螺内酯对肝硬变门脉血流动力学的实验和临床研究

目的探索螺内酯对门脉高压实验犬和肝硬变患者门脉血流动力学的作用．方法用直接门脉插管测压和９９ｍＴｃＭＩＢＩ心肝放射性摄取比值（Ｈ／Ｌ）测定慢性胆总管结扎肝硬变犬（ｎ＝１６）门静脉压力和门体分流，口服螺内酯２０ｍｇ／（ｋｇ·ｄ）．肝硬变患者１４例测定Ｈ／Ｌ，门静脉内径和流速后口服螺内酯８０ｍｇ／ｄ，４ｗｋ为１疗程．结果完成试验的犬１３只治疗前后门脉压力（ｋＰａ）从２５９±０５１下降为２４２±０４７（Ｐ＜００５），Ｈ／Ｌ从０３３±００６降至０３０±００８（Ｐ＜００５）．１４例肝硬变患者治疗前后Ｈ／Ｌ值从１２０±０２６降为１０２±０３４（Ｐ＜００５），门脉内径（ｍｍ）从１３９±２３缩小为１２３±２０（Ｐ＜００５）．门静脉流速明显增加．结论螺内酯口服可降低门脉压力和门体分流．     

A meta-analysis of the associations between the Q141K and Q126X ABCG2 gene variants and gout risk

Background: Gout is an inflammatory disease in which genetic factors play a role. ABCG2 is a urate transporter, and the Q141K and Q126X variants of ABCG2 have been associated with a risk of developing gout, though previous studies of these associations have been inconsistent. Therefore, we conducted a meta-analysis to explore the relationship between these genetic variants and gout. Methods: We examined 8 electronic literature databases. In total, 9 eligible articles on the associations between the Q141K (rs2231142) and Q126X (rs72552713) variants and gout risk, including 11 case-control studies were selected. We used odds ratios (OR) and 95% confidence intervals (CI) to assess the strength of these relationships in dominant, recessive, and co-dominant models. Results: This study included 6652 participants (2499 gout patients and 4153 controls). The Q141K variant was found to significantly increase the risk of gout in Asians (dominant model: OR=2.64, 95% CI=2.04-3.43, P=0.02 for heterogeneity; recessive model: OR=3.19, 95% CI=2.56-3.97, P=0.28 for heterogeneity; co-dominant model: OR=1.37, 95% CI=1.18-1.59, P=0.09 for heterogeneity) and other populations (dominant model: OR=1.85, 95% CI=1.20-2.85, P<0.0001 for heterogeneity; recessive model: OR=3.78, 95% CI=2.28-6.27, P=0.19 for heterogeneity; co-dominant model: OR=1.48, 95% CI=1.26-1.74, P=0.19 for heterogeneity). The Q126X variant also significantly increased the risk of gout in Asians (dominant model: OR=3.87, 95% CI=2.07-7.24, P=0.06 for heterogeneity). Conclusions: These results suggest associations between the rs2231142 and rs72552713 ABCG2 gene polymorphisms and gout risk, which led to unfavorable outcomes. However, studies with larger sample sizes and homogeneous populations should be performed to confirm these results.     

Knockdown of WISP1 inhibit proliferation and induce apoptosis in ALL Jurkat cells

WISP1, a Wnt-induced secreted protein, has been found to have anticancer activity. ALL is a leading cause of death. Here we investigate the WISP1 effects on ALL Jurkat cells. Cell viability was assessed by CCK-8. Cell cycle and apoptosis were detected by flow cytometry. Mitochondrial membrane potential (MMP) was monitored using TMRM. Generation of reactive oxygen species (ROS) was quantified using DCFH-DA. Western blot was used to detect the expression of cell proliferation and apoptosis related genes. The results showed that knockdown of WISP1 significantly inhibited proliferation of Jurkat cells. Parallelly, cell cycle distribution was increased at G1 phase and apoptotic rate was induced after WISP1 knockdown. Furthermore, knockdown of WISP1 induced apoptosis of Jurkat cells was also associated with loss of MMP and generation of ROS. Western blot results showed that the protein expression p-AKT, PCNA, CDK1, P-ERK, CDK2, VEGF, VEGFR2 and Bcl2 were decreased, while the expression of Bax was up-regulated. In conclusion, WISP1 plays an important role in proliferation and apoptosis of Jurkat cells in mitochondria dependent pathway, the specific mechanisms need further study.     

Gliosarcoma with primitive neuroectodermal,osseous, cartilage and adipocyte differentiation: a case report

We describe a rare case of gliosarcoma with primitive neuroectodermal, osseous, cartilage and adipocyte differentiation. A 57-year-old man experienced a month history of headache, nausea and vomiting. Worse yet, the headache has become more severe for the past 6 days. Magnetic resonance (MR) images disclosed a lesion with operative indications located in the right frontal lobe. Then the tumor was macroscopically totally removed. Histologically, the tumor showed two kinds of components. One kind of the tumor cells appeared typical astrocytic tumor cells with anaplastic appearance. The other kind of the tumor cells appeared sheets of small round hyperchromatic cells, which presented a kind of pancreatic neuroendocrine tumor (PNET)-like structure. These sheets of small round cells were surrounded by a large number of relative-sparse-spindle cells. Multiple separate distinct areas of adipose tissue, osteoid matrix laid down and cartilage tissue were also identified. Immunohistochemically, a portion of typical astrocytic tumor cells and some small round hyperchromatic cells showed GFAP positivity. Small round hyperchromatic cells were positive for S-100, Fli-1, Nestin, MAP-2 and Syn. A large amount of relative sparse spindle cells (sarcomatous areas) were positive for vimentin. In addition, reticulin staining demonstrated expression of reticular fibers in relative-sparse-spindle cells areas but not in the astrocytic tumor cells and small round hyperchromatic cells areas. Molecular cytogenetic analyses demonstrated PTEN allele loss and no evidence of amplification of EGFR in both the astrocytic tumor cells, PNET-like structure and sparse spindle cells areas. These data suggest that this tumor was a gliosarcoma with primitive neuroectodermal, osseous, cartilage and adipocyte differentiation. To our knowledge, this is a rare gliosarcoma , reporting our additional new case would add to the better understanding of this tumor.     

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival

Introduction: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. Methods: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. Results: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). Conclusions: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.     

Anti-inflammatory and antioxidant effects of curcumin on acute lung injury in a rodent model of intestinal ischemia reperfusion by inhibiting the pathway of NF-Kb

Objective: To investigate the anti-inflammatory and antioxidant effect of curcumin on lung lesion induced by intestinal ischemia reperfusion injury (IIR). Methods: Rats were divided into four groups: sham, intestinal IIR (IIR), 1 mg/kg of curcumin treatment group (1 mg/kg), and 5 mg/kg of curcumin treatment group (5 mg/kg). Curcumin was given respectively (1 mg/kg and 5 mg/kg) following the above doses. IIR was produced by 1 h of intestinal ischemia followed by 2 h of reperfusion. Rats were sacrificed at the end of reperfusion and lung tissues were collected for biochemical and histopathological examination in 4 groups. Lung tissues histology and bronchoalveolar lavage fluid (BALF) protein were assayed. Serum IL-6, lung superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The expression level of NF-κB and ICAM-1 (including immunohistochemical analysis and western blot analysis) were also measured. Results: Lung tissue injury induced by IIR was obviously observed through pathology and BALF protein. MPO activity, IL-6 level and ICAM-1 expression were significantly increased with the elevation of NF-κB, simultaneously, SOD activity was decreased. With Treatment of curcumin, pathology and BALF protein of lung tissue were improved clearly. Inflammatory indexes (MPO activity, IL-6 level and ICAM-1) were improved and antioxidant index (SOD activity) was enhanced paralleled with NF-κB. Conclusion: Using curcumin effectively prevented IIR-induced lung injury. Anti-inflammatory and antioxidant effects of curcumin could be observed by inhibiting the pathway of NF-κB.     

Curcumin prevents the non-alcoholic fatty hepatitis via mitochondria protection and apoptosis reduction

Background: Non-alcoholic fatty hepatitis (NASH) is highly prevalent, mitochondria damage is the main pathophysiological characteristic of NASH. However, treatment for mitochondria damage is rarely reported. Methods: NASH model was established in rats, the protective effects of curcumin were evaluated by histological observation; structure and function assessments of mitochondria; and apoptotic genes expression. Results: NASH rats treated with curcumin displayed relatively slight liver damage when compared with NASH livers. The average mitochondrial length and width of NASH (12.0 ± 3.2 and 5.1 ± 1.1 micrometers) were significantly longer than that of normal (6.2 ± 2.1 and 2.1 ± 1.5 micrometers) and NASH treated with curcumin (7.4 ± 1.2 and 3.2 ± 1.5 micrometers) rats. The average malondialdehyde (MDA) and 4-hydroxy nonyl alcohol (HNE) levels in liver homogenates of NASH rats (4.23 ± 0.22 and 19.23 ± 2.3 nmol/Ml) were significantly higher than these in normal (1.32 ± 0.12 and 3.52 ± 0.43 nmol/mL) and NASH treated with curcumin (1.74 ± 0.11 and 4.66 ± 0.99 nmol/mL) rats. The expression levels of CytC, Casp3 and Casp8 of the NASH livers were significantly higher than normal and NASH treated with curcumin rats livers. Conclusion: Our data demonstrated that curcumin prevents the NASH by mitochondria protection and apoptosis reduction and provided a possible novel treatment for NASH.