OBJECTIVE To investigate the early events of norcantharidin (NCTD) induced cell apoptosis and cell cycle arrest, the variation of reactive oxygen species (ROS) and the NF-E2-relate? dactor 2/antioxidant response element(Nrf2/ARE) pathway in human HepG2 cells. METHODS The cyto?toxicity was measured by MTT assay. Apoptosis and cell cycle was analyzed by flow cytometry. The intra toxicity ROS production was evaluated by flow cytometry analysis with DCFH-DA probe and the effect of NCTD on Nrf2/ARE pathway was detected by luciferase assay in HepG2C8 cells under the same condition. The mRNA expression of heme oxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase 1(NQO1) antioxidase gene in Nrf2/ARE pathway downstream was evaluated by quantitative real-time PCR. RESULTS No significant cytotoxicity was detected after HepG2 cells were treated with NCTD 30, 60 and 120 μmol · L- 1 for 3 and 6 h, but cellular viability was inhibited significantly by NCTD 30, 60 and 120μmol·L-1 for 24, 48 and 72 h(P<0.01). Cell apoptosis and G2/M phase arrest occurred after HepG2 cells were treated with NCTD 60μmol · L-1 for 12, 24 and 48 h. The percentage of apoptosis increased from (4.00 ± 1.98)%to (12.10 ± 1.70)%for 12 h, from (4.05 ± 0.21)%to (31.8 ± 6.50)%for 24 h, and from (3.90 ± 0.85)% to (33.30 ± 1.41)% for 48 h, respectively. The percentage of G2/M phase increased from (16.51 ± 1.58)% to (40.89 ± 0.18)% for 12 h, from (16.99 ± 1.32)% to (55.29 ± 3.99)% for 24 h, and from (14.45 ± 0.59)% to (50.66 ± 5.88)% for 48 h, respectively. Compared with cell control group, the percentage of G1 phase had a significant decrease in the group with NCTD treated at different time points(P<0.01). No significant change in ROS in HepG2 cells was detected after the treatment with NCTD 30, 60 and 120μmol · L-1 for 3, 6 and 12 h. Nrf2/ARE pathway in HepG2C8 cells was activated by NCTD 30, 60 and 120μmol·L-1 for 6 and 12 h. mRNA expression of HO-1 and NQO1 had a signifi?cant activation in HepG2 cells after treatment with NCTD 30, 60 and 120 μmol · L-1 for 6 and 12 h (P<0.05). CONCLUSION NCTD can activate Nrf2/ARE pathway in the early stage in HepG2 cells, which may inhibit the intracellular ROS production in the early stage. Activation of ROS may not be the main event in NCTD induced HepG2 cell apoptosis and G2/M phase arrest.

Objective Acute coronary syndrome ( ACS) is frequently accompanied by chronic comorbidities , which may se-riously affect its prognosis .This study aims to investigate the value of the Charlson Comorbidity Index ( CCI) in predicting the outcome of ACS by assessing the impact of individual and post-weighted-assignment comorbid conditions of the disease . Methods We retro-spectively analyzed the clinical data on 1 096 cases of ACS treated in Jinling Hospital from January 2010 to March 2014 .We reviewed their general information , clinical presentations , complications , and previous treatments , calculated CCI , and used in-hospital mortali-ty as the index for judging the prognosis . Results Of the 1 096 patients, 73%were males (aged 64.2 ±12.9 years), 27% were females (aged 72.1 ±12.6 years), and 46.8% had comorbidities. Of the diseases included in the CCI system , previous myocardial infarction was the most frequent comorbidity (18.0%), followed by diabetes mellitus ( 14.7%), moderately to severe renal disease (7.1%), cerebrovascular disease (6.0%), and chronic lung dis-ease (6.0%).Single factor analysis revealed statistically significant differences between different CCI groups in such clinical indicators as history of coronary artery disease , history of hypertension , time between symptom onset and admission , hemodynamics , drugs adminis-tered (aspirin, P2Y12 blockers, ACEI/ARB or statins), and reperfusion therapy (P<0.05).Logistic regression analysis showed the strongest predictors of in-hospital mortality were heart failure (OR 1.88, 95%CI:1.57-2.25), metastatic tumor (OR 2.25, 95%CI:1.60-3.19), renal disease (OR 1.84, 95% CI:1.60-2.11), and diabetes mellitus (OR 1.35, 95% CI:1.19-1.19). Receiver operating characteristic curve analysis manifested that either CCI with age or CCI with age and gender was superior to CCI a -lone in predicting in-hospital mortality of ACS patients (AUC 0.761 [95%CI 0.748-0.773] and 0.756 [95%CI:0.743-0.768] vs 0.670 [95%CI:0.656-0.685]). Conclusion Heart failure, diabetes mellitus, renal disease, and metastatic tumors contrib-ute to the in-hospital mortality of ACS patients .CCI together with age and gender may help to assess the prognosis of the disease .

Objective Though paraquat (PQ) is highly toxic, there is still no effective treatment for PQ poisoning .The aim of the article was to study the protective effect and mechanism of the p 38 mitogen-activated protein kinase ( MAPK) inhibitor SB203580 on PQ-induced acute lung injury in rats . Methods 72 SD rats were randomly divided into three groups ( n=24 ): normal saline (NS) group, PQ poisoning group and p38 inhibitor SB203580 intervention (PQ+SB) group.The arterial blood gas analysis, lung wet and dry ratio (W/D),the expression of tumor necrosis factor-α(TNF-α), the superoxide dismutase (SOD) level and the pathological changes of lung tissues were recorded at different time points after drug intervention . Results On the 1st , 3rd, 5th days after drug intervention in PQ group, the alveolo-arterial oxygen partial pressure difference (PA-aO2) [(45.67 ±4.17), (68.78 ±6.63), (80.23 ±7.12 ) mmHg ], the lung tissue TNF-αexpression (14.63 ±3.10], [18.24 ±2.98], [16.22 ±2.79] pg/mg) and W/D ([4.931 ±0.034], [5.020 ±0.064], [5.079 ±0.016]) in-creased gradually to a peak on the 3rd day, while the SOD level de-creased respectively on the 1st , 3rd, 5th days after drug intervention ([175.26 ±7.98], [167.57 ±8.05], [160.24 ±6.78] U/ug) (P<0.05).Compared with PQ group, PQ+SB group got a decrease in the PA-aO2([80.23 ±7.12] vs [44.17 ±4.16]), the lung tissue TNF-αexpression ([16.22 ±2.79] vs [9.48 ±2.72]) and W/D ([4.805 ±0.070] vs [5.079 ±0.016]) (P<0.05), while the pulmonary SOD level increased in comparison with PQ group ([125.89 ±6.65] vs [160.24 ±6.78]) (P<0.05). Conclusion The p38MAPK inhibitor SB203580 plays a certain protective role in PQ-induced acute lung injury by reducing inflammation and improving antioxidant capacity .

Objective To investigate the clinical value of the simple clinical score (SCS) in Emergency Department.Methods A total of 655 patients with critically illness admitted from July 1,2011through August 31,2011 were enrolled to evaluate the clinical application of SCS in emergency rescue room by analysis of the relationship between SCS and outcome of patients,and the correlation between each factor of SCS and the risk of death. Results The higher SCS,the higher hazard ratio for death.Differences in the hazard ratio for death among groups with different scores of SCS were statistical significance ( P ＜ 0.01 ).According to Chi-square test,there were significant differences in each factor ( except body temperature &unable standing or need Home Health Aide) among the groups of SCS ( P ＜ 0.05 ). Binary logistic regression analysis of each factor showed that age,diabetes,coma,pulse,systolic pressure and respiratory rate had significant correlation with patient mortality. After logistic regression analysis,age,diabetes,coma,pulse,systolic pressure and respiratory rate are significantly related to the mortality of patients.Conclusions The SCS scoring system is useful to make a precise evaluation of critically ill patients in the emergency department.When emergency rescue is carried out,particular stress should be focused on age,diabetes,coma,pulse,systolic pressure and respiratory rate.

Objective To explore the effects of intestinal trefoil factor ( ITF) on gastric mucosal epithelial cell proliferation and its possible molecular mechanism . Methods The cultured GES-1 cells were treated with ITF in the concentration of 100 ng/mL and 500 ng/mL in vitro, and then were observed using microscope for the morphological analysis .The Cell Counting Kit-8 ( CCK-8) was used to detect the proliferation activity of GES-1.The cultured GES-1 cells were treated with 100 ng/mL ITF and the specific inhibitor of PI3K/Akt signaling pathway LY294002 (15μmol/L) in vitro, and then were observed using microscope for the morphological analysis . The proliferation activity of treated GES-1cells was detected using CCK-8 and the expressions of p-Akt and Akt of PI3K/Akt signaling pathway were determined by Western blot . Results Compared with the control group , the proliferation activity of GES-1 cells in-creased after being treated with ITF and the higher concentration of ITF induced the higher proliferation activity .LY294002 inhibited the increased proliferation activity of GES-1induced by ITF.The data of Western blot indicated that ITF induced the expression of p -Akt and activated the P3IK/Akt signaling pathway to modulate the proliferation activity of GES -1 cells.However, LY294002 inhibited the PI3K/Akt signaling pathway and then decreased the proliferation activity of GES -1 cells. Conclusion ITF could promote the proliferation ac-tivity of GES-1 cells by activating PI3K/Akt signaling pathway .

Objective:To analyze the clinical characteristics and risk factors of impaired liver and renal function in hospitalized patients with gout.Methods:A total of 494 hospitalized patients with confirmed gout were selected and divided into four groups according to liver and renal function, control(Con), impaired liver function (ILF), impaired renal function (IRF), and both function impaired (ILRF) group. Multivariate logistic regression was used to analyze the risk factors related with impaired liver and renal function.Results:Compared to Con group, ILF group were younger with shorter gout duration, higher body mass index, waist circumference, homeostasis model assessment for insulin resistance (HOMA-IR), serum uric acid, low density lipoprotein-cholesterol (LDL-C), total cholesterol, triglycerides, C reactive protein, higher prevalence of dyslipidemia, obesity, fatty liver, and monosodium urate crystal (MSU) deposition (all P<0.05). IRF group were older and with higher serum uric acid, serum creatinine, C reactive protein, and hypertension, MSU deposition prevalence, with lower prevalence of fatty liver (all P<0.05). Compared to ILF group, IRF group were older, with longer gout duration, lower level of body mass index, waist circumference, HOMA-IR, LDL-C, total cholesterol, triglycerides, lower prevalence of obesity, fatty liver, and higher prevalence of hypertension and type 2 diabetes (all P<0.05). The univariate logistic regression analysis showed that age( OR=0.941, 95% CI 0.906-0.977, P<0.001), serum uric acid ( OR=1.002, 95% CI 1.000-1.005, P=0.043), HOMA-IR ( OR=1.147, 95% CI 1.024-1.285, P=0.018), and MSU deposition ( OR=1.959, 95% CI 1.154-3.326, P=0.013) were the independent risk factors of impaired liver function, while the independent risk factors of impaired renal function were age ( OR=1.104, 95% CI 1.048-1.162, P<0.001), serum uric acid ( OR=1.007, 95% CI 1.004-1.010, P<0.001), and MSU deposition ( OR=2.393, 95% CI 1.191-4.805, P=0.014). Conclusions:Serum uric acid and MSU deposition are the common independent risk factors for impaired liver and renal function in patients with gout. Younger patients with insulin resistance are susceptible to impaired liver function, older patients with hypertension and diabetes are susceptible to impaired renal function.

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase in the downstream of the phosphatidylinositol 3-kinases (PI3K) family. This kinase plays an important role in the development and progression of hepatocellular carcinoma (HCC). Preclinical data demonstrate that 40%-50% of HCC patients have dysregulated expression of the effectors of the mTOR signaling pathway, and the activation of the mTOR pathway is associated with poorly differentiated tumors, early tumor recurrence, and poor survival/prognosis. This article reviews the research advances in the potential role of the mTOR signaling pathway and its inhibitors in the treatment of HCC.