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International Journal Of Clinical And Experimental Medicine[JOURNAL]

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The BRAF V600E mutation predicts poor survival outcome in patients with papillary thyroid carcinoma: a meta analysis.

Li J, Zhang S, Zheng S … +2 more , Zhang D, Qiu X

Int J Clin Exp Med · 2015 · PMID 26885200

INTRODUCTION: There have been contradictory data on whether or not BRAF V600E mutation should be regard as a poor prognosis predictor of papillary thyroid carcinoma (PTC). To settle down the conflict, this metaanalysis i... INTRODUCTION: There have been contradictory data on whether or not BRAF V600E mutation should be regard as a poor prognosis predictor of papillary thyroid carcinoma (PTC). To settle down the conflict, this metaanalysis is prepared to clarify the present prognostic role of BRAF V600E mutation in patients with PTC. METHODS AND MATERIALS: The relevant published researches were incorporated according to the defined inclusion/exclusion criteria from PubMed. The effect sizes of outcome parameters were estimated by hazard ratios (HRs). RESULTS: The current meta-analysis included 19 researches with a total of 6087 patients. We have found that patients with BRAF V600E mutation have a poor overall survival (the pooled HR=2.91, 95% confidence interval (CI): 1.35-6.29). Furthermore, subgroup analysis of the recurrence-free survival (RFS) of PTC patients by races indicated that BRAF V600E mutation predicts poor RFS of patients (the pooled HR=1.63, 95% CI: 1.37-1.93), both Caucasian (the pooled HR=1.57, 95% CI: 1.30-1.90) and Asian (the pooled HR=1.91, 95% CI: 1.28-2.87). CONCLUSIONS: The poor prognosis predicted role of BRAF V600E mutation in PTC was certified from the current meta-analysis. The BRAF V600E mutation may be used as a prognostic predictor of patients with PTC.

Comparison of pullout strength of the thoracic pedicle screw between intrapedicular and extrapedicular technique: a meta-analysis and literature review.

Wang H, Wang H, Sribastav SS … +7 more , Ye F, Liang C, Li Z, Wang J, Liu H, Wang X, Zheng Z

Int J Clin Exp Med · 2015 · PMID 26885199

BACKGROUND: Intrapedicular fixation in thoracic spine is often limited, because of high risk of complication, especially in scoliosis patients. Extrapedicular screws fixation techniques provide an alternate solution for... BACKGROUND: Intrapedicular fixation in thoracic spine is often limited, because of high risk of complication, especially in scoliosis patients. Extrapedicular screws fixation techniques provide an alternate solution for extremely small or abnormal thoracic pedicles deformity. However, the pullout resistance of extrapedicular screws has not been clearly defined. The aim of our study was to systematically review the existing evidence regarding the pullout resistance of thoracic extrapedicular screws compared with intrapedicular screws. METHODS: A systematic search of all studies published through Nov 2014 was performed using Medline, EMBASE, OVID and other databases. All studies that compared the pullout resistance of thoracic extrapedicular screws with intrapedicular screws were selected. The data from the included studies were extracted and analyzed regarding pullout resistance force. Forest plots were constructed to summarize the data and compare the biomechanical stability achieved. RESULTS: Five studies were included, with a total of 27 cadaveric specimens and 313 screws. The vertebral levels of the cadavers potted were T1-T8, T2-T12, T7-T9, T6-T11 and T4-T12 respectively. Overall, the results demonstrated that there was no significant difference in ultimate pullout strength between intrapedicular screws and extrapedicular screws (95% CI=-63.73 to 27.74; P=0.44); extrapedicular screws significantly increased the length of placements by a mean of 6.24 mm (95% CI=5.38 to 7.10; P<0.001); while the stiffness in intrapedicular screws was significantly stronger by a mean of 45.82 N/mm compared with extrapedicular screws (95% CI=-70.09 to -21.56; P<0.001). CONCLUSIONS: Meta-analysis of the existing literature showed that thoracic extrapedicular screws provided comparable but slightly lower pullout strength compared with intrapedicular screws, extrapedicular screws placement is much safer than intrapedicular screws. So thoracic extrapedicular screws offer a good alternative when it is hard to insert by intrapedicular approach, especially in scoliosis patients with severe vertebral deformities.

Evaluation of miR-29c, miR-124, miR-135a and miR-148a in predicting lymph node metastasis and tumor stage of gastric cancer.

Liu L, Ye JX, Qin YZ … +2 more , Chen QH, Ge LY

Int J Clin Exp Med · 2015 · PMID 26885198

MicroRNAs (miRNAs) are small noncoding RNA that have diverse functions in different biological process. The aim of this study was to evaluate the predictive ability of miR-29c, miR-124, miR-135a and miR-148a for lymph no... MicroRNAs (miRNAs) are small noncoding RNA that have diverse functions in different biological process. The aim of this study was to evaluate the predictive ability of miR-29c, miR-124, miR-135a and miR-148a for lymph node metastasis (LNM) and tumor stage in gastric cancer. The expression of these miRNAs was detected and quantitated in gastric cancer tissues and in adjacent normal tissues from 60 patients by quantitative real-time reverse transcription-polymerase chain reaction. CT imaging and clinicopathologic characteristics of these patients were performed. The result of this study was that these miRNAs were down-regulated in gastric cancer tissues; The low expression of miR-124 and miR-135a in LNM group and tumor III-IV stages (P < 0.01) presented the potential correlation with LNM and tumor stage; The two miRNAs were highly correlated with r = 0.730. Receiver operating characteristic curve analysis showed that miR-124 had better predictive ability to identify LNM and tumor stage. It could discriminate non-LNM from LNM with 80.0% sensitivity and 80.0% specificity and discriminate tumor Ι-II stages from tumor III-IV stages with 71.9% sensitivity and 75.0% specificity at the best cut-off value of 0.0125. Compared with CT imaging, miR-124 had similar specificity (0.800 versus 0.900, P = 0.508) but higher sensitivity (0.800 versus 0.500, P = 0.022) for lymph node assessment; Combined of miR-124 and CT imaging, The sensitivity and specificity of assessing LNM were raised to 83.3% and 90.0% respectively. Taken together, miR-124 may be a predictor for LNM and tumor stage in gastric cancer.

Erythromycin enhances the anti-inflammatory activity of budesonide in COPD rat model.

Miao L, Gao Z, Huang F … +7 more , Huang S, Zhang R, Ma D, Wu Q, Li F, Chen H, Wang J

Int J Clin Exp Med · 2015 · PMID 26885197

Glucocorticoids (GCs) have been widely applied to treat patients with chronic obstructive pulmonary disease (COPD). But the effect of GCs was not ideal. This study was to observe whether erythromycin could enhance the an... Glucocorticoids (GCs) have been widely applied to treat patients with chronic obstructive pulmonary disease (COPD). But the effect of GCs was not ideal. This study was to observe whether erythromycin could enhance the anti-inflammatory activity of budesonide in COPD model rats and to explore the mechanism involved. In this study, male Sprague-Dawley rats were divided into five groups: healthy control group (H group), COPD model group (C group), erythromycin group (E group), budesonide group (B group) and erythromycin + budesonide group (E+B group). The rats in groups of C, E, B and E+B were developed into COPD models. Different groups were given different drug interventions. The levels of 8-iso-PGF2α, IL-8, and TNF-α in BALF and serum were measured with ELISA. The protein expression levels of HDAC2, PI3K, and p-AKT in lung tissue were measured with Western-blot and immunohistochemistry. The levels of 8-iso-PGF2α, IL-8, and TNF-α in BALF and serum were lower in E+B group than those in B group and C group (all P<0.001).The protein expression level of HDAC2 was higher and PI3K and p-AKT were lower in E+B group than those in B group and C group (all P<0.001). Moreover, the expression levels of HDAC2 were negatively correlated with the levels of 8-iso-PGF2α, IL-8 and TNF-α both in serum and BALF and the expression levels of PI3K and p-AKT among the five groups, with all P<0.001. We conclude that erythromycin can enhance the anti-inflammatory activity of budesonide in COPD model rats, possibly through inhibiting the PI3K/AKT pathway and enhancing the activity of HDAC2.

Cytoplasmic EpCAM over-expression is associated with favorable clinical outcomes in pancreatic cancer patients with Hepatitis B virus negative infection.

Meng Y, Xu BQ, Fu ZG … +4 more , Wu B, Xu B, Chen ZN, Li L

Int J Clin Exp Med · 2015 · PMID 26885196

The identification of reliable prognostic markers that distinguish patients' status and predict therapeutic response can improve the clinical outcomes of pancreatic cancer patients. The epithelial cell adhesion molecule... The identification of reliable prognostic markers that distinguish patients' status and predict therapeutic response can improve the clinical outcomes of pancreatic cancer patients. The epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in cancers and serves as a prognosis factor. Generally, membranous EpCAM expression in cancer cells and its clinical significance are evaluated. However, there is also an evidence of cytoplasmic EpCAM distribution in cancer cells. Hence, we investigated which kind of the immunostaining pattern in pancreatic cancer patients was, and whether membranous or cytoplasmic immunostaining had clinical significance. We determined the cytoplasmic or membranous EpCAM expression by a well-established immunohistochemical staining protocol in 157 pairs of carcinoma and paired adjacent non-tumor pancreatic tissue samples using the EpCAM-specific antibody. Furthermore, we evaluated the relationship between tumoral EpCAM expression of resected specimens and patient's overall survival as well as other biological variables like clinical prognosis by Kaplan-Meier method and χ(2) test. We found that pancreatic cancer patients had expressed higher level of cytoplasmic EpCAM but lower level of membranous EpCAM, and their expressions were significantly correlated. Cytoplasmic EpCAM acted as a favorable prognosis factor on survival time in patients with HBV negative infection. Pancreatic cancer patients with cytoplasmic EpCAM over-expression and negative Hepatitis B virus infection might benefit further from post-surgery chemotherapy. These data suggested a potential role of cytoplasmic EpCAM in predicting patient's prognosis and determining therapeutic strategy.

Clinicopathological significance of NGX6 expression in breast cancer and its relationship to angiogenesis.

Xiao J, Mao Y, Zhou Y … +1 more , Xiang K

Int J Clin Exp Med · 2015 · PMID 26885195

OBJECTIVE: The aim was to explore clinicopathological significance of Nasopharyngeal carcinoma-associated gene 6 (NGX6) expression in breast cancer and its relationship to angiogenesis. METHODS: Clinicopathological featu... OBJECTIVE: The aim was to explore clinicopathological significance of Nasopharyngeal carcinoma-associated gene 6 (NGX6) expression in breast cancer and its relationship to angiogenesis. METHODS: Clinicopathological feature of 168 patients with breast cancer were analyzed. NGX6 expression and microvessel density (MVD) in tumor tissue were measured using immunohistochemistry methods. The association of NGX6 expression with MVD and clinicopathological features was assessed. RESULTS: Among 168 cases of breast cancer, NGX6 positive expression were found in 92 (54.8%) cases and NGX6 negative expression were found in 76 (45.2%) cases. Incidence rate of large size tumor, high tumor node metastasis (TNM) stage and lymph node metastasis in NGX6 negative expression group were higher than NGX6 positive expression group in breast cancer (P=0.003, 0.007, and 0.003, respectively). MVD in NGX6 negative expression group is 22.5±4.8, MVD in NGX6 positive expression group is 15.2±4.2. MVD in the NGX6 negative expression group was significantly higher than the NGX6 positive expression group (P<0.05). CONCLUSION: The expression of NGX6 was closely associated with tumor size, TNM stage, lymph node metastasis and MVD. NGX6 is involved in metastasis and angiogenesis activity of breast cancer. The study may provide a theoretical basis for anti-angiogenic therapy of breast cancer.

Eupatilin protects against tumor necrosis factor-α-mediated inflammation inhuman umbilical vein endothelial cells.

Yu K, Li XM, Xu XL … +2 more , Zhang RY, Cong HL

Int J Clin Exp Med · 2015 · PMID 26885194

Inflammatory responses in the blood vessel play a pivotal role in the pathogenesis of atherosclerosis. Eupatilin, a flavone derived from Artemisia princepsPampanini, has various pharmacological activities, including anti... Inflammatory responses in the blood vessel play a pivotal role in the pathogenesis of atherosclerosis. Eupatilin, a flavone derived from Artemisia princepsPampanini, has various pharmacological activities, including antioxidant, anti-tumor, and anti-inflammatory capacities. However, there has been no research examining the function of eupatilin on vascular inflammation. Therefore, the aim of this study was to investigate the effects of eupatilin on tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVECs) activation and the underlying molecular mechanisms. Our findings showed that eupatilin reduced U937 cells adhesion to TNF-α-stimulated HUVECs and attenuated TNF-α-induced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs, as well as the production of intracellular reactive oxygen species (ROS). Moreover, eupatilininhibits TNF-α-induced phosphorylation of NF-kB p65 and MAPKs in HUVECs. Taken together, the results of the present study suggest that eupatilin inhibited inflammatory reaction through suppressing the ROS/MAPK-NF-ĸB pathway in HUVECs. Thus, eupatilin is proposed as an effective new anti-inflammatory agent to suppress vascular inflammation, and further prevent atherosclerosis.

RKIP suppresses the proliferation and invasion ofchoriocarcinoma cells through inhibiting the MAPK signaling pathway.

Zhang M, Zhang D, Fan Q

Int J Clin Exp Med · 2015 · PMID 26885193

Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), has been identified as a metastasis suppressor gene. However,... Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), has been identified as a metastasis suppressor gene. However, the role of RKIP in human choriocarcinoma remains undetermined. Therefore, in the present study, we investigated the expression of RKIP in human choriocarcinoma cells and evaluated the effects of RKIP on choriocarcinoma cell proliferation and invasion. Our results indicated that RKIP was lowly expressed in human choriocarcinoma cells. Overexpression of RKIP inhibits choriocarcinoma cell proliferation, migration and invasion, promotes the apoptosis of choriocarcinoma cells. Furthermore, overexpression of RKIP significantly inhibited the expression of MEK and ERK phosphorylation in choriocarcinoma cells. Taken together, these data suggest that RKIP suppresses cell proliferation and invasion in choriocarcinoma cells through inhibiting the MAPK signaling pathway, implying that RKIP may serve as a potential molecular target for the treatment of human choriocarcinoma.

Therapeutic effects of OP-1 on metal wear particle induced osteoblasts injury in vitro.

Sun G, Chen J, Yang S … +4 more , Parker TM, Goodman GM, Hasama JM, Zhao J

Int J Clin Exp Med · 2015 · PMID 26885192

Aseptic lossening is a main reason for the revision of total joint arthroplasty. Metal-wear particles induced deregulation of bone resorption or formation has been considered as the major process of aseptic lossening. Os... Aseptic lossening is a main reason for the revision of total joint arthroplasty. Metal-wear particles induced deregulation of bone resorption or formation has been considered as the major process of aseptic lossening. Osteogenic protein-1 (OP-1) can be used to improve bone formation. However, such effect is not clearly understood after the metal-wear particles injury. Here, we investigated the molecular mechanisms by which OP-1 regulates the activity of bone formation and anti-inflammatory after injury. Results showed that OP-1 increased cell viability and bone formation ability of impaired osteoblast cells at 72 hours after being injured by cobalt particles. Pathway analyses revealed that both mRNA and protein levels of Smad1 and Smad5 were significantly increased upon the treatment of OP-1 in the cell injury model. Similarly, runt-related transcription factor 2 (Runx2) was also significantly upregulated in the OP-1 treated cells. Moreover, treatment with OP-1 inhibited the secretion of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-18 in cobalt impaired cells. Collectively, these results suggest that OP-1 could inhibit cobalt particles induced cell injury by activating Smad1, Smad5, and Runx2, and such procedure is accompanied by anti-inflammatory reaction.

Association of risk of non-Hodgkin's lymphoma with hepatitis B virus infection: a meta-analysis.

Qi Z, Wang H, Gao G

Int J Clin Exp Med · 2015 · PMID 26885191

OBJECTIVE: A meta-analysis was carried out to systematically evaluate the correlation between hepatitis B virus (hepatitis B virus, HBV) infection and risk of non-Hodgkin's lymphoma (non-Hodgkin lymphoma, NHL). METHODS:... OBJECTIVE: A meta-analysis was carried out to systematically evaluate the correlation between hepatitis B virus (hepatitis B virus, HBV) infection and risk of non-Hodgkin's lymphoma (non-Hodgkin lymphoma, NHL). METHODS: We searched Medline, EMBASE, PubMed, Cochrane Library, Chinese Biomedical Literature Database, Chinese Journal Full-text Database, Chinese scientific journals full text databases and collected information about HBV infection and risk of NHL associated case-control studies. Two reviewers extracted useful information which were included in the study independently, and Revman 5.2 was used for meta-analysis. RESULTS: A total of 24 studies were included in this research. Meta-analysis showed that among all of the included studies the heterogeneity were existed (I(2) = 76%, P<0.05). With random effects model the OR was 2.39 (95% CI, 1.93-3.96), indicating infection rate in NHL patients with HBV was higher than that in the control group. Subgroup analysis according to ethnicity suggested that HBV infection were associated with NHL risk both in Asian (OR = 2.46, 95% CI: 2.01, 3.00, P<0.001) and Caucasian (OR = 2.15, 95% CI: 1.37, 3.37, P<0.001) population. CONCLUSION: HBV infection may increase the risk of NHL, but it still need a large number of experiments and epidemiological studies to verify.

Effects of Ukrain on intestinal apoptosis caused by ischemia-reperfusion injury in rats.

Akcılar R, Akcılar A, Koçak C … +5 more , Koçak FE, Bayat Z, Şimşek H, Şahin S, Savran B

Int J Clin Exp Med · 2015 · PMID 26885190

BACKGROUND: To investigate the antiapoptotic effect of Ukrain on intestinal lesion induced by mesenteric ischemia-reperfusion (I/R) injury. METHODS: Male Sprague-Dawley rats were divided into three groups: laparotomy (L)... BACKGROUND: To investigate the antiapoptotic effect of Ukrain on intestinal lesion induced by mesenteric ischemia-reperfusion (I/R) injury. METHODS: Male Sprague-Dawley rats were divided into three groups: laparotomy (L), I/R, and Ukrain and I/R (U + I/R). In the U + I/R group, Ukrain (7 mg/kg) was given by intraperitoneal at the beginning of the study. 1 h after ukrain application, ischemia was induced for 30 minutes, and reperfusion was subsequently allowed for 120 minutes in the I/R and U + I/R groups. Rats were sacrificed at the end of reperfusion and intestinal tissues were collected for biochemical and molecular examination. Intestinal tissues caspase 3 protein were assayed. Serum Bcl-xL and iNOS were measured. The expression level of caspase-3, Bcl-xL and iNOS in intestinal tissue of rats were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Levels of serum iNOS and mRNA expression were increased in the I/R and decreased in the U + I/R group. In addition, levels of the proapoptotic gene caspase-3 protein and mRNA expression were increased in the I/R and decreased in the U + I/R group. Levels of the antiapoptotic gene Bcl-xL serum and mRNA expression were increased in the U + I/R group. CONCLUSIONS: Ukrain can reduce the ischemia-reperfusion injury in the intestinal tissue by inhibiting the cell apoptosis. The mechanism may be correlated with increased Bcl-xL mRNA expressions and decreased mRNA expressions of Caspase-3 and iNOS.

Roles of miR-186 and PTTG1 in colorectal neuroendocrine tumors.

Wang M, Xia X, Chu W … +4 more , Xia L, Meng T, Liu L, Liu Y

Int J Clin Exp Med · 2015 · PMID 26885189

OBJECTIVES: This work aims to investigate the expression of miRNA-186 in patients with colorectal cancer tissues, blood and feces and its roles in regulating the infiltration and invasion in colorectal cancer. METHODS: T... OBJECTIVES: This work aims to investigate the expression of miRNA-186 in patients with colorectal cancer tissues, blood and feces and its roles in regulating the infiltration and invasion in colorectal cancer. METHODS: Totally 39 patients with surgical resection were included from August 2012 to February 2015 in Jilin Province People's Hospital as the Colorectal Neuroendocrine tumor (CNET). Peripheral blood, stool, and resected tumor tissues with adjacent normal of each patient was collected. In the same period, the blood and stool from 25 patients with hemorrhoids or other non-neoplastic diseases were collected and these samples used as clinical control group. MiR-186 expression and PTTG1 (pituitary tumor-transforming 1) expression were detected by quantitative Real-Time PCR (qRT-PCR). The PTTG1 protein expression in tumor samples were detected by Western Blot, while its expression in blood and stool were detected by Elisa. RESULTS: Compared with the control group, the expression of PTTG1 mRNA and protein was significantly up-regulated in tumor samples, blood, and stool of patients with CNET, while the expression of miR-186 was down-regulated (P < 0.05). CONCLUSION: PTTG1 expression was significantly up-regulated in patients with CNET, which was induced by the down-regulated miR-186. MiR-186 may participate in the regulation of infiltration and invasion in CNET patients through targeting PTTG1 expression.

Targeting SLUG sensitizes leukemia cells to ADR-induced apoptosis.

Wei CR, Liu J, Yu XJ

Int J Clin Exp Med · 2015 · PMID 26885188

BACKGROUND AND AIMS: Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In... BACKGROUND AND AIMS: Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug's ability to silence expression suppresses the growth of leukemia HL-60 cells and/or sensitizes leukemia HL-60 cells to adriamycin (ADR) through induction of apoptosis. METHODS: SLUG siRNA was transfected into the HL-60 and HL-60(ADR) cell lines (an adriamycin resistant cell line). The stably SLUG siRNA transfected HL-60 and HL-60(ADR) cells was transiently transfected with PUMA siRNA. The mRNA and protein expression of SLUG and PUMA were determined by Quantitative real-time RT-PCR and Western blot assay. The effects of SLUG siRNA alone or combined with ADR or PUMA siRNA on growth and apoptosis in HL-60 and HL-60(ADR) cells was detected by MTT, ELISA and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. RESULTS: The results showed that SLUG was less expressed in the HL-60 cells, and high expressed in the HL-60(ADR) cells. Obvious down-regulation of SLUG mRNA and protein levels and up-regulation of PUMA mRNA and protein levels after SLUG siRNA transfection was showed in the HL-60(ADR) cells. Treatment with ADR induced SLUG mRNA and protein in the HL-60 cells. Significant positive correlation was observed between basal SLUG mRNA and protein and ADR sensitivity. SLUG gene silencing by SLUG siRNA transfection inhibited growth and induced apoptosis, and increased ADR killing of the HL-60 and HL-60(ADR) cell lines. After the SLUG siRNA transfected HL-60 and HL-60(ADR) cells was transiently transfected with PUMA siRNA, did not increase ADR killing of the HL-60 and HL-60(ADR) cell lines. CONCLUSION: SLUG level positively correlated with sensitivity to ADR. SLUG siRNA could effectively reduce SLUG expression and induce PUMA expression and restore the drug sensitivity of resistant leukemic cells to conventional chemotherapeutic agents.

Baicaleininhibits VSMCs proliferation via regulating LncRNAAK021954 gene expression.

Zhang Y, Ma G, Li C … +3 more , Cao Z, Qie F, Xu X

Int J Clin Exp Med · 2015 · PMID 26885187

Atherosclerosis is responsible for the global medical burden of cardiovascular diseases, of which the proliferation of vascular smooth muscle cells (VSMCs) plays a key role in the development. Recent evidences demonstrat... Atherosclerosis is responsible for the global medical burden of cardiovascular diseases, of which the proliferation of vascular smooth muscle cells (VSMCs) plays a key role in the development. Recent evidences demonstrated that baicalein could attenuate the proliferation of VSMCs and had no influence on VSMCs migration. However, the precise molecular mechanisms of baicalein inhibiting the proliferation of VSMCs were not clear. In this study, we investigated the viability and apoptosis behaviour of VSMCs and its downstream molecular changes with exposed to different dose of baicalein. Firstly, we observed significant reducing in the VSMCs proliferation and decreasing of FGF18 expression in a dose dependent manner after addition of baicalein for 24 h and 72 h. Moreover, the mRNA expression profile of VSMCs after treatments was evaluated by microarray analysis. Microarray analysis showed that long non-coding RNA (lncRNA) AK021954 gene expression was significantly increased in the baicalein treated group compared with the control group. Inversely, the VSMCs proliferation showed a notable increase after small silent RNA of lncRNAAK021954 treatment. These results indicated that lncRNAAK021954 gene and FGF18 involved in baicalein inhibiting the proliferation of VSMCs. It may provide a promising method in treatment of atherosclerosis.

Arginine vasopressin antagonist tolvaptan in the treatment of heart failure: a meta-analysis of randomized controlled trials.

Yang CJ, Yang J, Yang J … +1 more , Fan ZX

Int J Clin Exp Med · 2015 · PMID 26885186

BACKGROUND: Tolvaptan can promote water clearance without a deterioration of serum electrolytes in HF patients, but its efficacy and safety were unclear. We performed a meta-analysis of randomized controlled trials (RCTs... BACKGROUND: Tolvaptan can promote water clearance without a deterioration of serum electrolytes in HF patients, but its efficacy and safety were unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the efficacy and safety of tolvaptan in the treatment of patients hospitalized for heart failure (HF). METHODS: In Oct 2014, a literature search was started and found all studies conducted from 2000 to 2014. We systematically searched the literature through the MEDLINE database and EMBASE database. Quality assessments were evaluated with Jadad quality scale. Data were extracted considering the characteristics of efficacy and safety designs. RESULT: Eight RCTs enrolling 13453 participants satisfying the inclusion criteria were finally analyzed. There were significant decreases of body weight (MD=-0.87, 95% CI=-0.94 to -0.80, P<0.001) among all subgroups. Significant increase of serum sodium was found between tolvaptan and placebo groups at day 1 (MD=2.93, 95% CI=2.70 to 3.16, P<0.001) and at day 7 or discharge (MD=3.10, 95% CI=2.78 to 3.42, P<0.001). There were significant differences between the day 1 subgroup and day 7 or discharge subgroup (MD=2.99, 95% CI=2.80 to 3.18, P<0.001). A statistical significant improve in dyspnea (RR=1.10, 95% CI=1.07 to 1.13, P<0.001) and edema (RR=1.05, 95% CI=1.02 to 1.08, P<0.001) occurred, whereas there was no difference in rales (RR=2.38, 95% CI=0.89 to 6.38, P=0.08) and pulmonary congestion (RR=1.02, 95% CI=0.71 to 1.45, P=0.93). Pooled effect measure in the outcome of common adverse event (RR=1.08, 95% CI=0.99 to 1.18, P=0.08) and serious adverse (RR=0.96, 95% CI=0.88 to 1.04, P=0.29) event both show no significant occurrence. CONCLUSION: Tolvaptan decreases body weight, increases serum sodium, and improves congestion without significant increasing adverse events in HF patients.

Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects.

Zong Q, Ni D, Li L … +1 more , Shi Y

Int J Clin Exp Med · 2015 · PMID 26885185

This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the associa... This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age < 40, sample size > 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease.

Anti-arrhythmic effects of atrial ganglionated plexi stimulation is accompanied by preservation of connexin43 protein in ischemia-reperfusion canine model.

Wang S, Li H, Yu L … +6 more , Chen M, Wang Z, Huang B, Zhou L, Zhou X, Jiang H

Int J Clin Exp Med · 2015 · PMID 26885184

BACKGROUND: Vagal nerve stimulation (VNS) has been shown to provide a protective effect against ischemia/reperfusion (I/R)-related arrhythmias by preventing the loss of Connexin43 (Cx43). Our previous studies showed that... BACKGROUND: Vagal nerve stimulation (VNS) has been shown to provide a protective effect against ischemia/reperfusion (I/R)-related arrhythmias by preventing the loss of Connexin43 (Cx43). Our previous studies showed that atrial epicardial ganglionated plexus stimulation (GPS) might exert a VNS-like effect on ventricular electrophysiology. OBJECTIVES: To investigate whether GPS could preserve Cx43 and reduce I/R induced ventricular arrhythmia. METHODS: Sixteen dogs were randomly divided into GPS group (N = 8, receiving GPS) and Sham group (N = 8, receiving sham GPS). Ventricular effective refractory period (ERP) and heart rate variability (HRV) were measured at baseline and 1 h after GPS. Myocardial I/R was then performed. Ventricular arrhythmia occurred during the first hour after reperfusion was measured and myocardial tissue from the peri-infarct zone was excised for immunohistological analysis. In another 4 dogs (Control group, receiving sham GPS and sham I/R), myocardial tissue from the corresponding area was also excised. RESULTS: Compared with the Sham group, GPS caused a significant increase in ventricular ERP and HRV, and a significant decrease in I/R-induced ventricular arrhythmias. Western blotting revealed a marked reduction in the amount of phosphorylated Cx43 and total Cx43 in the Sham group, whereas no significant change was observed in the GPS group compared with the Control group. Immunohistochemistry results confirmed that the myocardial I/R-induced loss of phosphorylated Cx43 from the intercellular junctions was prevented by GPS. CONCLUSION: GPS protects against I/R induced ventricular arrhythmias, accompanied by preserving Cx43.

The Chronic Kidney Disease Epidemiology Collaboration equation improves the detection of hyperfiltration in Chinese diabetic patients.

Zhao F, Zhang L, Lu J … +7 more , Guo K, Wu M, Yu H, Zhang M, Bao Y, Chen H, Jia W

Int J Clin Exp Med · 2015 · PMID 26885183

OBJECTIVE: Hyperfiltration confers an increased risk of diabetic nephropathy. Early detection can ensure timely intervention and improved treatment outcomes. Because GFR is known to be affected by hyperglycemia, the aim... OBJECTIVE: Hyperfiltration confers an increased risk of diabetic nephropathy. Early detection can ensure timely intervention and improved treatment outcomes. Because GFR is known to be affected by hyperglycemia, the aim of this study was to compare the influence of hyperglycemia on GFR estimations calculated by the CKD-EPI equation, the CG equation, and the MDRD equations in estimating hyperfiltration in Chinese diabetic patients. MATERIALS AND METHODS: The performance of the equations, compared with the measured (99)mTc-DTPA glomerular filtration rate was analyzed in 3492 diabetic patients. Bias, precision, and accuracies were compared with respect to HbA1c status. The Bland-Altman method was used to evaluate the agreement among the equations with respect to the mGFR, and the receiver-operating characteristic curve method was used to evaluate diagnostic value of the three equations with respect to the detection of moderate renal failure and hyperfiltration. RESULTS: The mean absolute bias was the smallest for the CKD-EPI equation in the HbA1c < 7.2% cohort, and the highest accuracy within ± 15% and ± 30% was also reached with the CKD-EPI equation in both cohorts. For the detection of hyperfiltration, the CKD-EPI equation exhibited the best performance with the greatest combination of sensitivity and specificity. The biases of the three equations were significantly higher in the HbA1c ≥ 10.5% subgroup compared with the HbA1c < 7.2% cohort. CONCLUSION: The CKD-EPI equation can be used as a screening tool for hyperfiltration and appears to be a more generalizable and accurate equation for estimating GFR in Chinese diabetic patients.

Clinical and prognostic significance of HIF-1α in glioma patients: a meta-analysis.

Liu Q, Cao P

Int J Clin Exp Med · 2015 · PMID 26885182

Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1α) was shown to be involved in the pathophysiology and management of glioma, and... Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1α) was shown to be involved in the pathophysiology and management of glioma, and might offer a therapeutic target. However, the results remain inconclusive. The purpose of this study was to systematically investigate the clinical and prognostic significance of HIF-1α expression in patients with glioma. Relevant studies published between 2000 and 2015 were searched in the electronic databases. The odds ratio (OR), risk ratio (RR) and mean difference (MD) with their 95% confidence intervals (CI) were employed to calculate the strength of significance. Finally, a total of 24 articles were retrieved, including 1422 glioma patients. No significant heterogeneity was presented between studies (I(2)<50%, P>0.01). Overall, our results showed that HIF-1α expression was significantly associated with high WHO grade (III+IV) of glioma (OR=8.59, 95% CI=6.56-11.24, P<0.00001). This significant relationship was also found between HIF-1α expression and microvascular density (MD=26.32, 95% CI=14.48-38.16, P<0.0001), overall survival (OS) (3-year OS: RR=0.48, 95% CI=0.35-0.66, P<0.00001; 2-year OS: RR=0.53, 95% CI=0.38-0.73, P<0.0001; 1-year OS: RR=0.79, 95% CI=0.66-0.95, P=0.01), and the cumulative survival time. However, HIF-1α expression was not associated with age and gender of glioma patients (P>0.05). In conclusions, our results suggested that HIF-1α expression was associated with high grade of glioma and OS, indicating that HIF-1α could predict prognosis and provide clinical insights into the therapeutic strategy for patients with glioma. More studies concerning other populations are also needed in the future research.

Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat.

Sun SJ, Wu XP, Song HL … +1 more , Li GQ

Int J Clin Exp Med · 2015 · PMID 26885181

Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, anti-inflammation... Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, anti-inflammation, etc. The aim of this study was to investigate the potential cardioprotective effects of baicalin ameliorates isoproterenol-induced acute myocardial infarction (AMI) through inducible nitric oxide synthase (iNOS), inflammation, oxidative stress and P38MAPK passageway in rat. Rat model of AMI was induced by isoproterenol (100 mg/kg) and then treated baicalin (various does of baicalin: 1 mg/kg, 10 mg/kg and 100 mg/kg, respectively) for 24 h. Infarct size, the heart weight to body weight ratio and creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) of rats with AMI induced by isoproterenol were used to evaluate curative effect of baicalin on AMI. Meanwhile, iNOS and phosphorylation-p38 MAPK (p-p38) protein expressions, inflammatory factor and oxidative stress were inspected using western blot and commercial kits, respectively. In the present study, pre-treatment with baicalin (10 or 100 mg/kg) significantly ameliorated infarct size, the heart weight to body weight ratio and CK, CK-MB, LDH and cTnT levels in rats with AMI induced by isoproterenol. iNOS protein expression, the serum TNF-α, IL-6, MDA and SOD levels and p-38 protein expressions were significantly suppressed by treatment with baicalin (10 or 100 mg/kg). These results suggest that acute treatment with baicalin ameliorates AMI, iNOS, inflammation, oxidative stress and P38MAPK pathway in rat with AMI induced by isoproterenol.
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