The mitogen activated protein kinases-extracellular signal regulated kinases (MAPK-ERK) pathway is involved in regulation of multiple cellular processes including the cell cycle.In the present study using a Huh7 cell line Con1 with an HCV replicon,we have shown that the MAPK-ERK pathway plays a significant role in the modulation of HCV replication and protein expression and might influence IFN-α signalling.Epithelial growth factor (EGF) was able to stimulate ERK activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 led to an elevated HCV RNA load and higher NS5A protein amounts in Con1 cells.It could be further demonstrated that the inhibition of the MAPK-ERK pathway facilitated the translation directed by the HCV internal ribosome entry site.Consistently,a U0126 treatment enhanced activity of the HCV reporter replicon in transient transfection assays.Thus,the MAPK-ERK pathway plays an important role in the regulation of HCV gene expression and replication.In addition,cyclin-dependent kinases (CDKs) downstream of ERK may also be involved in the modulation of HCV replication since roscovitine,an inhibitor of CDKs had a similar effect to that of U0126.Modulation of the cell cycle progression by cell cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels.Further,the replication of HCV replicon in Conl cells was inhibited by IFN-α.The inhibitory effect of IFN-α could be partly reversed by pre-incubation of Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs.It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes.

Objective To observe the therapeutic effect of anti-inflammatory combined with cedilanid and diuretic therapy for treatment of patients with senile pneumonia and lung cancer accompanied by pleural effusion and to investigate the changes of concentrations in plasma levels of B-type natriuretic peptide(BNP)and C-reactive protein(CRP),procalcitonin(PCT)before and after treatment. Methods From July 2012 to January 2013, a prospective study was carried out to investigate 57 emergently hospitalized patients with pleural effusion,and according to the etiology,they were divided into two groups:a senile pneumonia group(30 cases)and a lung cancer group(27 cases). The same therapeutic measures were taken in the two groups,such as anti-infection,enhancement of cardiac function,diuresis,and limitation of the amount of liquid intake. Respectively,all the patients took the CT scan of the chest before treatment and on the 7th day after treatment,and at the same time,plasma concentrations of BNP,CRP and PCT were detected. Results ①According to the gradation of the New York Heart Association (NYHA),before treatment most of the cardiac function of patients in pneumonia group was at the Ⅲ grade,while that in the lung cancer group was at theⅠgrade,and the incidence of congestive heart failure(CHF)in pneumonia group was significantly higher than that in lung cancer group(86.7% vs. 14.8%,P<0.01). Before treatment,the plasma BNP level in pneumonia group was obviously higher than that in lung cancer group(ng/L:582.67±126.53 vs. 146.27±43.77,P<0.01);compared with that before treatment,BNP was significantly decreased in the pneumonia group(ng/L:225.59±131.33,P<0.05)after treatment,but no such obvious change in the lung cancer group(ng/L:149.34±51.05)was seen. The therapeutic effect of pleural effusion in the pneumonia group was markedly better than that in lung cancer group〔cure:70.0%(21 cases)vs. 0(0),P<0.01〕. ②Before treatment,the plasma levels of CRP and PCT in pneumonia group were remarkably lower than those in lung cancer group(both P<0.05);after treatment,CRP and PCT levels were decreased or decreased to close to the normal physiological range in patients of the two groups,but the comparisons between the two groups there were no statistically significant differences〔CRP(mg/L):20.21±16.32 vs. 22.76±18.53,PCT(ng/L):0.46±0.13 vs. 0.55±0.17,both P>0.05〕. Anti-inflammatory effect in pneumonia group was much superior to that in lung cancer group〔basically cured:86.7%(26 cases)vs. 0(0),P<0.05〕. In pneumonia group,the decrease of the above two indexes after treatment was consistent with the pneumonia shadow dissipation,while in the lung cancer group,no such consistency was found,apparently,the latter phenomenon was associated with the tumor invasive occupation. Conclusion To detect the concentration changes of plasma BNP, CRP and PCT has important clinical significance in screening the cardiac insufficiency and evaluating the curative effect of anti-inflammatory combined with cedilanid and diuretic therapy in patients of lung diseases complicated by pleural effusion.

The woodchuck model is an excellent animal model to study hepadnaviral infection. The new progresses in this model made possible to examine the T-cell mediated immune responses in acute and chronic hepadnaviral infection. Recently, a new assay for cytotoxic T-cells based on detection of CD107 was established for the woodchuck model. In addition, new immunotherapeutic approaches based on combination of potent antiviral treatment and DNA-protein vaccines were proven to be useful for treatment of chronic hepatitis B.

AIM:To investigate the potential role of Sonic hedgehog (Shh) signaling pathways in the radioresistance of esophageal cancer.METHODS:Radioresistant cell line Eca109R was established by repeating X-ray irradiation at dose of 60 Gy in total using Eca109 cells as parental cells.The radiosensitivity of the parental and radioresistant cells was confirmed by colony formation assay.The cell viability was detected by CCK-8 assay.The intracellular protein levels of Shh and Gli1 were determined by Western blot and immunofluorescence.RESULTS:The survival fractions at dose of 2 Gy for Eca109R cells and Eca109 cells were 0.937±0.013 and 0.499±0.042, respectively.The inhibitory rate of cell viability decreased gradually in the Eca109R cells (P<0.05), suggesting that the radioresistant cell line was successfully established.The results of Western blot indicated that the protein expression of Shh and Gli1 was much higher in the Eca109R cells than that in the Eca109 cells (P<0.05).Immunofluorescence staining showed that Gli1 was expressed in the cytoplasm and nucleus, and presented nuclear clustering in the Eca109R cells.The positive rate of Gil1 expression in Eca109 cells was 52.3%± 0.035%, while that in Eca109R cells was 87.6%±0.021% (P<0.05).CONCLUSION:The radioresistance of esophageal cancer may be related to the activation of Shh signaling pathways with over-expression of Gli1 and other related proteins.

OBJECTIVE To explore the systemic prevention messures of ventilator-associated pneumonia(VAP).METHODS Mesures were taken to 54 patients to prevent infection in 54 from 2006 to 2008 and 52 patients with similar symptoms at the same interval time were chosed as control.RESULTS In the test group VAP occurred in 14.81%,with(11.11%) of mortality.In control group VAP accounted for 42.31%,with(26.92%) of mortality.CONCLUSIONS Systemic prevention messures can decrease VAP occurrance.

Alanine Transaminase ; Amikacin ; Anti-Bacterial Agents ; Aztreonam ; Bilirubin ; Carbapenems ; Ceftazidime ; China ; Creatinine ; Cross Infection ; Escherichia coli ; Fibrosis ; Fungi ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Hemorrhage ; Hospitals, Teaching ; Humans ; International Normalized Ratio ; Klebsiella pneumoniae ; Length of Stay ; Leukocyte Count ; Linezolid ; Methicillin-Resistant Staphylococcus aureus ; Mortality ; Multivariate Analysis ; Prevalence ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Vancomycin

Metabolic-associated fatty liver disease (MAFLD) is considered as a multifactorial disease including genetic, physiological, and environmental factors, in which different factors overlap in various pathways, leading to metabolic impairment and liver damage. The main risk factors for MAFLD are overweight/obesity, insulin resistance/type 2 diabetes, hypertriglyceridemia and related dietary behaviors, mainly the intake of fructose beverages. Adherence to the Mediterranean diet is an important predictor of changes in liver fat content in patients with MAFLD. There is increasing evidence that prescribing specific supplements or nutraceuticals that have been proven to have hepatoprotective effects for MAFLD patients can accelerate the improvement of liver enzymes and liver steatosis or might prevent or delay the progression of MAFLD disease.

Abernethy malformation， also known as congenital portosystemic shunts， is rare in clinical practice， with less than 300 cases reported in the global literature up to 2019. The disease can have serious complications such as pulmonary hypertension， liver tumor， and liver failure and tends to have an extremely poor prognosis， and early diagnosis and active and effective treatment can reduce and delay the onset of complications. In this case， portography combined with balloon occlusion helped to display the underdeveloped slender portal vein with dysplasia， so that the child who was formerly misdiagnosed with type Ⅰ Abernethy malformation was diagnosed with type Ⅱ Abernethy malformation， and then the child was successfully treated by transcatheter closure. This article gives a detailed report of this case.