Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is centrally involved in the control of cell growth, proliferation, differentiation and cell cycle regulation. Recent studies have found that the mTOR pathway is complicated and the dysregulation of mTOR pathway is recognized to be associated with lots of tumors. Several inhibitors of mTOR could inhibit oncogene transformation, growth and angiogenesis of tumors. So far, four inhibitors of mTOR have been tested in clinical trials, and some have been accessed to phase Ⅱ or Ⅲ trial. Therefore, in this review, we discuss the regulators that govern mTOR pathway activity, and highlight clinical results obtained with the first generation of mTOR inhibitors to reach the oncology clinics.

Objective To investigate the correlation between the combination of smoking with CYP2E1-RsaⅠ and GSTT1 genes polymorphisms and pancreatic cancer. Methods The genetic polymorphisms of CYP2E1-RsaⅠ and GSTT1 were analyzed by polymorphism-polymerase chain reaction (PCR) technique in peripheral blood leukocytes of 150 pancreatic cancer cases and 150 non-cancer controls. Results The frequency of CYP2E1-RsaⅠ(c1/c1) and GSTT1(-) was 38.7% and 69.3% in pancreatic cancer cases and 20.7% and 44.7% in healthy controls, respectively. Statistical tests showed significant differences in the frequencies between the two groups (χ~2=15.75, P<0.01; χ~2=18.62, P<0.01). The risk of pancreatic cancer patients with CYP2E1-RsaⅠ(c1/c1) was significantly higher than that of controls (OR=3.19, 95% CI=2.53-4.26). The individuals who carried with GSTT1(-) had a higher risk of pancreatic cancer (OR=2.85, 95% CI=1.92-4.64). Combined analysis of the polymorphisms showed that the percentage of CYP2E1-RsaⅠ(c1/c1)/GSTT1(-) in pancreatic cancer and control groups was 30.7% and 6.7%, respectively (χ~2= 42.39, P<0.01). People who carried with CYP2E1-RsaⅠ(c1/c1)/GSTT1(-) had a higher risk of pancreatic cancer (OR=16.63, 95% CI=8.94-22.01). The smoking ratewas significantly higher in the case group than in the control group (OR=2.74, 95% CI=1.32-4.58, P<0.01), and statistical analysis suggested an interaction between smoking and CYP2E1-RsaⅠ(c1/c1) or GSTT1(-) genotypes polymorphisms which increased the risk of pancreatic cancer (OR=8.84, 95% CI=5. 51-11.62; OR=20.40, 95% CI=4.98-29.53). Conclusion CYP2E1-RsaⅠ(c1/c1) and GSTT1(-) are the risk factors in pancreatic cancer. Smoking is also related to the susceptibility to pancreatic cancer. There may be a synergetic interaction among CYP2E1-RsaⅠ(c1/c1) and GSTT1(-) and smoking on the elevated susceptibility of pancreatic cancer.

Objective To investigate the changes of bone mineral density (BMD) in patients with type 2 diabetes (T2DM) complicated with osteoporosis (OP) and analyze the factors related to diabetic osteoporosis (DOP) so as to provide theoretical evidence for early diagnosis and prevention of osteoporosis complicated with T2DM. Methods According to their BMD values, patients were divided into OP group and non-OP group. Then we compared differences in sex, age, body mass index (BMI), diabetes duration, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin (FIns), insulin sensitivity index (ISI), quantitative of urinary albumin (ALb), quantitative of urinary protein in 24 hours, serum calcium (Ca), phosphorus (P) and alkali phosphatase level (ALP), and made correlation analysis. Results Compared with those in non-OP group, patients in OP group had older age, longer disease course, smaller baric index, lower bone density, higher alkali phosphatase, lower insulin sensitivity index, higher glycosylated hemoglobin, higher quantitative of urinary protein in 24 hours and urinary microprotein, which were significantly different according to t-test (P<0.05). However, the levels of fasting plasma glucose, serum phosphorus and serum calcium did not differ obviously. BMD of type 2 diabetes was negatively correlated to age, disease course, glycosylated hemoglobin, quantitative of urinary protein in 24 hours, ALb and ALP, but positively correlated to BMI and ISI, and had no correlation with serum calcium, serum phosphorus and fasting plasma glucose. Conclusion Many factors, such as older age, low body weight, long duration of the disease, high level of blood sugar, insulin dysfunction, low insulin sensitivity, high serum alkaline phosphatase and diabetic nephropathy, contribute to osteoporosis in T2DM.

Objective To study the effects of cytokines Th1 and Th2 in Class V lupus nephritis (V-LN). Methods Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2 and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10 and IL-13) were simultaneously analyzed using fast quant human Th1/Th2 protein array, and Pearson analysis was used to evaluate the association between cytokines and clinical parameters. Results ① Cytokine profiling: Among the 9 cytokines detected simultaneously by fast quant human Th1/Th2 protein array, the expression of four cytokines was up-regulated obviously, namely, Th1 cytokines (IL-2) and Th2 cytokines (IL-4, IL-10 and IL-13); that of IL-10 was 10 times above the normal control. ② Pearson correlation analysis: There was a positive correlation between IL-10 and SLEDAI (r=0.877, P<0.01), but a negative correlation between IL-10 and hemoglobin concentration (r=-0.856, P<0.01). There was also a negative correlation between IL-4 and 24h urine protein (r=-0.754, P<0.05), between IL-13 and 24h urine protein (r=-0.769, P<0.05). Besides, IL-1 and creatinine were positively correlated (r=0.784, P<0.05). Conclusion There were extensively abnormal Th2 cytokines in V-LN patients, suggesting that anti-Th2 therapy may produce a marked effect on V-LN.

Objective To compare the changes in fibrinogen (Fib), C-reactive protein (CRP) and left atrial (LA) size between patients with atrial flatter (AFL) and those with atrial fibrillation (AF) to explore the relations among them. Methods We selected 53 AF patients (including 16 cases of paroxymal AF, 13 of persistent AF and 24 of permanent AF) and 18 patients with AFL; the control group consisted of 32 cases of sinus rhythm (SR). In all the patients, ECG or Horter and UCG were conducted; Fib and CRP were measured. The levels of the above indexes in AF group, AFL group and subgroups were compared with each other, and with those in the control group. Correlation analysis between CRP and LA size was made. Results Fib, CRP and LA size in AF group were significantly different from those in AFL and SR groups, but did not differ between the latter two groups. So did other parameters among the three groups. CRP in persistent AF and permanent AF differed significantly from that in AFL, SR and paraxymal AF. LA size in the groups of persistent AF differed from that in SR group, but there was no difference between those in persistent AF and AFL groups. LA size in permanent AF was significantly different from that in AF, AFL and SR. Positive significant linear correlations were found between CRP and LA size in AF (r=0.33). Conclusion Hypercoagulable state exists in AF; the AF. Positive correlation exists between LA size and inflammatory reaction; there is no hypercoagulable state in AFL.

ABSTRACT:Objective To investigate CA125 and ALDH1 levels in diagnosis and postoperative follow‐up of endometriosis (EMs) .Methods Serum CA125 and ALDH1 levels were tested by enzyme‐linked immunosorbent assay (ELISA) in 105 patients with EMs and 100 healthy subjects who came to our hospital between January 2011 and June 2013 .Results The preoperative serum CA125 and ALDH1 levels of EMs patients were significantly higher than those in the control group ( P<0 .05) .Serum ALDH1 levels in stages I and II of EMs were significantly higher than those in the control group (P<0 .05) ,but there was no difference in serum CA125 level between the two groups ( P>0 .05) .Taking CA125≥35 U/mL and ALDH1≥2 .0 pg/mL as the boundary values ,the specificity , sensitivity ,positive predictive value and negative predictive value of serum CA 125 combined with ALDH1 for diagnosis of EMs were 87 .1% ,91 .6% ,84 .6% and 89 .3% ,respectively .One month after operation ,serum CA125 and ALDH1 levels of EMs patients were decreased significantly (P<0 .05) ,but they were still higher than those in the control group ( P<0 .05) .Six months after operation ,their serum CA125 and ALDH1 levels did not differ from those in the control group (P>0 .05) .Relapse occurred in 1 patient 1 year after treatment and in 6 patients 2 years after treatment ;all these patients had a higher serum ALDH1 level than the control group ,but only 2 of them had a higher serum CA125 level .Conclusion The combined detection of serum CA125 and ALDH1 has a higher sensitivity in diagnosis of EMs .Serum ALDH1 level increases in stages Ⅰ and Ⅱ and recurrent patients and can become a better serum marker for early diagnosis and detection of the recurrence of EMs in patients .

Objective To study the expression and significance of Ezrin in triple negative breast cancer tissues .Methods We selected 102 cases ,including 24 ones of triple negative breast cancer ,58 ones of non‐triple negative breast cancer ,and 20 of benign breast disease .The expression of Ezrin in all the specimens was detected by SP immunohistochemistry .We observed whether there was any difference between the positive expression rates of Ezrin in the three groups . We also analyzed the correlation between Ezrin expression and clinicopathologic parameters of triple negative breast cancer .Results The positive expression rate of Ezrin in groups of triple negative breast cancer , non‐triple negative breast cancer , and benign breast disease was 15 .00% ,48 .28% and 75 .00% ,respectively . The difference between the three groups differed significantly ( P < 0 .01 ) . The high expression of Ezrin in triple negative breast cancer had relationship with histological grading and clinical TNM staging (P< 0 .05 ) , but not with patients' age , tumor size , or axillary lymph node metastasis ( P > 0 .05 ) . Conclusion Ezrin is highly expressed in triple negative breast cancer tissues ;therefore , it can be used as an important indicator of poor prognosis of triple negative breast cancer .

ABSTRACT:Objective To study the platelet changes in patients with unstable angina with different blood glucose ,and their related biochemical index changes ,and their relationship with global registry of acute coronary events (GRACE) score .Methods For this clinical study ,we enrolled 82 patients diagnosed with unstable angina , 47 of whom were male and 35 were female .Upon admission ,their random blood glucose was tested .According to different blood glucose values ,they were divided into normal blood glucose group (<6 .1 mmol/L) and high blood glucose (≥ 6 .1 mmol/L ) group . The following clinical data were compared between the two groups :age , hypertension ,diabetes ,smoking history ,and BMI .We detected EF (% ) ,HBA1C ,glucose ,LDL‐C ,HDL‐C ,TG , LPA ,CREA ,UA ,hsCRP ,BNP ,CKMB ,CTNI ,D‐Dimer ,and GRACE risk scores .We compared the platelet test results :PLT ,P‐LCR ,PDW ,and MPV .We also detected the relationship of MPV with hsCRP ,D‐Dimers and GRACE risk scores .Results MPV ,hsCRP ,and GRACE risk score differed significantly between normal blood glucose group and high blood glucose group (P<0 .05) .In the latter group ,MPV had significant correlation with hsCRP ,D‐Dimers and GRACE risk score ( r=0 .28 , r=0 .41 , r=0 .56 , P<0 .05) .Conclusion Hyperglycemia in patients with unstable angina causes the increase of MPV , change of the inflammatory marker hsCRP , and increase of clinical GRACE risk score .Abnormal MPV may predict the increased risk of unstable angina in patients with hyperglycemia upon hospitalization .

ABSTRACT:Objective For preparation of vascularized islets , to isolate and culture human adipose derived stem cells , investigate the role of adipose derived stem cells (ADSCs ) in promoting the proliferation and vascularization of human umbilical vein endothelial cells (HUVECs ) co‐cultured in vitro , and explore its mechanism .Methods ADSCs and HUVECs were isolated by collagenase digestion method ,then cultured ,and identified by morphology ,immunofluorescence or multi‐directional differentiation .The co‐culture system of ADSCs and HUVECs was established , HUVECs cultured alone were set up for control group . The proliferation , vascularization and concentration of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b‐FGF)in the supernatant were compared between the two groups .Results The third generational ADSCs had uniform long spindle fiberous morphology and multi‐directional differentiational function . Immunofluorescence test of surface antigens on ADSCs revealed CD44/CD49d (+ ) ,CD31/CD34 (-) ,on HUVECs CD31/vWF (+ ) . High vascular density was found when co‐cultured in Matrigel of ADSCs and HUVECs than alone of HUVECs .Growth curve shown at days 3 , 4 and 5 of the logarithmic phase , HUVECs count in co‐culture group of ADSCs and HUVECs was (4 .52 ± 0 .31) × 104 ,(7 .18 ± 0 .45) × 104 ,and (8 .23 ± 0 .36) × 104 under indirect co‐culture condition , while that in individual HUVECs group was (2 .71 ± 0 .25) × 104 ,(4 .87 ± 0 .26) × 104 ,and (6 .86 ± 0 .33) × 104 ( P<0 .01) .Population doubling time of HUVECs was shorter in co‐culture group than in individual group .Also ,the OD value of HUVECs was higher in co‐culture group than in individual group when cultured at days 1 ,3 ,5 and 7 ( P<0 .01) .When cultured at days 3 ,7 and 13 ,the concentration of VEGF and b‐FGF in the supernatant was higher in co‐culture group than in individual group ( P< 0 .01 ) . Conclusion ADSCs can promote the proliferation and vascularization of HUVECs in vitro co‐culture conditions by secreting or increasing the HUVECs secretion of VEGF and b‐FGF .

Objective To establish the HeLa cell line that can stably express EYFP fluorescent protein as the model for anion channel blocker (halide ion) screening ,which lays the foundation for high throughput screening of anion channel blocker (halide ion) .Methods Through gene recombination technology ,a new lentivirus vector which can express mutant protein YFP (EYFP‐H148Q/I152L) and puromycin resistance ,was built .The mixture of lentivirus vector and packaging plasmid was transfected into 293T cells to produce lentivirus particles . After infection of HeLa cells by the lentivirus particles ,puromycin was used to screen the cells as YFP‐positive HeLa cell line .Then cell amplification was carried out after purification and efficiency of EYFP‐H148Q/I152L was further detected by Real‐time quantitative PCR (RT‐PCR) and Western blot .We then verified the activity of EYFP‐HeLa transfected cell line as a screening model of anion channel blocker .Results Gene sequencing verified that EYFP‐H148Q/I152L was successfully inserted into lentivirus vectors .RT‐PCR and Western blot results showed that the target gene was overexpressed in HeLa cells . The specific yellow fluorescence of EYFP of HeLa cells could be observed under fluorescence microscope with the efficiency of nearly 100% . I- (low permeability ) solution stimulated the opening of anion (halogen) channels ,and the yellow fluorescence was quenched by I - flow into cells . Conclusion The EYFP‐HeLa cell line can stably express EYFP yellow fluorescent protein and is sensitive to the internal flow of I - .Therefore ,it can be used as an ideal screening model of anion channel blocker (halide ion) .