Background and Objective: The expression of transcription factor Elf-1 and inhibitor of apoptosis survivin in non-small cell lung cancer(NSCLC)is correlated with the angiogenic factor vascular endothelial growth factor(VEGF),and are both factors affecting the cell cycle.This study investigated the expression of Elf-1,survivin,and intratumoral microvessel density(iMVD)assessed by monoclonal antibody CD105 in NSCLC,and explored their correlations with clinicopathologic features and angiogenesis of NSCLC.Methods: PowerVisionTM-9000 immunohistochemistry was used to evaluate the expression of Elf-1,survivin,and CD105 in tissue microarrays containing60 specimens of NSCLC and 9 specimens of normal tissue.Western blot analysis was used to evaluate the protein levels of Elf-1 and survivin in 17specimens of NSCLC and 5 specimens of normal tissue.Results: Elf-1 and survivin were detected in 1 of the 9 normal tissues.The positive rates of Elf-1and survivin in NSCLC were 70.0% and 65.0%,respectively.The expression levels of both Elf-1 and survivin were significantly related to tumor differentiation,lymphatic metastasis,clinical stage,and postoperative survival time(P<0.05).Overexpression of both were related to poor prognosis: the survival rates were significantly lower in patients with positive expression than in those with negative expression(P<0.01).Elf-1 expression was positively correlated with survivin expression(r=0.769,P<0.01.Elf-1 and survivin expressions were positively correlated with iMVD(r=0.446,P<0.01 ; r=0.435,P<0.01).Conclusions: The expression of Elf-1 and survivin in NSCLC is related to differentiation,lymphatic metastasis,clinical stage,and prognosis,and both are positively correlated with iMVD.Detection their combined expression can help to predict the malignant behavior of NSCLC.Blocking the activity of Elf-1 and survivin may be a new way to inhibit angiogenesis in NSCLC.

BACKGROUND AND OBJECTIVEThe expression of transcription factor Elf-1 and inhibitor of apoptosis survivin in non-small cell lung cancer (NSCLC) is correlated with the angiogenic factor vascular endothelial growth factor (VEGF), and are both factors affecting the cell cycle. This study investigated the expression of Elf-1, survivin, and intratumoral microvessel density (iMVD) assessed by monoclonal antibody CD105 in NSCLC, and explored their correlations with clinicopathologic features and angiogenesis of NSCLC.

METHODSPowerVision(TM)-9000 immunohistochemistry was used to evaluate the expression of Elf-1, survivin, and CD105 in tissue microarrays containing 60 specimens of NSCLC and 9 specimens of normal tissue. Western blot analysis was used to evaluate the protein levels of Elf-1 and survivin in 17 specimens of NSCLC and 5 specimens of normal tissue.

RESULTSElf-1 and survivin were detected in 1 of the 9 normal tissues. The positive rates of Elf-1 and survivin in NSCLC were 70.0% and 65.0%, respectively. The expression levels of both Elf-1 and survivin were significantly related to tumor differentiation, lymphatic metastasis, clinical stage, and postoperative survival time (P < 0.05). Overexpression of both were related to poor prognosis: the survival rates were significantly lower in patients with positive expression than in those with negative expression (P < 0.01). Elf-1 expression was positively correlated with survivin expression (r = 0.769, P < 0.01). Elf-1 and survivin expressions were positively correlated with iMVD (r = 0.446, P < 0.01; r = 0.435, P < 0.01).

CONCLUSIONSThe expression of Elf-1 and survivin in NSCLC is related to differentiation, lymphatic metastasis, clinical stage, and prognosis, and both are positively correlated with iMVD. Detection their combined expression can help to predict the malignant behavior of NSCLC. Blocking the activity of Elf-1 and survivin may be a new way to inhibit angiogenesis in NSCLC.

Adult ; Aged ; Antigens, CD ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Endoglin ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Microvessels ; metabolism ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; metabolism ; pathology ; Nuclear Proteins ; metabolism ; Receptors, Cell Surface ; metabolism ; Survival Rate ; Transcription Factors ; metabolism

Antibodies, Viral ; blood ; China ; epidemiology ; Female ; Humans ; Immunoglobulin G ; blood ; Male ; SARS Virus ; immunology ; isolation & purification ; Seroepidemiologic Studies ; Severe Acute Respiratory Syndrome ; epidemiology ; virology

BACKGROUNDThere have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.

METHODSThis study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.

RESULTSMedian follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.

CONCLUSIONThe results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Heart Failure ; drug therapy ; Humans ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged

OBJECTIVETo establish the mouse model for the expression of PD-L1 by hydrodynamic injection and to study the effects of myeloablative conditioning on hydrodynamic injection-mediated PD-L1 expression.

METHODSPlasmid amplification, hydrodynamic injection, collagenase perfusion, real time PCR, ELISA and flow cytometry were applied to test the expression and function of PD-L1. Also, animal models were set up to test the effects of chemical or radiactive myeloablative conditioning on hydrodynamic injection-mediated PD-L1 expression.

RESULTSThe expression of PD-L1 mRNA and protein could be detected as early as 8 h after hyrodynamic injection and reached peak expression by 24 h, and returned to baseline level by 7 d after injection. Serum PD-L1 level reached to 100 µg/ml as early as 24 h after injection and plateaued at 7 d after injection. Serum PD-L1 persisted for 3 weeks and declined to baseline after 1 month of hydrodynamic injection. The PD-L1 function induced by hydrodynamic injection was consistent with literature reports. At each time point, the PD-L1 expression was not different significantly between the myeloablative conditioning group and control group; the mice transfected with PD-L1 showed a higher survival rate than that in control group.

CONCLUSIONMyeloablative conditioning does not affect hydrodynamic injection-mediated PD-L1 expression, indicating that the PD-L1 can be used in HSCT mouse model.

Animals ; B7-H1 Antigen ; pharmacology ; Disease Models, Animal ; Flow Cytometry ; Hydrodynamics ; Injections ; Mice ; Myeloablative Agonists ; pharmacology ; RNA, Messenger ; Transfection ; Transplantation Conditioning

OBJECTIVETo explore the risk factors and their differences of metabolic syndrome (MS) on male criminal police, thereby provide the scientific basis to make prevention and control strategies about the metabolic syndrome for the criminal police career.

METHODSBased on physical examination data of criminal police in 2010, 439 patients with MS (CDS) were randomly selected as cases. And as the 1:2 matched nested case-control study, 878 health controls were employed, which were matched with on the basis of sex and age (±1 year). An face-to-face epidemiological investigations on the past exposure status of several possible risk factors was conducted, such as the family history of hypertension and other social economic status, as well as body height and weight, waist circumference, blood pressure, serum lipid and plasma sugar. and the data were analyzed with logistic regression.

RESULTS1317 cases were surveyed, through single factor logistic regression analysis found that 12 factors are related to exposure. Multivariate logistic regression analysis suggested that six factors, such as stress events (OR = 1.989, 95%CI: 1.467∼2.696), snoring (OR = 1.672, 95%CI: 1.218∼2.294), sweets (OR = 0.562, 95%CI: 0.412∼0.766), meat and products (OR = 1.494, 95%CI: 1.065∼2.094), siting after dinner for more than 3 h (OR = 1.399, 95%CI: 1.023∼1.915).

CONCLUSIONSMS has become a important public health problems among criminal police. For their professional special, a series of bad habits , unhealthy life style and psychological problems became important risk factors of MS on criminal police. Targeted prevention and control measures should be taken to reduce the incidence of MS.

Adult ; Case-Control Studies ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Occupations ; Police ; Risk Factors

OBJECTIVETo explore the ratio of lymphocyte subsets in peripheral blood of patients with aplastic anemia (AA) and patients with hypoplastic myelodysplastic syndrome (hypo-MDS) patients and to evaluate their significance.

METHODSThe clinical data of 181 cases of AA and 111 cases of hypo-MDS from January 2008 to December 2014 were collected from Blood Diseases Hospital of Chinese academy of medical sciences, and then the differences of lymphocyte subsets and its effect in 2 groups were analyzed.

RESULTSCD4/CD8ratio, proportion of CD3cells and its subsets CD3CD4/CD3CD8cells in hypo-MDS group were not significant different from AA group (P>0.05). the proportion of CD3CD16/CD56NK cells and CD3CD57T-LGL cells in hypo-MDS group was significantly higher than that in AA group (P<0.05, P<0.01), but CD19B lymphocyte percentage in hypo-MDS patients was lower than that in AA patients (P<0.05). After dividing group according to CD4/CD8ratio, the ratios of CD3CD16/CD56NK cells and CD3/CD57T-LGL cells were higher only in normal CD4/CD8ratio group of hypo-MDS patients than those in AA patients, while the ratio of B lymphocytes was significant different in inverted CD4/CD8ratio group between hypo-MDS and AA patients. The CD19B lymphocyte ratio in hypo-MDS patients was significantly lower than that in AA patients (P<0.05). As well, the levels of erythrocytes and platelets in peripheral blood between hypo-MDS and AA patients only in normal CD4/CD8ratio group were significantly different, while the significant difference of WBC count and reticulocyte ratio were observed in high CD4/CD8ratio and non-inverted CD4/CD8ratio groups, respectively; the significant difference of bone marrow blast ratio and muture monocyte ratio was found in high CD4/CD8ratio group.

CONCLUSIONThe changes of lymphocyte subsets can be used as an reference indicator for differential diagnosis of hypo-MDS and AA. The comparative analysis of patients with these 2 kinds of diseases after dividing into subgroups according to ratio of CD4/CD8cells is beneficial to differentiat diagnosis.

OBJECTIVETo investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML).

METHODSFourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients.

RESULTSAll of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors.

CONCLUSIONThe induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; Azacitidine ; analogs & derivatives ; Cytarabine ; Decitabine ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; Middle Aged ; Remission Induction ; Treatment Outcome

OBJECTIVE: To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis. METHODS: The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed. RESULTS: All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors. CONCLUSION The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.
Aged ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Retrospective Studies ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients with ASXL1 mutation. METHODS: The clinical data of 229 newly diagnosed AML patients treated in our hospital from April 2016 to October 2019 were analyzed retrospectively. The next-generation sequencing technology was used to detect gene mutations in all the patients, the clinical characteristics of the patients with ASXL1 mutation were analyzed. RESULTS: ASXL1 gene mutation was detected out in 45 patients(19.6%). Among these patients, the frameshift mutation (n=22,48.9%) was most common, followed by missense mutation (n=15, 33.3%) and nonsense mutation (n=8,17.8%), respectively, all of them were located at exon 12. The median mutation rate was 32.47%(range, 2.74%-53.50%). The median age of the patients with ASXL1 mutation was 54(range, 14-74) years old, and most of the patients were male, and most of them with the history of MDS or MPN, and low white blood cell count at the initial diagnosed (P<0.05). Patients with ASXL1 mutation showed a lower CR rate than that of without ASXL1 mutation. Patients with or without ASXL1 mutation showed a statistically significant difference in survival at 20 months (P=0.042), while there was no significant difference between the patients in the two groups over 20 months (P=0.505). All the 6 patients with ASXL1 mutation in low-risk group were survived, while the median OS time was 16 months in the high-risk group(P=0.034). Multivariate analysis showed that the history of MDS or MPN and CR rate from induction therapy were the independent risk factors affecting survival of the patients. CONCLUSION Frameshift mutation is commonly in AML patients with ASXL1 gene mutation, and ASXL1 mutation were more often in men, the history of MDS or MPN, and low white blood cell count. The CR rate of the patients with ASXL1 mutation was lower than that of the AML patients without ASXL1 mutations, AML patients with ASXL1 mutation showed poor short-term efficacy, but there was no significant difference between the two groups in long-term survival over 20 months.
Adolescent ; Adult ; Aged ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Male ; Middle Aged ; Mutation ; Prognosis ; Repressor Proteins/genetics* ; Retrospective Studies ; Young Adult