Aberrant activation of the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB,Akt)-mammalian target of rapamycin(mTOR) pathway is commonly observed in human cancer and is critical for cell survival, proliferation and differentiation.A variety of small molecule inhibitors targeting PI3K-Akt-mTOR pathway are under clinical studies.This review will summarize the recent studies in terms of the PI3K-Akt-mTOR signaling pathway and cancer,research progress of the antitumor activity possessed by PI3K-Akt-mTOR inhibitors,as well as the recent research in the related field conducted by our group.

Objective To investigate the role of three-dimensional speckle tracking echocardiography (3D-STE) in providing a novel approach to assessing myocardial viability in patients with myocardial infarction (MI).Methods The subjects from the Department of Cardiology and the Department of Cardiac Surgery admitted from April 2010 through December 2012 were diagnosed as MI by electrocardiogram,myocardial enzymes and angiography.The clear imaging of angiography was selected out and collected.All patients had different degrees of segmental wall motion abnormalities,and some already had percutaneous transluminal coronary angioplasty and coronary stenting or coronary artery bypass grafting.Patients with diabetes,heart disease and severe valvular disease of heart were excluded.A total of 45 MI patients were checked with routine echocardiography,two-dimensional speckle tracking echocardiography (2D-STE) and 3D-STE.Then,radionuclide myocardial perfusion/metabolic imaging was served as a golden standard to distinguish the viable from nonviable myocardium in each patient within a day.In order to determine the most sensitivity and specificity threshold values of circumferential peak-systolic strain (Cs),longitudinal peak-systolic strain (Ls),radial peak-systolic strain (Rs),3D strain and area strain for viability detection from 3D-STE,the receiver operating characteristic curve was used to investigate the sensitivity and specificity of the detection of viable myocardium with strain parameters in the study.Comparisons between viable and non-viable groups were carried out with t test.Data were expressed as the mean value ± standard deviation (-x ± s).Results The ventricular wall motion abnormality by visual assessment was observed in 368 segments from 720 segments in 45 patients.Furthermore,204 segments were confirmed to be viable by radionuclide myocardial perfusion/metabolic imaging whereas the rest 164 segments were identified as nonviable among 368 abnormal segments.There were no significant differences in circumferential peaksystolic strain (Cs),longitudinal peak-systolic strain (Ls) and radial peak-systolic strain (Rs) by 2D-STE between viable and nonviable group.Compared with those in viable group,there wasn' t any difference in Cs,but Rs and Ls decreased significantly by 3D-STE in nonviable group.The 3D strain and area strain in absolute value decreased in nonviable group compared with viable group.According to 3D-STE,when Rs higher than 11.1％,the sensitivity was 95.1％ and the specificity was 53.4％ for identification of viable myocardium,whereas Ls higher than 14.3％ resulted in sensitivity of 65.2％ and a specificity of 65.7％.Besides,3D strain higher than 17.4％ had a sensitivity of 70.6％ and a specificity of 77.2％ for detection of viable myocardium,while area strain higher than 23.2％ allowed a sensitivity of 91.5％ and a specificity of 78.8％.Conclusions The 3D-STE might have potential reliability of myocardial viability detection in the patients with left ventricular dysfunction after MI.

Lymphocyte subsets in peripheral blood and function of CD4+CD25+ regulatory T cells(Tregs) were assayed in patients during different periods of Graves' disease ( GD ).Breakdown of Tregs' function lead to the wild proliferation of CD4+T lymphocyte,and may play an important role in the pathogenesis of GD.It is difficult to fully restore the Tregs' function to normal after successful medication in Graves' disease,this phenomenon may lead to easy relapse of GD.

Objective To investigate the role of long noncoding RNA-AJ227913 in the pathogenesis of primary gout arthritis (GA). Methods The subjects were divided into three groups:30 acute gout patients (AGA), 30 non-acute gout patients (NAGA), 30 healthy controlsand 30 hyperuricemia patients (HUA). Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to examine the expression of AJ227913 in peripheral blood mononuclear cells(PBMCs) from four groups. 100 μg/ml monosodium urate (MSU) was used to stimulate the peripheral blood of NAGA and healthy controls patients. Then the expression ofAJ227913 was detected by RT-qPCR. Kruskal-Wallis test, Mann-Whitney test, Spearman correlations were used for statistical analysis. Results The expression level of AJ227913 in the AGA group (0.0557 ±0.0156) was higher than that in the NAGA group (0.0223±0.018) and healthy controls group (0.0038±0.0013). There was significant difference between the NAGA group and healthy controls group (P>0.05). Compared with the control group, the expression of AJ227913 in NAGA group which were stimulated by MSU was significantly increased. The Spearman correlation analysis found that the AJ227913 expression levels in GA groups were correlated with UREA (r=0.608, P<0.01), CREA (r=0.337, P<0.05), CYSC (r=0.422, P<0.01). Conclusion Altered expression of AJ227913 may be involved in the inflammatory process of GA and the balance of uricacid.

OBJECTIVETo explore the expression of Bcl-2 mRNA and its effect on prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).

METHODSReal time quantitative PCR was used to determine the expression of Bcl-2 mRNA in 40 PGI-DLBCL patients and 17 healthy controls. The association of Bcl-2 expression with clinicopathological features and prognosis of the patients was analyzed.

RESULTSThe expression level of Bcl-2 mRNA in PGI-DLBCL patients was 1.03 ± 0.93, significantly higher than that of the controls (0.41 ± 0.21) (P < 0.05). The expression of Bcl-2 mRNA in stage IIE-IV patients (1.28 ± 1.01) was significantly higher than that in the stage I-II2 patients (0.62 ± 0.61) (P < 0.05). The expression of Bcl-2 mRNA in patients with international prognostic index (IPI) score >2 (1.95 ± 1.27) was significantly higher than those with IPI score ≤ 2 (0.86 ± 0.75)(P < 0.05). The expression of Bcl-2 mRNA in patients with complete remission (CR) (0.71 ± 0.58) was significantly lower vs. 2.42 ± 0.91 in patients with no CR (P < 0.05). Univariate analysis indicated that β2-MG, IPI score>2, the Lugano staging, and Bcl-2 mRNA expression were associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Multivariate analysis indicated that IPI score>2 was independently associated with OS (P < 0.05), and both IPI score >2 and Bcl-2 mRNA expression were independently associated with PFS (P < 0.05).

CONCLUSIONSThe expression of Bcl-2 mRNA in the tumor tissue of PGI-DLBCL patients is significantly higher than that in controls. PGI-DLBCL patients with higher expression of Bcl-2 have a poor chemotherapy response and inferior prognosis. IPI score >2 and higher expression of Bcl-2 mRNA are independent poor prognostic factors for PFS in PGI-DLBCL patients.

Disease-Free Survival ; Genes, bcl-2 ; Humans ; Lymphoma, B-Cell ; diagnosis ; genetics ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; genetics ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism

Objective To analyze the death characteristics and disease burden of the labor force in Jingzhou City from 2015 to 2018, and to provide a basis for formulating policies to protect the labor force population and propose effective prevention and control measures to reduce the death level and disease burden. Methods The death data of the labor force in Jingzhou City from 2015 to 2018 was collected and statistically analyzed. The death levels, causes of death, and disease burden of the labor force in different years, sexes, ages, and regions were analyzed. Results From 2015 to 2018, the death toll of the labor force accounted for 24.79% of total deaths in Jingzhou City, with a mortality rate of 219.61/100 000 and a standardized mortality rate of 192.17/100 000. There was no significant difference in the mortality rate in different years (P=0.34). The male and female mortality rates were 297.77/100 000 and 139.63/100 000, and the standardized mortality rates were 257.36/100 000 and 119.57/100 000, respectively. The male and female YLL rates were 9.55% and 4.47%, and the standardized YLL rates were 6.75% and 3.12%, respectively. The male mortality and YLL rates were higher than those of the female (P<0.01). The mortality and YLL rate of different age groups increased with age (P<0.01). The mortality rates of urban and rural population were 187.37/100 000 and 229.07/100 000, respectively, the standardized mortality rates were 141.87/100 000 and 208.58/100 000, respectively, the YLL rates were 5.90% and 7.37% respectively, and the standardized YLL rates were 4.13% and 5.20%, respectively. The mortality rate and YLL rate of rural population were higher than those of urban population (P<0.01). The first cause of death in the labor force population was malignant tumor, with the mortality and YLL rate being 87.19/100 000 and 2.90%, respectively. The second cause was injury, with the mortality and YLL rate of 42.60/100 000 and 1.56%, respectively. The leading cause of death was injury in the 15 and 25 years old groups, and malignant tumor in the 35, 45 and 55 years old groups. Lung cancer and liver cancer were the main types of lethal cancers. Transportation accidents and suicide were the main types of lethal injuries. Conclusion The disease burden of the rural labor force was heavy. It is important to strengthen health education for the rural labor force, especially male laborers over the age of 45, and to implement early cancer diagnosis and treatment and injury intervention programs to effectively improve the health of the labor population.

OBJECTIVE To improve the quality standard for Jubei mixture . METHODS The chemical reaction of trinitrophenol and hydrocyanic acid was used to identify Armeniacae Amarum solution . Platycodon grandiflorus ，Fritillaria thunbergii，Scutellaria baicalensis ，the leaves of Eriobotrya japonica and Glycyrrhiza uralensis in Jubei mixture were identified by thin-layer chromatography （TLC）. High-performance liquid chromatography was used to simultaneously determine the contents of four active components ，such as amygdalin ，baicalin，wogonoside and monoammonium glycyrrhizinate in Jubei mixture . RESULTS Trinitrophenol test paper showed brick red . TLC spots of five medicinal materials were clear ，without interference from negative control . The linear ranges of amygdalin ，baicalin，wogonoside and monoammonium glycyrrhizinate were 0.066 8-1.335 5 μg（R2＝0.9994），0.189 8-3.796 9 μg（R2＝0.999 9），0.062 6-1.251 3 μg（R2＝0.999 9），0.041 8-0.835 5 μg（R2＝0.999 8）， respectively. RSDs of precision ，repeatability and stability tests were all lower than 2%. The average recoveries were 98.2%， 99.5%，98.3%，99.6%，and RSDs were 0.7%，1.6%，1.5%，1.1%（n＝6）. The contents of 15 batches of samples were different ， and the content of sample from company A was generally lower than those from companies B and C . CONCLUSIONS The standard established can reflect the inherent quality of Jubei mixture well .

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation