+E6-gRNA transfected group. The molecular size of the cutting sequence was detected using the T7E1 enzyme digestion method and agarose gel electrophoresis, and the cleavage function of CRISPR/Cas9 on the E6 gene was determined at the same time. RT-PCR and Western blotting were performed to detect the mRNA and protein expression levels of E6 in all the groups; the Transwell cell migration assay was performed to detect the cell migration ability and metastasis in all groups. Heterotopic transplantation tumors were incorporated into mice and were used to investigate the effects of the CRISPR/Cas9 system mediated by the HPV pseudovirus on the tumorigenic ability of SiHa cells by selectively cutting HPV16 E6. The HPV16 pseudotype virus carrying E6-gRNA and Cas9 plasmids could successfully infect SiHa cells, and there were two cutting zones in the Cas9+E6-gRNA transfected group. However, the empty virus group, E6-gRNA transfected group and Cas9 transfected group had no corresponding zone. Compared with those in the control group, the empty virus group, E6-gRNA transfected group and Cas9 transfected group, the mRNA and protein expression levels of E6 in SiHa cells were downregulated in the Cas9+E6-gRNA transfected group (P<0.01). In addition, the proliferation and migration abilities of SiHa cells were significantly inhibited (P<0.01). There were no significant differences among the other groups. In contrast to the control group, the HPV pseudotype virus carrying E6-gRNA and Cas9 plasmids could significantly delay the growth of tumor cells of the ectopic tumor transplantation model (P<0.01). The CRISPR/Cas9 system mediated by the HPV pseudotype virus to knockout E6 gene expression exhibited a clear inhibitory effect on the biological function of SiHa cells, which indicated that knocking out the E6 gene using the CRISPR/Cas9 system mediated by the HPV pseudotype virus had a potential effect of eliminating HPV infection and inhibiting the growth of HPV-related tumors. Taken together, these findings provide insight into a new treatment strategy for the prevention and treatment of hr-HPV infected disease, particularly in HPV-related tumors.

  • Yan-qiang Zhou , Yin-tao Zhao , Xiao-yan Zhao , Cui Liang , Ya-wei Xu , Ling Li , Yuan Liu , Hai-bo Yang

    Finding the novel drug from the effective components of traditional Chinese herbal medicine is a hotspot of the modern pharmacological research. Hyperoside (HYP) belongs to flavonoid glycosides, and it has various properties, such as anti-inflammation, anti-spasm, anti-diuretic, antitussive, lowering blood pressure, and lowering cholesterol effects as well as protective effects for the cardiac and cerebral blood vessels. The purpose of this study was to investigate the effects of HYP on inflammatory and apoptotic responses in vascular endothelial cells stimulated by lipopolysaccharide (LPS) and further to identify the possible mechanisms underlying these effects. In our study, human umbilical vein endothelial cells (HUVECs) were stimulated with 1 μg/mL LPS in the presence or absence of HYP (10, 20 and 50 μmol/L). Our results indicated that HYP alone exerted no cytotoxicity on HUVECs, while it had an up-regulatory effect on the viability of HUVECs induced by LPS in a dose-dependent manner; increased mRNA expression of IL-1β, IL-6, TNFα and iNOS induced by LPS was attenuated after treatment with HYP both in a dose-and time-dependent manner; LPS-induced HUVECs apoptosis and cleaved-caspase 8, 9, 3 were all significantly reduced by HYP. Furthermore, the possible pathway involved in apoptosis and inflammation by HYP was detected, and the results showed that when treated with HYP, LPS-induced mitochondrial membrane instability was significantly inhibited through up-regulation of Bcl-2 and down-regulation of Bax. Furthermore, the expression of TLR4 and the phosphorylation of IκBα and p65 in LPS-treated cells were blocked by HYP. Our results suggested that HYP treatment prevented HUVECs from LPSinduced inflammation and apoptosis responses, which might be mediated by inhibiting TLR4/NFκB pathway.

  • Tong Qiu , Yan-yan He , Xiao Zhang , Xiao-lin Ma

    The poor survival of mesenchymal stem cells (MSCs) compromises the efficacy of stem cell therapy. Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy. In this study, the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms. Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining. Signaling pathways involved in serum-deprivation induced apoptosis were analyzed using Western blotting. The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment. Serum deprivation was shown to lead to protein expression alterations in Bax, Bcl-2, casepase-3, casepase-8, GRP78, and CHOP during experiments. The data suggested that the mitochondria death pathway, the extrinsic apoptotic pathway and the endoplastic reticulum(ER) stress pathway were all involved in MSCs apoptosis. The increase in expression of CHOP and the simultaneous decrease in Bcl-2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.

  • Yu-rong Wang , Ru-tao Hong , Yuan-yuan Xie , Jian-ming Xu

    Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CCl4. The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer. Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry. Expression levels of TGF-β1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CCl4-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-β1/Smad pathway, as evidenced by decreased TGF-β1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

  • Meng-ya Zhao , La-mei Wang , Jing Liu , Xing Huang , Jing Liu , Ya-fei Zhang

    Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most prominent oncomiR, plays an important role in tumor progression. In this study, we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate. Because of the established anti-apoptosis effect of miR-21, it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis. qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased. Also, transfection of miR-21 mimics provided OE33 cells resisting to anoikis. By luciferase assays, we verified that PDCD4 and PTEN were the functional targets of miR-21. In mouse model, via tail vein injection experiment, we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern. Taken together, our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells. Targeting miR-21 may provide a novel strategy to prevent metastasis.

  • Xue Lin , Jin Li , Qiu Zhao , Jue-rong Feng , Qian Gao , Jia-yan Nie

    Ulcerative colitis (UC) is a chronic inflammatory disease and its involvement area in colon is influenced by a complex network of gene interactions. We analyzed the weighted gene co-expression networks in microarray dataset from colonic mucosa of patients with UC and identified one gene co-expression module that was highly associated with the progression of involved area in UC colon (Pearson coefficient=0.81, P<0.0001). In total, 523 hub genes in this module were found to be involved in immune system process after enrichment analysis in Gene Ontology. By the STRING and Cytoscape analysis, we observed that interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) were centered in the network of hub genes. We then detected the expression of IL-8 and MMP-9 in mucosa from left-sided colon of patients using quantitative PCR and immunofluorescence assay respectively. Both quantitative PCR and immunofluorescence assay revealed the expression levels of IL-8 and MMP-9 were significantly different among the healthy controls, left-sided colitis group and pancolitis group (P<0.05). IL-8 and MMP-9 were detected with an enhanced expression in pancolitis as compared with leftsided colitis and healthy controls, respectively (P<0.05). This study demonstrates that immune system process is indispensable in the progression of disease in colon, and identifies that IL-8 and MMP-9 play potential critical roles for the progression.

  • Shang-wei Huang , Qi Jin , Ning Zhang , Tian-you Ling , Wen-qi Pan , Chang-jian Lin , Qing-zhi Luo , Yan-xin Han , Li-qun Wu

    Variant pulmonary vein anatomy (PVA) has been reported to influence the recurrence of atrial fibrillation (AF) after radiofrequency ablation. However, the effects of PVA on AF in patients undergoing cryoballoon ablation (CBA) remain unknown. The present study aimed to examine the impact of PVA on the long-term outcome of CBA for AF. A total of 78 patients (mean age 60.7±10.9 years, 64.1% males) with symptomatic and drug-refractory paroxysmal AF were enrolled in the study. Left atrium (LA) and PVA acquired at computed tomography angiography (CTA) were reconstructed with CARTO® 3 SYSTEM. Patients were routinely evaluated by 24-hour Holter monitoring following CBA. Cox regression was used to detect the predictors of AF recurrence after CBA. The results showed abnormal PVA in 30 patients (38.5%) and 18 patients (23.1%) had left common PV (LCPV). Electrical pulmonary vein isolation was achieved in all patients. After a mean follow-up of 689.5±103.8 days, it was found that patients with abnormal PVA had similar AF recurrence rate to those with normal PVA (26.7% vs. 25.0%, P=0.54), and there was no significant difference in AF recurrence rate between LCPV patients and non-LCPV patients (33.7% vs. 23.3%, P=0.29). Cox regression analysis showed that AF duration (72.9±9.0 vs. 42.3±43.2 months, HR 1.001; 95%CI 1.003-1.014; P<0.001) and cryo-applications of right-side PVs (3.0±1.6 vs. 4.7±1.7, HR 0.661; 95% CI 0.473-0.925; P=0.016) were independent predictors of freedom from AF, but PVA was not identified as a predictor of long-term success. In conclusion, the variant PVA cannot significantly influence the long-term outcome of AF patients undergoing CBA; longer AF duration and less cryo-applications of right-side PVs are associated with higher AF recurrent rate.

  • Yi-sha Huang , Jian-bo Lai , Sheng-fa Li , Ting Wang , Ying-nan Liu , Qing-xia Zhang , Shu-yuan Zhang , Chun-han Sun , Nan Hu , Xin-zhou Zhang

    The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis, primary nephrotic syndrome or other kidney disease) that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bcl-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee’s grade III than in those with Lee’s grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.

  • Zi-li Wang , Rong-zhen He , Bin Tu , Jin-shen He , Xu Cao , Han-song Xia , Hong-liang Ba , Song Wu , Cheng Peng , Kun Xiong

    This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis, which can be done in juvenile rabbits. Passagefour bromodeoxyuridine (BrdU)-labeled ADSCs were cultured, assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability. Two-month-old, healthy male rabbits (1.2 to 1.4 kg, n=45) underwent ischemic induction and were randomly divided into five groups (group A: animal model control; group B: drilling; group C: drilling & ADSCs; group D: drilling & BMP-2; and group E: drilling & ADSCs & BMP-2). Magnetic resonance imaging (MRI), X-ray imaging, hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4, 6 and 10 weeks after treatment. Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability. Similar results were observed in the rabbits in groups C and E at weeks 6 and 10. The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P<0.01). Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P<0.05). In summary, drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

  • Zhuo-wei Lei , Shi-qiang Wu , Zhuo Zhang , Yang Han , Jun-wen Wang , Feng Li , Kai Shu

    A growing number of children and adolescents are being diagnosed as Chiari malformation type I (CM-I) for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM-I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM-I underwent surgical treatment in our department. We divided the patients into two groups: pediatric group (n=11, age <18 years) and adult group (n=73, age ≥18 years). Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis (36.4%) and developmental delay (36.4%) were more common in pediatric patients, whereas, sensory disturbance (58.9%) and motor weakness (41.1%) were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group (P<0.05). Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments (P<0.05). The total Chicago Chiari Outcome Scale (CCOS) score in pediatric patients at the last followup was significantly higher than that in adult patients (P=0.002). In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM-I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.

  • Ya-fu Tan , Li-xuan Zhan , Xiao-hui Chen , Jian-jun Guo , Chao Qin , En Xu

    It is unanimously accepted that stroke is a highly heterogeneous disorder. Different subtypes of ischemic stroke may have different risk factors, clinical features, and prognoses. The aim of this study was to evaluate the risk factors, clinical characteristics, and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment (TOAST) criteria. We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period. Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria. Patients were followed up till 30 and 90 days after stroke onset. It was found that large-artery atherosclerosis was the most frequent etiology of stroke (37.4%), and showed the highest male preponderance, the highest prevalence of previous transient ischemic attack, and the longest hospital stay among all subtypes. Small artery disease (36.4%) was associated with higher body mass index, higher plasma triglycerides, and lower plasma high-density lipoprotein cholesterol than cardioembolism. Cardioembolism (7.7%), which was particularly common in the elderly (i.e., individuals aged 65 years and older), showed the highest female preponderance, the highest prevalence of atrial fibrillation, the earliest presentation to hospital after stroke onset, the most severe symptoms on admission, the maximum complications associated with an adverse outcome, and the highest rate of stroke recurrence and mortality. Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder. Studies involving risk factors, clinical features, and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.

  • Yan Liu , Hong Wang , Chen Dong , Jie-xiong Feng , Zhi-hua Huang

    Alagille syndrome (AGS) is a multisystem disorder and caused by mutations in JAG1 or NOTCH2 gene. The diagnosis of AGS is hampered by its highly variable clinical manifestations. We performed a retrospective analysis on 16 children diagnosed as having AGS in recent five years in our hospital. Cholestasis was seen in 15 patients (93.8%), heart disease in 12 (75%), characteristic facies in 7 (43.8%), and butterfly vertebrae in 7 (43.8%). Ophthalmology examination was not performed on all the patients. Further, serum biochemical parameters were compared between AGS and 16 biliary atresia (BA) patients who were confirmed by surgery. Elevated liver enzymes were seen in all the patients. Serum total cholesterol (TC) (P=0.0007), alanine aminotransferase (ALT) (P=0.0056), aspartate aminotransferase (AST) (P=0.0114), gamma-glutamyl transferase (GGT) (P=0.035) and total bile acid (TBA) levels (P=0.042) were significantly elevated in AGS patients compared to those in BA cases. However, there were no significant differences in serum total bilirubin (TB), conjugated bilirubin (CB) and albumin (ALB) between the two groups. We identified 14 different JAG1 gene variations and 1 NOTCH2 gene mutation in 16 Chinese AGS patients. Our study suggested clinical features of AGS are highly variable and not all patients meet the classical diagnostic criteria. It was suggested that hypercholesterolaemia and significantly elevated GGT, TBA and ALT may be helpful to diagnose AGS. Genetic testing is integral in the diagnosis of AGS.

  • Ping Jiang , Shan-shan Liao , Xiao-li Lan , Fa-gang Jiang

    The clinical value of whole body positron emission tomography/computed tomography (PET/CT) as an imaging tool in diagnosis of ophthalmic tumors was investigated. The retrospective observational case series were performed on the patients with suspected ophthalmic tumors who underwent whole body PET/CT. The golden standard of diagnosis was the final pathological diagnosis or the results of long-term follow-up for patients without surgery/biopsy. PET/CT findings were compared with the golden standard. The sensitivity, specificity, accuracy and positive likelihood ratio of PET/CT in the detection of ophthalmic tumors were calculated. The clinical application of PET/CT in different types of ophthalmic tumors was evaluated. The results showed that 30 patients (18 males and 12 females) with a mean age of 43.0 years (range 4–63 years) were collected. The mean sizes of orbital tumors and intraocular tumors were 26.8 mm×17.8 mm and 11.2 mm×6.1 mm, respectively. The overall sensitivity, specificity, accuracy and positive likelihood ratio of whole body PET/CT in ophthalmic tumors were 76.5%, 71.4%, 75.0% and 2.67, and were 62.5%, 100% and 70.0% in intraocular tumors, and those were 100%, 60.0% and 84.6% in orbital tumors, respectively. PET/CT findings were applied to help make appropriate treatment options in 27 out of 30 patients (90.0%), and 12 (40.0%) patients changed the treatment strategy. False negative results in 4 cases and false positive results in 2 cases were observed in this series. It was suggested that PET/CT was an effective imaging modality in detecting, diagnosing and developing therapeutic schedule for patients with ophthalmic tumors. It was more sensitive and accurate for detecting orbital tumors than for detecting intraocular tumors.

  • You-ping Zhang , Na Liu , Kai-yan Liu , Chao Pan , Xuan Cai , Shi-qi Yang , Zhou-ping Tang , Sha-bei Xu

    Brain magnetic resonance imaging (MRI) of the elderly often reveals white matter changes (WMCs) with substantial variability across individuals. Our study was designed to explore MRI features and site-specific factors of ischemic WMCs. Clinical data of consecutive patients diagnosed with ischemic cerebral vascular disease who had undergone brain MRI were collected and analyzed. Multi-logistic regression analysis comparing patients with mild versus severe WMCs was performed to detect independent associations. Analyses of variance (ANOVAs) were used to detect regionally specific differences in lesions. We found that lesion distribution differed significantly across five cerebral areas, with lesions being predominant in the frontal lobe and parieto-occipital area. To explore WMCs risk factors, after adjusting for gender, diabetes mellitus, and hypertension, only age (P<0.01), creatinine (P=0.01), alkaline phosphatase (ALP) (P=0.01) and low-density lipoprotein cholesterol (LDL-C) (P=0.03) were found to be independently associated with severe WMCs. Age (P<0.001) was strongly associated with WMCs in the frontal lobe while hypertension was independently related to lesions in the basal ganglia (P=0.048) or infratentorial area (P=0.016). In conclusion, MRI of WMCs showed that ischemic WMCs occurred mostly in the frontal lobe and parieto-occipital area. The infratentorial area was least affected by WMCs. Typically, age-related WMCs were observed in the frontal lobes, while hypertension-related WMCs tended to occur in the basal ganglia and infratentorial area.

  • Ying Chen , Yun Zhao , Hua-Ming Wang , Qing Wang , Xi Chen , Dong-qun Xu , Tao Li , Feng Yu , Xiao-yong Wang , Jia-fa Liu

    This study aimed to assess the measurement uncertainty of a new method for determination of allura redin food by high performance liquid chromatography (HPLC). The uncertainty of mathematical model of allura red is based on Europe for Analytical Chemistry(EURACHEM) guidelines. The sources and components of uncertainty were calculated, including recovery, working solution, sample mass, final volume, response of standard solution, response of sample solution. The expanded uncertainty was 0.0024 (k=2). Uncertainty of working solution was the most significant factor contributing to the total uncertainty, accounting for 86.2%. The uncertainty of volume accounted for the minimum at 0.025%. The developed method is simple and accurate, which can be used for the determination of allura redin puffed samples.

  • Wan-li Jiang , Xiao-ping Hu , Zhi-peng Hu , Zheng Tang , Hong-bing Wu , Liang-hao Chen , Zhi-wei Wang , Ying-an Jiang

    Nosocomial infection (NI) is one of the most significant complications arising after open heart surgery, and leads to increased mortality, hospitalization time and health resource allocation. This study investigated the morbidity, mortality, and independent risk factors associated with NI following open heart surgery. We retrospectively surveyed the records of 1606 consecutive cardiovascular surgical patients to identify those that developed NI. The NI selection criteria were based on the Centers for Disease Control and Prevention (CDC) guidelines. The term NI encompasses surgical site infection (SSI), central venous catheter-related infection (CVCRI), urinary tract infection (UTI), respiratory tract infection and pneumonia (RTIP), as well as other types of infections. Of 1606 cardiovascular surgery patients, 125 developed NI (7.8%, 125/1606). The rates of NI following surgery for congenital malformation, valve replacement, and coronary artery bypass graft were 2.6% (15/587), 5.5% (26/473) and 13.6% (32/236), respectively. The NI rate following surgical repair of aortic aneurysm or dissection was 16.8% (52/310). Increased risk of NI was detected for patients with a prior preoperative stay ≥3 days (OR=2.11, 95% CI=1.39–3.20), diabetes (OR=2.00, 95%=CI 1.26–3.20), length of surgery ≥6 h (OR=2.26, 95% CI=1.47–3.47), or postoperative cerebrovascular accident (OR=4.08, 95% CI=1.79–9.29). Greater attention should be paid toward compliance with ventilator and catheter regulations in order to decrease NI morbidity and mortality following cardiovascular procedures.

  • Xiu Luo , Rui Kong , Ling-fei Liu , Jia Wang , Huai-ting Gu , Fang Hou , Ran-ran Song

    The longitudinal study sought to examine the dynamic development of cognitive skills for reading among elementary-level students in Mainland China. Two groups of students in first (n=164, mean age=6.65 years at first test) and second grade (n=202, mean age=7.73 years at first test) were followed on orthographic awareness, morphological awareness and rapid automatized naming (RAN) for two years. The children exhibited significant improvement in orthographic awareness, morphological awareness and RAN from grades 1 to 4. More importantly, to the orthographic and morphological awareness, while the children took a leap from grade 1 to 2 and grade 3 to 4, the progress developed at relatively slow rates from grade 2 to 3. In order to assure children’s development of orthographic and morphological awareness, evidence-based orthographically and morphologically enhanced instruction is needed for Chinese children in the early elementary years, especially for those at the stage from grade 2 to 3.

  • Fu-quan Jia , Yu-guang Liang , Xin-yuan Zhang , Fang-liang Luo , Yan-he Xiong , Long-long Cheng , Ji-hui Liu

    In this study, we aimed to study the pattern visual evoked potentials (P-VEPs) in two eyes with varying visual acuity in one eye and to provide an objective estimation of visual acuity by comparing P-VEPs in one and two eyes. Thirty subjects were chosen, who had one eye with an acuity of 5.0, 4.85, 4.6, 4.0, or scieropia and obstructed vision and the other eye with an acuity of 5.0, respectively. P-VEPs were detected under the large grating stimuli at 3×4 spatial frequency, moderate grating stimuli (12×16 spatial frequency) and small grating stimuli (48×64 spatial frequency). Under large grating stimuli, there was no significant difference in P100 peak latency between the groups, nor was there a significant difference between the amplitude of two eyes and the amplitude of one normal-vision eye. Under moderate and small grating stimuli, there was a significant difference in P100 peak latency between the group with both eyes having an acuity of 5.0 and the group with visual acuity below 4.0 in one eye. There was a significant difference in P100 amplitude between the group with visual acuity of 5.0 in both eyes and the group with one normal-vision eye. There was no significant difference in the amplitude of two eyes and the amplitude of one normal-vision eye between any other two groups. In forensic identification, characteristics and variability of P-VEPs in one and two eyes can be used to identify malingering or decline in visual acuity.

  • Wen-wei Gao , Yu-hong He , Lian Liu , Quan Yuan , Ya-feng Wang , Bo Zhao

    Intraoperative awareness is a very serious complication of general anesthesia. Several studies have evaluated the potential association between bispectral index (BIS) and intraoperative awareness, however, the results obtained were controversial. Therefore, we performed a meta-analysis to further assess the association between the BIS monitoring and the incidence of intraoperative awareness. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to Feb. 2017. A total of five studies with 17 432 cases and 16 749 controls were included. An odds ratio (OR) and a 95% confidence interval (CI) were calculated to examine the strength of the association. The results showed that in the overall analysis, the association between the BIS monitoring and the incidence of intraoperative awareness was not significant (OR=0.58, 95% CI= 0.22–1.58, P=0.29). A stratified analysis by comparing different anesthesia methods revealed that BIS monitoring group showed a lower incidence of intraoperative awareness in patients with intravenous anesthesia when compared with non-BIS monitoring group (OR=0.20, 95% CI=0.08–0.49, P=0.0004), whereas there was no statistically significant difference in the incidence of intraoperative awareness between BIS and non-BIS monitoring groups in patients with inhalation anesthesia (OR=1.13, 95% CI=0.56-2.26, P=0.73). In conclusion, our meta-analysis showed that BIS monitoring had no appreciable advantage in the reduction of the intraoperative awareness incidence in inhalation anesthesia, while showed a remarkable superiority in intravenous anesthesia.

  • Tang-meng Guo , Bei Cheng , Li Ke , Si-ming Guan , Ben-ling Qi , Wen-zhu Li , Bin Yang

    Coronary artery disease (CAD) is a multifactorial disease in which inflammation plays a central role. This study aimed to investigate the association of inflammatory markers such as the neutrophil to lymphocyte ratio (NLR), the Global Registry of Acute Coronary Events (GRACE) score with in-hospital mortality of elderly patients with acute myocardial infarction (AMI) in an attempt to explore the prognostic value of these indices for elderly AMI patients. One thousand consecutive CAD patients were divided into two groups based on age 60. The laboratory and clinical characteristics were assessed retrospectively by reviewing the medical records. The NLR and GRACE score were calculated. In the elderly (≥60 years), patients with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI) had significantly higher NLR than did those with unstable angina (UA) and stable angina pectoris (SAP) (P<0.01). The NLR was considerably elevated in older AMI patients compared with their younger counterparts (<60 years) (P<0.05). In elderly AMI patients, the NLR was considerably higher in the high-risk group than in both the low-risk and medium-risk groups based on the GRACE score (P<0.05 and P<0.01, respectively), and the NLR was positively correlated with the GRACE score (r=0.322, P<0.001). Either the NLR level or the GRACE score was significantly higher in the death group than in the surviving group (P<0.05). By curve receiver operator characteristic curve (ROC) analysis, the optimal cut-off levels of 9.41 for NLR and 174 for GRACE score predicted in-hospital death [ROC area under the curve (AUC) 0.771 and 0.787, respectively, P<0.001]. It was concluded that an elevated NLR is a potential predictor of in-hospital mortality in elderly patients with AMI.

  • Chun-yan Guan , Yi-lan Liu , Hui Huang , Xia Yang , Juan-juan Xu , Xin-qiao Fu , De-ying Hu , Cai-hong Lu , Zhi-guo Zhang , Juan Xu , Peng Han

    Based on the outpatient interview and literature review, the initial framework of the outpatient experience of human caring scale was formed with 9 dimensions of outpatient process. The research aim was to improve the scale by Delphi method. Sixteen experts in medical management, human caring or medical education were invited to evaluate the importance of the dimensions and items of the scale and provided some expertise via filling out the Delphi consultation questionnaires twice in the consulting round. In the first round, the recovery rate showing the experts’ positivity was 80%; the coefficient of reliability (Cr) ascertaining the authority of the evaluation was 0.92; the mean and full mark ratios responding the concentration of the evaluation were 2.88–4.94 and 6.25%–93.75% respectively; the coefficients of variation (CV) and the Kendall’s W determining the concordance of the evaluation were 5.06%–52.15% and 0.21–0.24 respectively. In the second round, the recovery rate was 93.75%; the Cr was 0.93; the mean was 3.93–4.93; the full mark ratios were 26.67%–93.33%; the Kendall’s W was 0.14–0.31, the CV was 5.25%–23.61%. Via the two-round Delphi study, the scale that included 10 dimensions and 61 items has been improved. Ten dimensions are pre-hospital medical service, guidance, registration, waiting, diagnosis & treatment, paying, inspection & assay, medicine receiving, therapy/injection/transfusion and global evaluation. It was concluded that Chinese scholars have paid high attention to human caring and outpatient experience. The experts have given high agreements about the dimensions which were established with Chinese outpatient process. The dimensions are different from the similar researches about outpatient experience study. In the future, it is necessary to survey the outpatients to test the construct validity, internal consistency reliability and others of the scale to improve the scale.

  • Qiao-yuan Yan , Fei Xiang , Xiao-xu Shi , Qin Zhu

    The implementation of knowledge management (KM) in hospitals affects efficiency and outcomes of hospitals. However, few studies explored the implementation of KM in China. Twenty-two questions were designed concerning KM implementation status in over 50 hospitals. In order to understand the KM level and attitude to KM of the hospital’s managers, a random sampling survey was conducted among 138 managers from 50 different scales of hospitals in 15 provinces of China. The survey showed that overall level of KM implementation in Chinese hospitals was still low and differed among different scales of hospitals (P<0.05, or P<0.01). In all the hospitals investigated, 63.8% did not implement KM yet, among which 46% even had not planned for that. 49.8% of the hospitals investigated had no training program about KM ever and the main source of hospital staff to get knowledge was internet. It suggested that hospital managers should make much more efforts to get to know and understand theories on KM, so that hospital KM could be promoted more rapidly.

  • Xiao-ping Zhang , Wei Zeng , Hui Liu , Liang Tang , Qing-yun Wang , Zhi-peng Cheng , Ying-ying Wu , Bei Hu , Wei Shi , Yu Hu

    This study aimed to explore the mechanism of a novel mutation (p.Lys38Glu) in apolipoprotein H (APOH) gene causing hereditary beta2-glycoprotein I (β2GPI) deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant (LA) was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C (PC), protein S (PS), antithrombin (AT) and thrombomodulin (TM) was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant (c.112A>G) APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrombin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence of p.Lys38Glu mutation in APOH gene and LA in plasma.

  • Ying Song , Jin-zhi He , Ren-ke Wang , Jing-zhi Ma , Ling Zou

    The original version of this article unfortunately contained a mistake. One grant number is missing. The corrected one is given below.

    *This project was supported by grants from the National Natural Science Foundation of China (No. 81570974 and No. 81641035) and the Key Project of the Science and Technology Department of Sichuan Province (No. 2015JY0260).