Objective: This article aims to observe the changes in long noncoding RNA (lncRNA) expression profiles in rat hearts after ozone sub-chronic exposure. To provide scientific data to explore the role and mechanism of differentially expressed lncRNA in damaged hearts caused by ozone sub-chronic exposure. Methods: Eighteen Wistar rats were randomly divided into filtered air and ozone exposure groups, with nine rats in each group. The rats in filtered air group were exposed to filtered air, while the rats in ozone exposure group were exposed to ozone at 0.5 ppm(0.980 mg/m³)for 90 days at a frequency of 6 hours per day. After ozone exposure, cardiac tissues were collected and the total RNA was extracted. The expression level of lncRNA in the hearts of two groups was detected by microarray and qRT-PCR method and the potential functions of the differentially expressed lncRNA were analyzed by bioinformatics. Results: Compared with the filtered air group, lncRNA's expression profile was significantly altered in the rat hearts of ozone exposure group. A total of 167 lncRNA were up-regulated significantly and 64 lncRNA were down-regulated significantly. GO analysis indicated that the up-regulated lncRNA might involve in the process of regulating growth and development, and the down-regulated lncRNA might participate in nutrient catabolic. KEGG results showed that the up-regulated lncRNA might be involved in regulating the PI3K-Akt signaling pathway. The down-regulated lncRNA might regulate the metabolic processes of various vitamins and main energy-supplying substances. Conclusion: Ozone sub-chronic exposure can cause changes in the expression profile of lncRNA in rat hearts, which may regulate the effects of ozone sub-chronic exposure on the heart through the metabolism of energy and nutrients.
Animals ; Computational Biology ; Ozone/adverse effects* ; Phosphatidylinositol 3-Kinases ; RNA, Long Noncoding/genetics* ; Rats ; Rats, Wistar

ObjectiveTo investigate the drug-resistant gene polymorphisms in Plasmodium falciparum imported from Equatorial Guinea to Shandong Province. MethodsFrom 2015 to 2016, blood samples were collected from imported P. falciparum malaria patients returning from Equatorial Guinea to Shandong Province, and genome DNA of the malaria parasite was extracted. The drug-resistant Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum were amplified using a PCR assay, followed by DNA sequencing, and the sequences were aligned. Results The target fragments of all 5 drug-resistant genes of P. falciparum were successfully amplified and sequenced. There were 72.8%, 18.6%, and 8.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfcrt gene, respectively, and all mutant haplotypes were CVIET (the underline indicates the mutation site). There were 20.0%, 61.4% and 18.6% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfmdr1 gene, respectively, and the mutant haplotypes mainly included YF and NF (the underlines indicate the mutation sites). There were 1.4%, 98.6%, and 0 of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhfr gene, respectively, and AIRNI was the predominant mutant haplotype (the underline indicates the mutation site). There were 1.4%, 94.3%, and 4.3% of P. falciparum parasites carrying the wild-, mutant-, and mixed-type Pfdhps gene, respectively, and SGKAA was the predominant mutant haplotype (the underline indicates the mutation site). The complete drug-resistant IRNGE genotype consisted of 8.6% of the Pfdhfr and Pfdhps genes, and the K13 gene A578S mutation occurred in 1.4% of the parasite samples. Conclusions There are mutations in the Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and K13 genes of P. falciparum imported from Equatorial Guinea to Shandong Province, with a low frequency in the Pfcrt gene mutation and a high frequency in the Pfmdr1, Pfdhfr, and Pfdhps gene mutations, and the K13 gene A578S mutation is detected in the parasite samples.

OBJECTIVE: To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1). METHODS: The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed. RESULTS: In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188)；RFS (62.5% vs 38.9%) (P=0.166). CONCLUSION Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.
Adult ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Homeodomain Proteins ; genetics ; Humans ; Immunophenotyping ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Recurrence ; Remission Induction

Objective: To investigate the clinic-pathological features, diagnosis and treatment of 8p11 myeloproliferative syndrome (EMS) . Methods: Five patients diagnosed as EMS from Jan 2014 to May 2018 at Blood Disease Hospital, Chinese Academy of Medical Sciences were enrolled. The clinical manifestations, laboratory characteristics, treatment and outcome of these patients were summarized. Results: The peripheral blood leukocyte count of 5 patients with EMS increased significantly, accompanied with an elevated absolute eosinophils value (the average as 18.89×10(9)/L) . The hypercellularity of myeloid cells was common in bone marrow, always with the elevated proportion of eosinophils (the average as 17.24%) , but less than 5% of blast cells. The chromosome karyotype of the 5 cases differed from each other, but presenting with the same rearrangement of FGFR1 gene by fluorescence in situ hybridization technology. The average interval between onset and diagnosis was 4.8 months with a median survival of only 14 months. Conclusion: EMS was a rare hematologic malignancy with poor prognosis and short survival. It was commonly to be misdiagnosed. Analysis of cytogenetics and molecular biology were helpful for early diagnosis.
Chromosomes, Human, Pair 8 ; Eosinophilia/genetics* ; Hematologic Neoplasms/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Lymphatic Diseases/genetics* ; Myeloproliferative Disorders/genetics* ; Receptor, Fibroblast Growth Factor, Type 1/genetics* ; Translocation, Genetic

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions: AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.
Adolescent ; Adult ; Aged ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation ; Histone-Lysine N-Methyltransferase ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Myeloid-Lymphoid Leukemia Protein ; Prognosis ; Retrospective Studies ; Young Adult

Objective: To explore the predictive value of minimal residual disease (MRD) level in Ph-negative precursor B-acute lymphoblastic leukemia (ALL) patients. Methods: De novo 193 Ph-negative B-ALL patients from Sep 2010 to Nov 2017 were involved in the study. The patients' MRD evaluation which can be performed by multiparametric flow cytometry (MFC) after 1 month, 3-month, 6-month treatment. Relapse free survival (RFS) and overall survival (OS) were compared in patients with different MRD level. Results: The median follow-up was 22 months. All patients was evaluated at 497 MRD level. Patients who reach the good MRD level at 1 month (<0.1% or ≥0.1%), 3-month (negative or positive), 6-month (negative or positive) had a significantly higher probability of estimated RFS (74.5% vs 29.9%; 75.6% vs 29.7%; 74.6% vs 11.6%) and of estimated OS (67.5% vs 30.3%; 71.6% vs 27.8%; 74.0% vs 15.7%). Patients who reach the MRD negative at all 3 times had a significantly higher probability of estimated RFS (80.5% vs 30.5%) and better estimated OS (77.1% vs 29.4%) compared to patients with at least MRD failure in one time (P<0.001). Multivariable analysis showed MRD level at 3-month was an independent prognostic factor for DFS and OS. Conclusion: MRD is an important prognosis factor for Ph-negative B- ALL patients.
Flow Cytometry ; Humans ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

OBJECTIVETo investigate the incidence of karyotypes and gene mutations for elder acute myeloid leukemia and to explore the relationship between each other.

METHODSClinical data and bone marrow samples of elder AML patients were collected. Karyotype and gene mutation (FLT3, NPM1, C-Kit, CEBPα, DNMT3A) test were performed, characteristics of karyotypes and gene mutations were analysed.

RESULTSThe incidence of better risk karyotype was 16.6%, in which the incidences of t(15;17), t(8;21) and inv (16)/t(16;16) were 3.90%, 10.73%, and 1.95% respectively; the incidence of intermediate risk karyotype was 72.2%, in which the incidence of normal karyotype was 57.86%; the incidence of poor risk karyotype was 11.20%, in which the incidence of of MLL/11q23, complex karyotype and monosomal karyotype were 1.95%, 6.34%, 5.85% respectively; the incidences of FLT3, NPM1, C-Kit, CEBPα, DNMT3A mutation were 12.57%, 22.06%, 2.16%, 14.71%, 15.71% respectively. Compared with patients older than 60 years, patients with age of 55-60 years were with less complex karyotype (1.09% vs 10.62%)(P=0.003) and monosomal karyotype (2.17% vs 8.85%)(P=0.032), and more t(8;21)(17.39% vs 5.31%)(P=0.008) and inv (16)/t(16;16)(4.35% vs 0.00%)(P=0.045).

CONCLUSIONFor older AML patients, great difference in the distribution of karyotyes was found between the patients older than 60 years and patients with age of 55-60 years, while no such characteristics was found for gene mutations. Good elucidation of karyotypes and gene mutations are key for the treatment of older acute myeloid leukemia patients.

Humans ; Incidence ; Karyotype ; Karyotyping ; Middle Aged ; Mutation ; Proto-Oncogene Proteins c-kit

BACKGROUNDNontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population.

METHODSA nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH.

RESULTSNONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH.

CONCLUSIONSOur findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

Adult ; Age Distribution ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Female ; Femur Head Necrosis ; epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult

OBJECTIVETo explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms.

METHODSPC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of β-catenin. β-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of β-catenin.

RESULTSTreating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations.

CONCLUSIONSuppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphorylation ; Quinazolines ; administration & dosage ; pharmacology ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

OBJECTIVETo explore the relationship between polycyclic aromatic hydrocarbon (PAH) exposure and hepatocellular carcinoma (HCC), and the interaction of PAH exposure and other HCC risk factors to HCC.

METHODSBaseline blood samples, collected from 345 HCC cases and 961 controls, were used to determine the level of PAH-albumin adducts by competitive enzyme-linked immunosorbent assay. Conditional logistic regression analysis was used to assess the effect of PAH-albumin adducts on risk of HCC.

RESULTSThe mean level of PAH-albumin adducts was significantly higher in cases than in controls ((5.68 +/- 0.72) fmol/mg albumin vs (5.46 +/- 0.63) fmol/mg albumin) (u = 5.98, P < 0.01). When compared to subjects in the lowest quantile (< 1.76 fmol/mg albumin), there was an increase in risk of HCC, with adjusted ORs (95%CI) of 1.03 (0.65 - 1.60), 1.18 (0.76 - 1.78), 2.01 (1.42 - 2.82) for subjects in the second (1.76-fmol/mg albumin), the third (15.28-fmol/mg albumin), and the fourth quantile (> 34.21 fmol/mg albumin), respectively (chi(2)(trend) = 15.06, P < 0.01). There was a significant interaction between PAH-albumin adducts and HBsAg, family history of cancer and diabetes mellitus on HCC after adjusted for other risk factors, and relative excess risks due to the interaction (RERI) were 2.50 (u = 3.60, P < 0.01), 0.52 (u = 2.13, P < 0.05) and 0.88 (u = 2.26, P < 0.05), respectively.

CONCLUSIONPAH-albumin adducts was related with HCC, and there is a trend of HCC prevalence increasing with the content of PAH-albumin adducts. There are interactions between PAH-albumin adducts and HBV infection, family history of cancer and diabetes mellitus on HCC.

Adult ; Aflatoxins ; blood ; Aged ; Carcinoma, Hepatocellular ; blood ; epidemiology ; Case-Control Studies ; Causality ; Female ; Humans ; Liver Neoplasms ; blood ; epidemiology ; Male ; Middle Aged ; Polycyclic Aromatic Hydrocarbons ; blood ; Prevalence ; Risk Factors