2025-03-29 2015, Volume 35 Issue 6

  • Select all
  • Yan-mei Zhou , Xiao-ling Yin , Zhi-bin Huang , Yong-hua He , Li-ru Qiu , Jian-Hua Zhou

    Recent report on epidemiology of acute kidney injury (AKI) is lacking for Chinese children. We aimed to investigate the risk factors for stage and prognostic factors for renal recovery in hospitalized children. Pediatric patients (≤18 years old) admitted during 2003 to 2013 were enrolled in this study. AKI was defined and staged using Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression analysis was performed to determine the risk factors and prognostic factors. The morbidity of pediatric AKI was 0.31% (205/65 237). There were 45 (22.0%) cases in stage III, 30 (14.6%) cases in stage II and 130 (63.4%) cases in stage III. The majority of etiologies were intrinsic renal defects (85.4%). Age, weight, vomit, etiology, blood urea nitrogen (BUN) at admission and several blood gas measurements were associated with AKI stage III. Age (OR=0.894; 95% CI, 0.832–0.962; P=0.003), vomit (OR=2.375; 95% CI, 1.058–5.333; P=0.036) and BUN at admission (OR=1.135; 95% CI, 1.085–1.187; P<0.001) were identified as independent risk factors for AKI stage III. After treatment, 172 (83.9%) patients achieved complete or partial recovery. The mortality was 3.9%. Variables were found as prognostic factors for renal recovery, such as age, stage, hospital stay, BUN at discharge, white blood cells, red blood cells, platelets (PLTs), blood pH and urine blood. Among them, AKI stage (stage III vs. stage I; OR, 6.506; 95% CI, 1.640–25.816; P=0.008), BUN at discharge (OR, 0.918; 95% CI, 0.856–0.984; P=0.016) and PLTs (OR, 1.007; 95% CI, 1.001–1.013; P=0.027) were identified as independent prognostic factors. AKI is still common in Chinese hospitalized children. Identified risk factors and prognostic factors provide guiding information for clinical management of AKI.

  • Qi-jun Chen , Zhi-qiang He , Yan Yang , Yu-shun Zhang , Xing-lin Chen , Hong-ji Yang , Shi-kai Zhu , Ping-yong Zhong , Chong Yang , He-shui Wu

    Pancreaticoduodenectomy (PD) is the most effective treatment for patients with pancreatic head or periampullary lesions. Two major strategies exist: pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). However, it is yet unclear regarding the morbidity after PPPD and PRPD. This study analyzed the morbidity after PPPD and PRPD to determine the optimal surgical treatment of masses in the pancreatic head or periampullary region. A systematic search of databases identifying randomized controlled trials (RCTs) from the Cochrane Library, PubMed, EMBASE and Web of Science was performed. Outcome was compared by postoperative morbidity including overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and delayed gastric emptying (DGE) rate between PPPD and PRPD. The DGE rate in the PRPD subgroups (conventional PD [CPD] and subtotal stomach-preserving PD [SSPPD], respectively) was also analyzed. The results showed that 9 RCTs including 722 participants were included for meta-analysis. Among these RCTs, 7 manuscripts described PRPD as CPD, and 2 manuscripts described PRPD as SSPPD. There were no significant differences in the overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, or biliary leakage between PPPD and PRPD. There was a lower rate of DGE with PRPD than that with PPPD (RR=2.15, P=0.03, 95% CI, 1.09–4.23). Further subgroup analysis indicated a comparable DGE rate for the CPD but a lower DGE rate for the SSPPD group than the PPPD group. However, the result did not indicate any difference between CPD and SSPPD regarding the DGE rate (P=0.92). It is suggested that PPPD is comparable to PRPD in overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding and biliary leakage. The current data are not sufficient to draw a conclusion regarding which surgical procedure is associated with a lower postoperative DGE rate. Our conclusions were limited by the available data. Further evaluations of RCTs are needed.

  • Rong Hu , Ying-xue Li , Hai-hong Di , Zhi-wei Li , Chun-hua Zhang , Xian-ping Shen , Jun-feng Zhu , Wei-rong Yan

    The prevalence of hypertensive disorders in China was much higher than that in the United States. Considering the large population with wide geographic area of China, we aimed to add more information regarding the risk factors for hypertensive disorders of pregnancy. A case-control study was performed on 373 hypertensive cases and 507 normotensive controls. Participants were recruited from 2008 to 2014 in Yichang Maternal and Child Health Care Center in Hubei province and Anyang Maternal and Child Health Care Hospital in Henan province, China. Socio-demographic factors, family- related factors, pregnancy-associated factors, factors related to daily life behaviors and psychosocial factors were investigated with respect to hypertensive disorders in pregnancy through well-designed questionnaire. Chi-square test, t-test, univariate logistic regression analysis, and multivariate logistic regression analysis were used to find the possible risk factors behind hypertensive disorders in pregnancy. The results showed that family history of cardiovascular diseases (OR=6.18, 95% CI, 2.37 to 16.14), history of pregnancy-induced hypertension (OR=16.64, 95% CI, 5.74 to 48.22), low maternal educational level (OR=2.81, 95% CI, 1.30 to 6.04), and poor relationship with their parents-in-law (OR=3.44, 95% CI, 1.55 to 7.59) had statistically significant associations with hypertensive disorders in pregnancy through multivariate logistic regression analysis. Increased maternal age, increased pre-pregnancy body mass index, living in rural area, low paternal education level, family history of hypertension, passive smoking one year before and/or in pregnancy, and poor sleeping quality were significantly associated with hypertensive disorders in pregnancy from univariate logistic regression analysis while the associations became uncertain when they were entered for multivariate logistic regression analysis. It was concluded that family history of cardiovascular diseases, history of pregnancy-induced hypertension, low maternal educational level, and poor relationship with their parents-in-law were independent risk factors for hypertensive disorders among Chinese pregnant women.

  • Gang Chen , Ting-ting Qiao , Hao Ding , Chen-xi Li , Hui-ling Zheng , Xiao-ling Chen , Shao-ming Hu , Shi-ying Yu

    Chinese herbal medicine (CHM), as the largest application category of traditional Chinese medicine (TCM), is widely accepted among cancer patients in China. Herbal slice (HS) and Chinese patent drug (CPD) are commonly used CHM in China. This study aimed to investigate the utilization of CHM among clinicians and cancer patients in central China. Five hundred and twenty-five patients and 165 clinicians in 35 comprehensive hospitals in central China were asked to complete an anonymous questionnaire that was designed to evaluate the use of CHM. The results showed that 90.74% clinicians and 72.24% cancer patients used CHM during cancer treatment. The educational backgrounds of the clinicians and the age, education level, annual income, and cancer stage of the cancer patients were related to use of CHM. More than 90% clinicians and cancer patients had used CPD. Comparatively, the percentage of HS use was 10% lower than that of CPD use among clinicians and cancer patients. More clinicians preferred to use CHM after surgery than cancer patients did (20.41% vs. 5.37%). Enhancing physical fitness and improving performance status were regarded as the most potential effect of CHM on cancer treatment (85.71% among clinicians and 94.07% among cancer patients), in comparison with directly killing tumor cells (24.49% among clinicians and 31.36% among patients). As for refusal reasons, imprecise efficacy was the unanimous (100%) reason for clinicians’ rejection of CHM, and 95.58% patients objected to using CHM also for this reason. Furthermore, the side effects of CHM were more concerned by clinicians than by patients (33.33% vs. 15.81%). In conclusion, our survey revealed that CHM was popularly accepted by clinicians and cancer patients in central China. The reasons of use and rejection of CHM were different between clinicians and cancer patients.

  • Wei Lu , Qian Bian , Yan-yan Song , Jia-yi Ren , Xiao-ying Xu , Min Zhao

    Anxiety, depression, and even suicidal ideation are becoming the most common mental health problems affecting Chinese college students. The present study investigated the prevalence of mental health problems and their predictors in a sample of 1048 Chinese college freshmen from Shanghai. We used following brief screening instruments to measure symptoms of anxiety and depression, as well as self-control and suicidal ideation: the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder scale (GAD-7), a mental health and mental health knowledge questionnaire (MK), a mental disease-related attitude questionnaire (MA), questionnaires about the knowledge of psychological services and utilities, the Mini International Neuropsychiatric Interview (MINI) Suicide module, the Self-Rated Health Measurement Scale (SFHMS), the Self-Esteem Scale (SES), the Simplified Coping Style Questionnaire (SCQ), and the Perceived Stress Scale-10 (PSS-10). Over half of the students suffered from at least one mental health problem. Approximately 65.55% of freshmen had depression, and 46.85% had anxiety. Minority status, low family income, and religious belief were significantly associated with current mental health problems. These findings indicate that mental disorders are highly prevalent among the freshman student population. The prevalence of such mental disorders was greater than that of the general population, and the majority of students with mental health problems require treatment.

  • Mei Lin , Hua-peng Yu

    The aim of this study was to explore the effect of IL-29 on the progression of airway allergic disease by detecting the level of IL-29 in airway allergic cell models stimulated by house dust mite (HDM) in the presence or absence of dexamethasone (DEX). The same batch of human bronchial epithelial cells in exponential growth phase was randomly divided into five groups: blank group (A), 300 ng/mL HDM group (B), 1000 ng/mL HDM group (C), 3000 ng/mL HDM group (D), and 300 ng/mL HDM+100 ng/mL DEX group (E). The IL-29 mRNA expression was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The IL-29 protein expression in cell suspension was detected by ELISA. The results showed that after stimulation with HDM for 24 h, the expression of IL-29 was increased significantly, and after co-stimulation with HDM and DEX for 24 h, the expression of IL-29 in group E was significantly lower than that in the groups stimulated by HDM alone but higher than that in the group A. The differences between the different groups were significant (F=132.957, P<0.01). Additionally, the higher the concentration of HDM was, the more significant the increase in the IL-29 expression was. In conclusion, IL-29 may play a role in the progression of airway allergic disease including asthma.

  • Hong-mei Liu , Li-jun Ma , Ji-zhen Wu , Yu-guang Li

    Bone marrow mesenchymal stem cells (MSCs) transplantation could repair injury tissue, but no study confirms whether MSCs can promote the proliferation of endogenous lung stem cells to repair alveolar epithelial cells of mice with chronic obstructive pulmonary disease (COPD). This study was designed to investigate the effect of MSCs on the proliferation of endogenous lung stem cells in COPD mice to confirm the repair mechanism of MSCs. The mice were divided into control group, COPD group, and COPD+MSCs group. The following indexes were detected: HE staining of lung tissue, the mean linear intercept (MLI) and alveolar destructive index (DI), the total cell number in bronchoalveolar lavage fluid (BALF), pulmonary function, alveolar wall apoptosis index (AI) and proliferation index (PI), the number of CD45-/CD31-/Sca-1+ cells by flow cytometry (FCM), and the number of bronchoalveolar stem cells (BASCs) in bronchoalveolar duct junction (BADJ) by immunofluorescence. As compared with control group, the number of inflammatory cells in lung tissue was increased, alveolar septa was destroyed and the emphysema-like changes were seen, and the changes of lung function were in line with COPD in COPD group; AI of alveolar wall was significantly increased and PI significantly decreased in COPD group. There was no significant difference in the number of CD45-/CD31-/Sca-1+ cells and BASCs between control group and COPD group. As compared with COPD group, the number of inflammatory cells in BALF was decreased, the number of CD45-/CD31-/Sca-1+ cells and BASCs was increased, AI of alveolar wall was decreased and PI was increased, and emphysema-like changes were relieved in COPD+MSCs group. These findings suggested that MSCs transplantation can relieve lung injury by promoting proliferation of endogenous lung stem cells in the cigarette smoke-induced COPD mice.

  • Yan-hong Wei , He-xiao Tang , Yong-de Liao , Sheng-ling Fu , Li-qiang Xu , Guang Chen , Chao Zhang , Sheng Ju , Zhao-guo Liu , Liang-kun You , Li Yu , Sheng Zhou

    The type 1 insulin-like growth factor receptor (IGF-1R) and its downstream signaling components have been increasingly recognized to drive the development of malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the effects of IGF-1R and its inhibitor, AG1024, on the progression of lung cancer. Tissue microarray and immunohistochemistry were employed to detect the expressions of IGF-1 and IGF-1R in NSCLC tissues (n=198). Western blotting was used to determine the expressions of IGF-1 and phosphorylated IGF-1R (p-IGF-1R) in A549 human lung carcinoma cells, and MTT assay to measure cell proliferation. Additionally, the expressions of IGF-1, p-IGF-1R and IGF-1R in a mouse model of lung cancer were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), respectively. The results showed that IGF-1 and IGF-1R were overexpressed in NSCLC tissues. The expression levels of IGF-1 and p-IGF-1R were significantly increased in A549 cells treated with IGF-1 as compared to those treated with IGF-1+AG1024 or untreated cells. In the presence of IGF-1, the proliferation of A549 cells was significantly increased. The progression of lung cancer in mice treated with IGF-1 was significantly increased as compared to the group treated with IGF-1+AG1024 or the control group, with the same trend mirrored in IGF-1/p-IGF-1R/IGF-1R at the protein and/or mRNA levels. It was concluded that IGF-1 and IGF inhibitor AG1024 promotes lung cancer progression.

  • Jun Xiao , Qi-xian Wang , You-qing Zhu

    MicroRNAs (miRNAs) play important roles in carcinogenesis, but the global miRNA expression profile in gastric stromal tumor tissues remains unclear. This study was to examine the miRNA expression profile in gastric stromal tumor tissues and explore the function of dysregulated miRNAs by performing gene ontology (GO) and pathway enrichment analysis. Total RNA was extracted and purified from 3 pairs of frozen gastric stromal tumor tissues and the adjacent non-tumor tissues by using mirVana™ miRNA isolation kit. The miRNA expression was analyzed with Affymetrix microarrays (version 4.0) containing 2578 human mature microRNA probes. The dysregulated microRNAs were validated by quantitative RT-PCR in 30 pairs of gastric stromal tumor tissues. The target gene of the dysregulated microRNAs was predicted by miRanda, TargetScan and PicTar. GO and pathway enrichment analysis was conducted to examine the potential function of miR-3178 and miR-193a-5p. The results showed that there were 12 differently expressed microRNAs in gastric stromal tumor tissues, among which 10 miRNAs were down-regulated, and 2 were up-regulated (P<0.05). The validation results by RT-PCR were in accordance with those by microRNA microarry. GO analysis found that the target genes of miR-3178 were involved in 5 GO terms and those of miR-193a-5p in 7 GO terms in level 2. Pathway enrichment analysis suggested that miR-3178 and miR-193a-5p were related to 57 and 122 signaling pathways, respectively. It was concluded that gastric stromal tumor displays a unique miRNA signature. This specific expression may become a new diagnostic and prognostic biomarker for gastric stromal tumor. miR-3178 and miR-193a-5p function as suppressive microRNAs, and they may also become diagnosis and treatment targets for gastric stromal tumor.

  • Yue Chen , Hui-qing Yin , Hao-ling Liu , Lei Xiu , Xiao-yu Peng

    The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups: control group, non-diabetic obese group and type 2 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression patterns of hepcidin, interleukin-6 (IL-6), hypoxia-inducible factor (HIF) and ferroportin (Fpn) in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further analyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly (P<0.001). However, there was no significant difference in soluble transferring receptor (sTfR):ferritin ratio among the three groups (P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group (P<0.001). The expression levels of hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal expression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron release from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.

  • Yuan-hong Liang , Lie Liu , Dong-li Chen , Chun-ying Lin , Hong-wen Fei , Si-lin Chen , Shu-lin Wu

    Lead placement for ventricular pacing variably impacts the physiological benefit of the patient. This study evaluated the ventricular lead performance and safety of right ventricular outflow tract septal pacing in patients with bradyarrhythmia in South China over 60-month follow-up. Totally, 192 patients (108 males, and 84 females, 63±21 years old) with bradyarrhythmia were randomly divided into two groups. The right ventricular outflow tract septum (RVOTs) group had lead placement near the septum (n=97), while the right ventricular apex (RVA) group had a traditional apical placement (n=95). RV septal lead positioning was achieved with a specialized stylet and confirmed using fluoroscopic projection. All patients were followed up for 60 months. Follow-up assessment included stimulation threshold, R-wave sensing, lead impedance and lead complications. The time of electrode implantation in both the ROVTs and RVA groups were significantly different (4.29±0.61 vs. 2.16±0.22 min; P=0.009). No differences were identified in threshold, impedance or R-wave sensing between the two groups at 1st, 12th, 36th and 60th month during the follow-up period. No occurrence of electrode displacement, increased pacing threshold or inadequate sensing was found. The long-term active fixation ventricular electrode performance in RVOTs group was similar to that in RVA group. RVOTs pacing near the septum using active fixation electrodes may provide stability during long-term follow-up period.

  • Jing Hong , Jin-ping Zhang , Ling-ting Xie , Yi-fan He , Yan-yu Lv , Hong Jiang , Xiao-yan Xing

    This study was aimed to investigate clinical features of Chinese metabolic syndrome (MS) subjects with normal urinary albumin to creatinine ratio (UACR) and to estimate independent correlation factor for UACR. Data were drawn from a cross-sectional survey in participants having MS. The patients with different grade of albuminuria were divided into 4 groups according to the value of UACR (<10, 10–20, 21–30, >30 mg/g). All underwent biochemical tests. Bioelectrical impedance body fat content, islet β-cell function and insulin sensitivity were measured. Multivariable linear regression models were applied to further determine association between UACR and clinical factors with adjustment. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, fat mass, fat content and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly higher in the group with UACR at 10–20 mg/g than those in the group with UACA lower than 10 mg/g (P<0.05). Multivariable linear regression showed that TG, HbA1c, waist-hip ratio (WHR) and SBP were independently associated with UACR. The patients with normal UACR had abnormal levels of MS components. The factors independently associated with UACR were TG, HbA1c, WHR and SBP.

  • Xiang-dong Liu , Zhen-yong Chen , Peng Yang , Wen-guang Huang , Chun-fang Jiang

    The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all P<0.01). Splenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all P<0.01). The results of this study suggest that severe thermal injury damages the intestinal mucosal barrier. Splenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.

  • Min Wang , Mei-yuan Chen , Xing-jun Guo , Jian-xin Jiang

    The expression levels of hypoxia-inducible factor 1alpha (HIF-1α) and HIF-2α in pancreatic cancer (PC) and their association with clinicopathologic characteristics were investigated in order to elucidate their roles in the development of PC. HIF-1α and HIF-2α mRNA levels in 20 patients with PC were detected by quantitative real-time polymerase chain reaction. The expression of HIF-1α and HIF-2α protein in samples from other 90 patients with PC was measured by immunohistochemistry. Correlations between the expression of HIF-1α or HIF-2α and clinicopathologica features and prognosis were analyzed. The expression of both HIF-1α and HIF-2α mRNA was up-regulated in most cancer tissues (P<0.05). HIF-1α staining was weakly positive in most cancer tissues and strongly positive in adjacent pancreas tissues (P<0.05). Clinicopathologic analysis revealed that relatively strong HIF-1α expression in cancer tissues was related to greater invasion (P<0.05), higher tumor pathologic stage (P<0.05), higher American Joint Committee on Cancer (AJCC) stage (P<0.05) and shorter overall survival time (P<0.05). Conversely, HIF-2α staining was strongly positive in most cancer tissues and weakly positive in adjacent pancreas tissues. Clinicopathologic analysis revealed that relatively strong HIF-2α expression in cancer tissues was related to less invasion (P<0.05), lower tumor pathologic stage (P<0.05), lower AJCC stage (P<0.05) and longer overall survival time (P<0.05). Moreover, the HIF-1αhigh/HIF-2αlow group showed a shorter survival time than the HIF-1αlow/HIF-2αhigh group. In conclusion, although HIF-1α and HIF-2α mRNA expression patterns are the same, their protein expression patterns are significantly different and they play different roles in PC. Combined analysis of HIF-1α and HIF-2α expression might be useful to predict the prognosis of patients with PC.

  • Xin Fang , Ren-shi Xu

    Recently, several studies showed that gastrointestinal tract may be associated with pathophysiology of Parkinson’s disease (PD). Intestine tight junction protein zonula occluden-1 (ZO-1) is an important component of intestinal barrier which can be degraded by matrix metallopeptidase 9 (MMP-9). In our previous study, a significant decline in ZO-1 was observed along with enhanced MMP-9 activity in the duodenum and distal colon of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. In this study, the protective effect of simvastatin on ZO-1 was investigated using an MPTP mouse model of PD. Seven days after the end of MPTP application, the expression level of ZO-1 was evaluated by immunohistochemistry. The protein expression levels of ZO-1 and MMP9 were detected by Western blotting. Meanwhile, MMP-9 activity was analyzed by gelatin zymography. MPTP treatment led to a decrease in the expression of ZO-1, which was accompanied by elevated MMP-9 activity. Treatment with simvastatin could partly reverse the MPTP-induced changes in ZO-1 expression and reduce MMP-9 protein and activity. Taken together, these findings suggest that simvastatin administration may partially reverse the impairment of ZO-1 induced by MPTP via inhibiting the activity of MMP9, fortify the impaired intestinal barrier and limit gut-derived toxins that pass across the intestinal barrier.

  • Bin Mei , Guang-zhi Liu , Yang Yang , Yu-min Liu , Jiang-hui Cao , Jun-jian Zhang

    Based on the recently proposed Chinese ischemic stroke subclassification (CISS) system, intracranial branch atheromatous disease (BAD) is divided into large artery atherosclerosis (LAA) and penetrating artery disease (PAD). In the current retrospective analysis, we compared the general characteristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system: BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was: 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Diabetes mellitus affected more non-BAD-LAA patients than BAD-LAA patients (P=0.035). In comparison with non-BAD-PAD, patients with BAD-PAD were younger (P=0.040), had higher initial NIHSS score (P<0.001) and morbidity of ischemic heart disease (P=0.033). Within patients with BAD, the PAD subtype was associated with smoking (OR=0.043; P=0.011), higher low-density lipoprotein (OR=5.339; P=0.029), ischemic heart disease (OR=9.383; P=0.047) and diabetes mellitus (OR=12.59; P=0.020). It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general characteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD subtypes of BAD and non-BAD were revealed.

  • Hua Wang , Hong-bing Cai , Lou-lou Chen , Wen-jun Zhao , Pan Li , Zhi-qiang Wang , Zhen Li

    Cancer stem cells (CSCs) are considered responsible for the high recurrence rate in cervical carcinoma. It has been demonstrated that the signal transducer and activator of transcription 3 (STAT3) is involved in the oncogenesis and takes part in mediating the effects of maintaining stem cell phenotype and pluripotency by regulating the expression of stem cell-related transcription factors. However, the correlation between STAT3 and stem cell-related transcription factors in cervical cancer has not been elucidated. In this study, we established overexpressing plasmid (GV316-STAT3) and siRNA-STAT3 for transfecting Siha cells. Cells negative or positive for Nanog, Oct4, or Sox2 were selected by flow cytometry. Proliferation and differentiation rate of Siha cells was determined by detecting the efficiency of tumor sphere formation. The expression of Nanog, Oct4 and Sox2 (cancer stem cell markers) and STAT3 was detected by quantitative real-time PCR and immunoblotting for Siha cells and by immunohistochemistry (IHC) for cervical tissues, respectively. The results showed that Nanog+, Oct4+, and Sox2+ Siha-STAT3 over-expressing cells displayed the typical non-adherent spheres. The sphere formation efficiency was significantly different between Siha-STAT3 overexpressing cells and siRNA-STAT3 cells (P<0.05). Meanwhile, the expression levels of Oct4, Nanog and Sox2 mRNA and protein were significantly higher in Siha-STAT3 overexprssing cells than in siRNA-STAT3 cells (P<0.05). In addition, the positive rate of STAT3, Nanog, Oct4 and Sox2 in cervical cancer tissues was higher than that in chronic cervicitis group (P<0.05). There was a significantly positive relationship between STAT3 and Nanog or Oct4 or Sox2 expression (all P<0.001). These results suggested that Oct4+, Sox2+, and Nanog+ cell population possesses stem cell properties in cervical cancer, which may contribute to cervical carcinogenesis and be regulated by STAT3.

  • Xing Gu , Qin Liu , Ning Yang , Jian-fang Shen , Xue-gang Zhang , Fang Cao , Hou-zhong Ding

    Zinc finger of the cerebellum (ZIC1), one of ZIC family genes, has been shown to play important roles in many cancers such as gastric cancer and breast cancer. However, there is little known about the expression and significance of ZIC1 in endometrial cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of ZIC1 in endometrial cancer. The mRNA and protein expression of ZIC1 in endometrial cancer tissues was detected using the reversetranscription polymerase chain reaction and Western blotting, respectively. Immunostaining of ZIC1 in 99 endometrial cancer samples was examined and its associations with clinicopathological parameters were analyzed. Hec-1-B cells were transfected with ZIC1-shRNA or sc-shRNA, and cell proliferation was assayed. Hec-1-B cells stably transfected with ZIC1-shRNA or sc-shRNA were subcutaneously inoculated into nude mice, and the tumor weight was measured. A significantly increased expression of ZIC1 mRNA and protein was observed in endometrial cancer tissues compared to that in normal endometrial tissues (P<0.05). Immunohistochemical analysis showed that strong cytoplasmic immunostaining of ZIC1 was observed in almost all endometrial cancer samples (90/99) while light and moderate immunostaining of ZIC1 was only detected in 17 of 30 (56.7%) normal tissues. Moreover, up-regulation of ZIC1 was significantly correlated with age, disease stage, TNM stage and FIGO stage (P<0.05). The down-regulated expression of ZIC1 contributed to the inhibition of cell proliferation, and inhibited the growth of tumor. It was concluded that ZIC1 is over-expressed in endometrial cancer tissue but not in normal tissue, and positively correlated to the malignant biological behavior of endometrial carcinogenesis.

  • Sheng-juan Jin , Yan Liu , Shi-hua Deng , Tu-lian Lin , Abid Rashid , Li-hong Liao , Qin Ning , Xiao-ping Luo

    Activated protein C (APC), a natural anticoagulant, has been reported to exert direct vasculoprotective, neural protective, anti-inflammatory, and proneurogenic activities in the central nervous system. This study was aimed to explore the neuroprotective effects and potential mechanisms of APC on the neurovascular unit of neonatal rats with intrauterine infection-induced white matter injury. Intraperitoneal injection of 300 μg/kg lipopolysaccharide (LPS) was administered consecutively to pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish the rat model of intrauterine infection- induced white matter injury. Control rats were injected with an equivalent amount of sterile saline on the same time. APC at the dosage of 0.2 mg/kg was intraperitoneally injected to neonatal rats immediately after birth. Brain tissues were collected at postnatal day 7 and stained with hematoxylin and eosin (H&E). Immunohistochemistry was used to evaluate myelin basic protein (MBP) expression in the periventricular white matter region. Blood-brain barrier (BBB) permeability and brain water content were measured using Evens Blue dye and wet/dry weight method. Double immunofluorescence staining and real-time quantitative PCR were performed to detect microglial activation and the expression of protease activated receptor 1 (PAR1). Typical pathological changes of white matter injury were observed in rat brains exposed to LPS, and MBP expression in the periventricular region was significantly decreased. BBB was disrupted and the brain water content was increased. Microglia were largely activated and the mRNA and protein levels of PAR1 were elevated. APC administration ameliorated the pathological lesions of the white matter and increased MBP expression. BBB permeability and brain water content were reduced. Microglia activation was inhibited and the PAR1 mRNA and protein expression levels were both down-regulated. Our results suggested that APC exerted neuroprotective effects on multiple components of the neurovascular unit in neonatal rats with intrauterine infection- induced white matter injury, and the underlying mechanisms might involve decreased expression of PAR1.

  • Chun-li Xu , You-hua Hao , Yin-ping Lu , Zong-sheng Tang , Xue-cheng Yang , Jun Wu , Xin Zheng , Bao-ju Wang , Jia Liu , Dong-liang Yang

    Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure (ACLF). Toll-like receptors (TLRs) have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was to characterize the TLR4 expression in peripheral blood mononuclear cells (PBMCs) of ACLF patients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected (CHB) patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 expression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was analyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expression of TLR4 on CD4+ and CD8+ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4+ and CD8+ T cells were positively correlated with serum total bilirubin (TBIL), direct bilirubin (DBIL), international normalized ratio (INR) levels and white blood cells (WBCs), and negatively correlated with serum albumin (ALB) levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4+ T cells, which was also positively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.

  • Zhao Liu , Nian Ma , Yan Zhong , Zhan-qiu Yang

    Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus (CV) and respiratory syncytial virus (RSV). However, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin (an ingredient of Rheum palmatum) against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum palmatum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication inhibition, virucidal and anti-absorption effects, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tet-razolium bromide (MTT) assay and plaque reduction assay (PRA). The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR (qPCR). Cytokine (IFN-γ, TNF-α) mRNA expressions after emodin treatment (7.5, 15, 30 μmol/L) were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration (EC50) ranging from 13.06 to 14.27 μmol/L and selectivity index (SI) being 5.38–6.41 μmol/L. However, emodin couldn’t directly inactivate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0–4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.

  • Shui-xia Zhang , Yi-hao Yao , Shun Zhang , Wen-jie Zhu , Xiang-yu Tang , Yuan-yuan Qin , Ling-yun Zhao , Cheng-xia Liu , Wen-zhen Zhu

    The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson’s correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and–0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL ≤0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL ≤0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.

  • Rong Liu , Xin-lin Chen , Xiao-hong Yang , Hui-jing Ma

    This study sought to evaluate the contribution of two-dimensional ultrasound (2D-US) and three-dimensional skeletal imaging ultrasound (3D-SUIS) in the prenatal diagnosis of sirenomelia. Between September 2010 and April 2014, a prospective study was conducted in a single referral center using 3D-SUIS performed after 2D-US in 10 cases of sirenomelia. Diagnostic accuracy and detailed findings were compared with postnatal three-dimensional helical computed tomography (3D-HCT), radiological findings and autopsy. Pregnancy was terminated in all 10 sirenomelia cases, including 9 singletons and 1 conjoined twin pregnancy, for a total of 5 males and 5 females. These cases of sirenomelia were determined by autopsy and/or chromosomal examination. Initial 2D-US showed that there were 10 cases of oligohydramnios, bilateral renal agenesis, bladder agenesis, single umbilical artery, fusion of the lower limbs and spinal abnormalities; 8 cases of dipus or monopus; 2 cases of apus; and 8 cases of cardiac abnormalities. Subsequent 3D-SUIS showed that there were 9 cases of scoliosis, 10 cases of sacrococcygeal vertebra dysplasia, 3 cases of hemivertebra, 1 case of vertebral fusion, 3 cases of spina bifida, and 5 cases of rib abnormalities. 3D-SUIS identified significantly more skeletal abnormalities than did 2D-US, and its accuracy was 79.5% (70/88) compared with 3D-HCT and radiography. 3D-SUIS seems to be a useful complementary method to 2D-US and may improve the accuracy of identifying prenatal skeletal abnormalities related to sirenomelia.

  • Tai-lang Yin , Yi Zhang , Sai-jiao Li , Meng Zhao , Jin-li Ding , Wang-ming Xu , Jing Yang

    Whether the type of culture media utilized in assisted reproductive technology has impacts on laboratory outcomes and birth weight of newborns in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was investigated. A total of 673 patients undergoing IVF/ICSI and giving birth to live singletons after fresh embryo transfer on day 3 from Jan. 1, 2010 to Dec. 31, 2012 were included. Three types of culture media were used during this period: Quinn’s Advantage (QA), Single Step Medium (SSM), and Continuous Single Culture medium (CSC). Fertilization rate (FR), normal fertilization rate (NFR), cleavage rate (CR), normal cleavage rate (NCR), good-quality embryo rate (GQER) and neonatal birth weight were compared using one-way ANOVA and χ2 tests. Multiple linear regression analysis was performed to determine the impact of culture media on laboratory outcomes and birth weight. In IVF cycles, GQER was significantly decreased in SSM medium group as compared with QA or CSC media groups (63.6% vs. 69.0% in QA; vs. 71.3% in CSC, P=0.011). In ICSI cycles, FR, NFR and CR were significantly lower in CSC medium group than in other two media groups. No significant difference was observed in neonatal birthweight among the three groups (P=0.759). Multiple linear regression analyses confirmed that the type of culture medium was correlated with FR, NFR, CR and GQER, but not with neonatal birth weight. The type of culture media had potential influences on laboratory outcomes but did not exhibit an impact on the birth weight of singletons in ART.

  • Hong-fang Yuan , Martin Kuete , Li Su , Fan Yang , Zhi-yong Hu , Bo-zhen Tian , Hui-ping Zhang , Kai Zhao

    Human sperm DNA is an important genetic and epigenetic material, whose chromatin structure differs from that of somatic cells. As such, conventional methods for DNA extraction of somatic cells may not be suitable for obtaining sperm DNA. In this study, we evaluated and compared three sperm DNA extraction techniques, namely, modified guanidinium thiocyanate method (method A), traditional phenol-chloroform method (method B), and TianGen kit method (method C). Spectrophotometry and agarose gel electrophoresis analyses showed that method A produced DNA with higher quantity and purity than those of methods B and C (P<0.01). PCR results revealed that method A was more reliable in amplifying DEAD-box polypeptide 4 (DDX4) and copy number variations (CNVs) than methods B and C, which generated false-positive errors. The results of sperm DNA methylation assay further indicated that methods A and B were effective, and the former yielded higher quantitative accuracy. In conclusion, the modified guanidinium thiocyanate method provided high quality and reliable results and could be an optimal technique for extracting sperm DNA for methylation assay.