Search

Ibrutinib might improve the efficacy of anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cell therapy in chronic lymphocytic leukemia (CLL). We studied the possibility and mechanism of the synergistic effect of ibrutinib and CAR‐T cells in other types of lymphoma. In this study, we selected the CD19 CAR‐T cells of a patient with lymphoma who failed in his CD19 CAR‐T‐cell therapy and a dose of 8 mg/kg/d ibrutinib. Subcutaneous and tail vein tumorigenic mice were established with Raji cells. The differences in the synergistic effect between these 2 models were compared by bioluminescence imaging (BLI) monitoring and flow cytometry (FCM). The expression of the STAT‐3 signaling pathway was assessed by western blot analysis. There was no synergistic effect of ibrutinib and CD19 CAR‐T cells in vitro. Programmed cell death‐ligand 1 (PD‐L1) was expressed in 0.23 ± 0.06% of Raji cells. In the subcutaneous tumorigenic model, the luciferase signal was reduced significantly in the group receiving ibrutinib combined with CD19 CAR‐T cells. Moreover, the proportion of CD19 CAR‐T cells was higher in the polytherapy group than in the CAR‐T‐cell monotherapy group. However, we did not get an analogous synergistic effect in the tail vein tumorigenic model. STAT‐3 signaling pathway expression in the residual tumor cells did not differ between those with and those without ibrutinib, suggesting that the IL‐10/STAT‐3/PD‐L1 pathway was not involved in the synergistic effect. Therefore, some other mechanism might be a target for ibrutinib. Our results provide evidence for the use of ibrutinib in polytherapy for other types of B‐cell lymphoma., Our results might indicate that no IL‐10/STAT‐3/PD‐L1 pathways were involved in the synergistic effect. Then some other mechanism in the microenvironment might be a possible target for ibrutinib. We expect our results would provide evidence for the use of ibrutinib in polytherapy for other types of B‐cell lymphoma.

Although haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) has achieved similar survival to HLA-identical sibling donor (ISD) transplantation, the delayed hematopoietic engraftment as well as higher incidence of graft-versus-host-disease (GVHD), results in prolonged hospitalization, higher costs, and increased morbidity. In this study, a prospective, non-randomized clinical study was designed to evaluate the outcomes of patients who underwent HID HSCT supported by cord blood or ISD HSCT. Between May 2017 and November 2020, 113 patients were enrolled to undergo HID HSCT supported by cord blood (n=88) or ISD HSCT (n=25). The cumulative incidence of neutrophil and platelet engraftment at 30days was comparable in these two groups. Importantly, there was no significant difference in the cumulative incidence of grade II-IV aGVHD at 100days (20.5% [95% confidence interval [CI]: 12.2%–28.8%] versus 12.0% [95% CI: 0.2%–23.8%], P = 0.32) and cGVHD at 1 year (19.5% [95% CI: 11.2%–27.8%] versus 16.6% [[95% CI: 1.3%–31.9%] P = 0.70) between the two groups. Among the HID and ISD groups, the 2-year disease free survival was 76.8 and 80.0% ( P = 0.83), the 2-year overall survival was 82.4 and 88.0% ( P = 0.66), the 2-year GVHD-free, relapse-free survival was 68.9 and 75.3% ( P = 0.62), respectively. Our results indicate that HID transplantation supported by cord blood may offer a good alternative to ISD HSCT for patients with hematopoietic malignancies. Trial registration: Effect of co-infusion third party umbilical cord blood stem cells on haploidentical hematopoietic stem cell transplantation https://www.chictr.org.cn Reg. No. ChiCTR-OIN-17011426.

A patient with relapsed mantle cell lymphoma (MCL) showed stable disease after receiving ibrutinib therapy as a salvage therapy, after the failure of his first chimeric antigen receptor (CAR)-T 19 cell therapy.The combined effects of CAR-T 19 cells from the patient and ibrutinib on JeKo-1 cell were explored in vitro and in vivo.The expression of programmed death-1 (PD-1) receptor on CD3+ T cells in the peripheral blood decreased from 82.95% in the first CAR-T 19 cell therapy to approx. 40% after 14 months of ibrutinib therapy. When the disease progressed again during the ibrutinib therapy, the patient was enrolled into the same clinical trial of CAR-T 19 cell therapy.The efficacy of CAR-T 19 cells increased after the ibrutinib therapy. The mRNA expression level of PD-1 in CAR-T 19 cells after ibrutinib therapy was lower than in CAR-T 19 cells before the ibrutinib therapy. Nevertheless, CAR-T 19 cell therapy combined with ibrutinib had no synergistic effect in a short term in vitro and in the JeKo-1 cell mouse model.We expect our results to provide evidence for the combination treatment of ibrutinib for MCL or even other types of B-cell lymphomas. Moreover, the improvement in CAR-T 19 cell function was based on long-term ibrutinib therapy.

Ovarian cancer is one of the most fatal gynecological cancers. For most ovarian cancer patients, nutritional risk or malnutrition may accompany them for life. Regular nutritional risk screening, timely nutritional assessment and necessary nutritional treatment play an extremely important role in the process of comprehensive treatment of ovarian cancer. The nutritional status and influence of ovarian cancer patients, preoperative screening and assessment of nutritional risk, preoperative and postoperative nutritional treatment indicate that nutritional treatment of ovarian cancer is one of the key factors in the treatment of cancer. We have summarized the status and progress of nutritional support therapy for ovarian cancer. We are aimed to improve the understanding of the impact of nutritional support therapy for ovarian cancer and to guide the clinical work.

Previous study indicated that co-infusion of cord blood cells may potentially improve the outcome of haploidentical donor (HID) transplantation. In this study, we analyzed the outcomes of patients who underwent HID transplantation supported by cord blood when compared with HLA-matched unrelated donor (URD) transplantation. Starting in 2015, 40 patients with hematopoietic malignancies underwent HID transplantation and 26 patients underwent URD transplantation. Hematopoietic recovery, the incidences of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was comparable in the two groups. At two year, the relapse risk in HID group was significantly lower than in URD group (RR 4.630; 95%CI, 1.081-19.839

Ovarian cancer is a predominant gynecologic malignancy and correlated with high mortality and severe morbidity. Exosomal microRNAs (miRNAs) play crucial roles in various processes during the progression of ovarian cancer, such as cell proliferation, apoptosis, and invasion. However, the function of exosomal miR-21-5p in ovarian cancer is still unknown. Here, we found that miR-21-5p was upregulated in ovarian cancer tissues, plasma exosomes of ovarian cancer patients, and exosomes from ovarian cancer cells. MiR-21-5p was incorporated in the exosomes from the ovarian cancer cells. In addition, 5-ethynyl-2'-deoxyuridine (Edu), a marker of cancer cell proliferation, was enhanced by miR-21-5p mimic while reduced by miR-21-5p inhibitor in ovarian cancer cells. MiR-21-5p mimic could increase, but miR-21-5p inhibitor could decrease the migration and invasion of cancer cells. Ovarian cancer cell apoptosis was induced by miR-21-5p inhibitor. Moreover, miR-21-5p inhibitor could up-regulate the expression of pro-apoptotic cleaved caspase3 and Bax while downregulate the expression of anti-apoptotic Bcl2 in the cells. Exosomal miR-21-5p inhibited the expression of cyclin-dependent kinase 6 (CDK6) by targeting its 3'-untranslated region (3'-UTR) at both the mRNA and protein levels. Tumorigenicity analysis in nude mice revealed that exosomal miR-21-5p could increase tumor volume, size, and weight of ovarian cancer in vivo. Besides, miR-21-5p targeted CDK6 in tumor tissues of nude mice. In conclusion, exosomal miR-21-5p contributes to the progression of ovarian cancer by regulating CDK6. Our findings will provide novel insights into the mechanism of exosomal miR-21-5p in the development of ovarian cancer. Exosomal miR-21-5p may serve as a potential target for the therapy of ovarian cancer.

A new benzylated alkamide

Background Glabridin (GLA), a major component extracted from licorice root, has anti-inflammatory and antioxidant activities, but few studies report its mechanism of inhibition of angiogenesis. This study was an extension of our previous work, which demonstrated that GLA suppressed angiogenesis in human breast cancer (MDA-MB-231 and Hs-578T) cells. Breast cancer is one of the most common malignant diseases in females worldwide, and the major cause of mortality is metastasis that is primarily attributed to angiogenesis. Thus, anti-angiogenesis has become a strategy for the treatment of breast cancer. Methods Cell viability of different concentration treatment groups were detected by Cell Counting Kit-8 assay. The expression of several related genes in the Wnt1 signaling pathway in MDA-MB-231 and Hs-578T cells treated with GLA were measured at both the transcription and translation levels using quantitative real-time PCR analyses and western blotting. Immunofluorescence assay analyzed the nuclear translocation of β-catenin. The microRNA-inhibitor was used to knockdown microRNA-148a (miR-148a) expression. Angiogenic potentials of breast cancer cells were analyzed by enzyme-linked immunosorbent assay (ELISA) and tube formation in vitro. Results GLA attenuated angiogenesis by the suppression of miR-148a-mediated Wnt/β-catenin signaling pathway in two human breast cancer cell lines (MDA-MB-231 and Hs-578T). GLA also upregulated the expression of miR-148a in a dose-dependent manner, miR-148a, which could directly target Wnt-3′-untranslated regions (UTRs), and decreased the expression of Wnt1, leading to β-catenin accumulation in the membranes from the cytoplasm and nucleus. Downregulation of miR-148a contributed to the reduction of GLA-induced suppression of the Wnt/β-catenin signaling pathway, the angiogenesis and vascular endothelial grow factor (VEGF) secretion. Conclusions Our study identified a molecular mechanism of the GLA inhibition of angiogenesis through the Wnt/β-catenin signaling pathway via miR-148a, suggesting that GLA could serve as an adjuvant chemotherapeutic agent for breast cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3298-1) contains supplementary material, which is available to authorized users.

Objectives Transfusional iron overload is of major concern in hematological disease. Iron-overload-related dyserythropoiesis and reactive oxygen species (ROS)-related damage to hematopoietic stem cell (HSC) function are major setbacks in treatment for such disorders. We therefore aim to investigate the effect of iron overload on hematopoiesis in the patients and explore the role of ROS in iron-induced oxidative damage in hematopoietic cells and microenvironment in vitro. Patients and methods The hematopoietic colony-forming capacity and ROS level of bone marrow cells were tested before and after iron chelation therapy. In vitro, we first established an iron overload model of bone marrow mononuclear cells (BMMNC) and umbilical cord-derived mesenchymal stem cells (UC-MSC). ROS level, cell cycle, and apoptosis were measured by FACS. Function of cells was individually studied by Colony-forming cell (CFC) assay and co-culture system. Finally, ROS-related signaling pathway was also detected by Western blot. Results After administering deferoxamine (DFO), reduced blood transfusion, increased neutrophil, increased platelet, and improved pancytopenia were observed in 76.9%, 46.2%, 26.9%, and 15.4% of the patients, respectively. Furthermore, the colony-forming capacity of BMMNC from iron overload patient was deficient, and ROS level was higher, which were partially recovered following iron chelation therapy. In vitro, exposure of BMMNC to ferric ammonium citrate (FAC) for 24 h decreased the ratio of CD34+ cell from 0.91 ± 0.12% to 0.39 ± 0.07%. Excessive iron could also induce apoptosis, arrest cell cycle, and decrease function of BMMNC and UC-MSC, which was accompanied by increased ROS level and stimulated p38MAPK, p53 signaling pathway. More importantly, N-acetyl-L-cysteine (NAC) or DFO could partially attenuate cell injury and inhibit the signaling pathway induced by excessive iron. Conclusions Our study shows that iron overload injures the hematopoiesis by damaging hematopoietic cell and hematopoietic microenvironment, which is mediated by ROS-related signaling proteins.

The adverse effects of iron overload have raised more concerns as a growing number of studies reported its association with immune disorders. This study aimed to investigate alterations in the immune system by iron overload in patients with myelodysplastic syndrome (MDS) and an iron-overloaded mouse model. The peripheral blood from patients was harvested to test the effect of iron overload on the subsets of T lymphocytes, and the level of reactive oxygen species (ROS) was also evaluated. The data showed that iron-overloaded patients had a lower percentage of CD3+ T cells and disrupted T cell subsets, concomitant with higher ROS level in lymphocytes. In order to explore the mechanism, male C57Bl/6 mice were intraperitoneally injected with iron dextran at a dose of 250 mg/kg every 3 days for 4 weeks to establish an iron-overloaded mouse model and the blood of each mouse was collected for the analysis of the T lymphocyte subsets and T cell apoptosis. The results showed that iron overload could reduce the percentage of CD3+ T cells and the ratio of Th1/Th2 and Tc1/Tc2 but increase the percentage of regulatory T (Treg) cells and the ratio of CD4/CD8. We also found that iron overload induced the apoptosis of T lymphocytes and increased its ROS level. Furthermore, these effects could be partially recovered after treating with antioxidant N-acetyl-l-cysteine (NAC) or iron chelator deferasirox (DFX). Taken together, these observations indicated that iron overload could selectively affect peripheral T lymphocytes and induce an impaired cellular immunity by increasing ROS level.

To evaluate the long-term efficacy of microwave ablation in the treatment of small renal cell carcinoma (RCC).We retrospectively analyzed 140 cases of small cell renal carcinoma (151 lesions with a mean diameter of 2.8±0.8 cm) treated between April, 2006 and October, 2015 with ultrasound-guided microwave ablation with cooled-shaft needle antenna. One microwave ablation antenna was used for tumors less than 2 cm in diameter and 2 antennas were used for larger tumors. The patients received enhanced ultrasound and CT/MRI examinations at 1, 3, and 6 months after the operation and every 6 months thereafter. The overall survival, disease-free survival, and local tumor progression rate of the patients were evaluated.The response rate of treatment (complete ablation at one month on enhanced images) was 100% in these patients. The local tumor progression rates at 1, 3, and 5 years were 0.9%, 2.0%, and 7.1%, respectively, and the 1-, 3-, and 5-year distant metastasis rates were 1.6%, 2.5%, and 7.9%, respectively. The overall survival rates of the patients at 1, 3, and 5 years were 98.4%, 94.8%, 89.5%, respectively, with disease-free survival rates of 98.4%, 93.0%, and 83.1%, respectively. No major complications occurred in these cases, and multivariate analysis showed that the tumor number (P=0.015) and tumor growth patterns (P=0.049) were independent risk factors that adversely affected the long-term outcome after surgery.Our data show that microwave ablation is a safe and effective modality for treatment of renal cell carcinoma.

To analyze the clinical features of elderly patients with polythemia vera (PV).Statistical analyses were performed for the clinical features of 68 PV patients of age≥60 years and 72 PV patients of age60 years from January 2009 to December 2013 in our hospital.Compared with younger patients, elderly patients with PV had higher incidences of thrombosis (54.4% (37/68) vs 30.6% (22/72), P=0.004), more risk factors of cardio-cerebrovascular (63.2% (43/68) vs 36.1% (26/72), P=0.001), higher white blood cell counts ((13.9±3.8)×10(9)/L vs (7.8±2.2)×10(9)/L, P=0.000) and higher JAK2 V617F allele burden (62% (30%-81%) vs 41% (26%-63%), P=0.035). There was higher incidences of vascular complications in elderly patients with PV (54.4% (37/68) vs 30.6% (22/72), P=0.004). Myelofibrosis transformation occurred with higher frequency in elderly patients with PV (11.8% (8/68) vs 2.8% (2/72), P=0.039). And there was no significant difference in the frequency of leukemia transformation between elderly patients and younger patients (4.4% (3/68) vs 0 (0/72), P=0.112). There was higher mortality rate in elderly patients with PV (14.7% (10/86) vs 4.2% (3/72), P=0.032).There are more risk factors in elderly patients with PV. The elderly patients with PV has high risk to complicat with thrombosis and transformated to myelofibrosis and leukemia. Prevention or delay of these complications is currently the goal of treatment, so that it could reduce the mortality rate and disease progression.

In breast cancer, the cancer stem cells (CSCs) are thought to be the main cause of metastasis and recurrence. Targeting of CSCs or cancer cells with stem cell-like properties has become a new approach for the treatment of breast cancer. Glabridin (GLA), a phytochemical from the root of Glycyrrhiza glabra, exhibited effective antitumor properties in various human cancer cells. However, the roles of GLA in the regulation of CSC-like properties and the underlying molecular mechanisms remain unclear. Here, we reported that GLA attenuated the CSC-like properties through microRNA-148a (miR-148a)/transforming growth factor beta (TGFβ)-SMAD2 signal pathway in vitro and in vivo. In MDA-MB-231 and Hs-578T breast cancer cell lines, GLA enhanced the expression of miR-148a through DNA demethylation. By targeting of the SMAD2-3'-UTR, miR-148a blocked the expression/activation of SMAD2, and in turn, restored the epithelial characteristics, adhesive abilities, and CSC-like properties. Furthermore, in mouse xenograft models, we also confirmed that GLA attenuated the tumor growth, mesenchymal characteristics, and CSCs-like properties via demethylation-activated miR-148a. Our findings suggested a potential treatment strategy to reduce the CSCs-like properties, and therefore enhance the effectiveness of breast cancer therapy.

To screen the plasma microRNA (miRNA) profile of immune thrombocytopenia (ITP) patients.Agilent 19.0 miRNA microarray was used to detect the expression profile of miRNA in plasma from 25 ITP patients and 20 healthy controls from June 2012 to September 2013. The software programs of TargetScan and miRanda were used for predicting target genes associated with differential miRNA. Then gene ontology (GO) and pathway analysis were performed to explore the genes and pathways involved in the pathogenesis of ITP. And differential miRNA was validated by real-time quantitative polymerase chain reaction (PCR).A genome-wide miRNA array revealed 29 differential miRNAs in the plasma samples of ITP patients including 15 up-regulated and 14 down-regulated miRNA. A total of 608 potential genes were predicted by TargetScan and miRanda.GO result showed that there were 475 (78.12%), 491(80.76%) and 533 (87.66%) genes respectively involved in biological process, molecular function and cellular component.Enrichment test showed 9 GO terms had significant difference (P0.05). Pathway analysis showed that 157 pathways were associated with 608 genes.Enrichment test showed 25 pathways had significant difference (P0.05). As revealed by real-time PCR, the expressions of miRNA4778-5p and miRNA4800-5p became obviously up-regulated while those of miRNA4707-5p, miRNA4721, miRNA3620-3p and miRNA378i decreased (all P0.05). The results agreed with those of microarray.The plasma differential miRNA profiles are identified in ITP patients. And miRNA is involved in calcium signaling pathway and T cell receptor signaling pathway may be associated with ITP pathogenesis.

Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related mortality worldwide. Current standard practices for treatment of HCC are less than satisfactory because of metastasis and recurrence. In addition to treating acute promyelocytic leukemia (APL), arsenic trioxide (As2O3) also suppresses other solid tumors, such as HCC. However, the effects of As2O3 on the migration/invasion potential of liver cancer cells and the molecular mechanisms underlying in remain unclear. Here we found that As2O3 attenuated the migration/invasion potential of HCC cell lines by blocking matrix metalloproteinases (MMPs) activities and inducing a mesenchymal to epithelial transition (MET). Indeed, As2O3 elevated the expression of microRNA-491 (miR-491) via demethylation. On one hand, as a target miRNA of MMP9, miR-491 decreased the MMP9 expression. On the other hand, miR-491 blocked the activation of nuclear factor κB (NF-κB), which transcriptionally inactivated MMP2 and induced a MET (as determined by the increased expression of E-cadherin and decreased expressions of snail, slug, and vimentin). Knockdown of miR-491 abolished the As2O3-induced MMPs inactivation, MET, and the migration/invasion potential of HCC cell lines. By understanding a novel mechanism how As2O3 inhibits the migration/invasion potential of liver cancer cells, our study may help to identify potential therapeutic targets for liver cancer.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Current standard practices for treatment of HCC are less than satisfactory because of cancer stem cells (CSCs)-mediated post-surgical recurrence. For this reason, targeting the CSCs or the cancer cells with CSCs-like properties has become a new approach for the treatment of HCC. GLA exhibits anti-tumor effects in that it attenuates the proliferation, migration, invasion, and angiogenesis of human cancer cells. However, the functions of GLA in the regulation of CSCs-like properties in HCC cells, and the molecular mechanisms underlying in remain obscure. Here we found that GLA attenuated the CSCs-like properties by the microRNA-148a (miR-148a)-mediated inhibition of transforming growth factor beta (TGF-β)/SMAD2 signal pathway in HCC cell lines (HepG2, Huh-7, and MHCC97H). Indeed, GLA inhibited the activations/expressions of both TGFβ-induced and the endogenous SMAD2. Further, GLA improved the expression of miR-148a in a dose/time-dependent manner. MiR-148a, which targeted the SMAD2-3′UTR, decreased the expression and function of SMAD2. Knockdown of miR-148a abolished the GLA-induced inhibition of TGF-β/SMAD2 signal pathway and the CSCs-like properties in HCC cells. Our study found a novel mechanism that GLA inhibits the CSCs-like properties of HCC cells by miR-148a-mediated inhibition of TGF-β/SMAD2 signal pathway, which may help to identify potential targets for the therapies of HCC.

Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, however, regarding its anti-metastatic effects. The microRNA-200c (miR-200c), which is frequently lowly expressed in triple negative breast cancers (TNBCs), inhibits metastasis by inducing the mesenchymal to epithelial transition (MET). Here, we report that As(2)O(3) attenuates the migratory and invasive capacities of breast cancer cells, MDA-MB-231 and BT-549. Notably, As(2)O(3) induces an MET in vitro and in vivo, as determined by the increased expression of the epithelial marker, E-cadherin and decreased expressions of mesenchymal markers, N-cadherin and vimentin. Moreover, As(2)O(3) up-regulates the expression of miR-200c through demethylation. Over-expression of miR-200c enhances the expression of E-cadherin and decreases the expressions of N-cadherin and vimentin. Further, in MDA-MB-231 cells exposed to As(2)O(3), knockdown of miR-200c blocks the As(2)O(3) -induced MET. Finally, in MDA-MB-231 and BT-549 cells exposed to As(2)O(3), knockdown of miR-200c decreases the As(2)O(3) -induced inhibition of the migratory and invasive capacities. By identifying a mechanism whereby As(2)O(3) regulates miR-200c and MET, the results establish the anti-migration/invasion potential of arsenic trioxide.

To explore effect of iron overload on the proliferation and apoptosis of mesenchymal stem cell(MSCs) and the possible mechanism.Iron overload model of MSCs was established by adding ferric ammonium citrae (FAC) into the culture medium at different concentrations (100, 200, 400 Μmol/L) and incubated for different lengths of time (12, 24, 48 h). The levels of labile iron pool (LIP) and reactive oxygen species (ROS) were measured to confirm oxidative stress state in the model. Changes in cell proliferation and apoptosis after iron overload were measured through population double time(DT)and annexin V-PI assay. Finally, the expressions of phosphorylated p38 mitogen activated protein kinase (P-p38MAPK), p38MAPK, protein kinase B (AKT), and p53 were determined through Western blot analysis to investigate which ROS-mediated signaling pathway was involved in this process.The LIP level of MSCs was significantly increased by FAC treatment at 400 Μmol/L (mean fluorescence intensity 482.49±20.96 vs. 303.88±23.37, P0.05). The level of intracellular ROS was positively correlated with the concentration of FAC and reached a peak level when cultured with 400 Μmol/L FAC (P0.05).After treatment with 400 Μmol/L FAC at different time points (12 h, 24 h, and 48 h), the DT of MSCs was (1.47± 0.11) d, (1.80±0.13) d, and (2.04±0.14) d, respectively, which was signifcantly longer than that of the control, which was(1.20±0.05)d (P0.05).The apoptosis rate was also significantly higher in iron overload group[(3.51±1.17)% vs.(0.66±0.62)%, P0.05]with consequent increase in the expressions of P-p38MAPK, p38MAPK, and p53 proteins in iron overload group, while no significant difference was found in the expression of AKT.Iron overload can inhibit the proliferation of MSCs and induce their apoptosis through the generation of ROS, which is probably due to the stimulation of p38MAPK- p53 signaling pathway.

To evaluate the mortality trend of chronic obstructive pulmonary disease (COPD) among residents in Liaoning province during the period of 1984-2010.The cut-points were ascertained by Monte Carlo Permutation test in COPD mortality trend lines of Poisson regression with Joinpoint Regression Program. The annual percent changes (APC) before and after the cut-points and the average annual percent change (AAPC) of COPD mortality were examined during the period.Significant declining trends on COPD mortality among the urban population during 1984-2010 and that of rural population during 1999-2009 were found. The standardized urban COPD mortality rate by Chinese population declined from 243.93 per 100 thousand in 1984 to 33.13 per 100 thousand in 2010. The urban 26 years AAPC was -5.8%. While the mortality in the rural population decreased from 251.33 per 100 thousand in 1999 to 102.25 per 100 thousand in 2009 in the same population. The rural 10 years' AAPC was -6.8%. The total trend of COPD mortality reduction was mainly resulted from the fast decline of bronchitis mortality. The AAPC of COPD mortality of the urban population was -9.0% and greater than that of the rural population (-6.8%) from 1999 to 2009. The urban population had a lower COPD mortality than that of the rural population. In urban area, males had a higher COPD mortality than females, however, in the rural area, males had a lower COPD mortality than the females.The COPD mortality among the residents of Liaoning province declined significantly from 1984 to 2010. Further studies are needed to confirm the viewpoint of WHO that the prevalence of COPD would have a continuous increasing trend in China.

To investigate the in vitro effect of iron overload on the generation of reactive oxygen species (ROS) and of bone marrow (BM) cell function.BM mononuclear cells (BMMNCs) were cultured with ferric citrate (FAC) at different concentrations and for different time to create iron overload and confirmed by the detection of cellular labile iron pool (LIP). The changes of ROS, apoptosis, hematopoietic colony formation (CFU-E, BFU-E, CFU-GM and CFU-mix) and the percentage of the CD34 + cells percentage were analyzed. The differences of these index were tested after the iron overload treated with deferasirox (DFO) or antioxidants (N-acetyl-L-cysteine, NAC).1) When BMMNCs were cultured with FAC, the LIP was found to increase in a time and concentration dependent manner. The intracellular LIP reached maximum at 400 micromol/L of FAC for 24 hours. 2) The ROS of total cells, leukocytes and erythrocytes increased to 1.77, 1.75 and 2.12 fold respectively compared with that of normal control when cells were cultured at 400 micromol/L of FAC for 24 hours . DFO and NAC could reduce the ROS efficiently (P0.05). 3) The apoptotic rates of the FAC treated cells [(24.80 +/- 2.99)%] increased significantly compared with that of normal control [(8.90 +/- 0.96)%]. The capacity of hematopoietic colony formation in FAC treated cells decreased markedly compared with that of normal control (P0.05). The percentage of CD34+ cells of FAC treated cells [(0.39 +/- 0.07)%] also decreased significantly compared with that of normal control [(0.91 +/- 0.12)%]. And these changes could be recovered by addition of NAC or DFO.Iron overload can affect the hematopoiesis by inducing the generation of ROS and this damage could be corrected by removing the excess iron and ROS of the BM cells. These findings might improve the treatment of dyshematopoiesis in patients with iron overload.

To establish a model of hematopoietic stem and progenitor cells with iron overload derived from umbilical cord blood (UCB) cells and explore the effects of reactive oxygen species (ROS) on the hematopoiesis of hematopoietic stem and progenitor cells with iron overload.The model was established by adding different concentrations (50, 100, 200, 400 µmol/L)of ferric citrate (FAC) into mononuclear cells from UCB and culturing for different times (6, 12, 24 h). The UCB cells were divided into 4 groups: control group, group FAC, group FAC+N-acetyl-L-cysteine (NAC) and group FAC+ L-Glutathione (GSH). Then the changes of ROS, labile iron pool (LIP), apoptosis, the capacity of hematopoietic colony forming (CFU-E, BFU-E, CFU-GM, CFU-mix) and the percentage and the numbers of CD34(+), CD33(+), GlyA(+) cells were detected. And the changes of these indices were tested after the treatment of iron overload UCB with antioxidants (NAC and GSH).UCB cells were cultured with the addition of FAC at different concentrations for different times. The level of total ROS increased in time and concentration-dependent manners. The intracellular level of ROS peaked when cultured at 200 µmol/L of FAC for 24 hours. Cells were treated with antioxidants NAC or GSH after cultured with 200 µmol/L FAC for 24 hours. Then the ROS levels of total cells, myeloid cells and erythroid cells decreased markedly versus normal controls. The LIP of total cells, myeloid cells and erythroid cells increased markedly when cells were cultured at 200 µmol/L of FAC for 24 hours versus normal controls (P0.05). NAC and GSH had no effect on the level of LIP. The apoptotic rates of FAC-treated cells [(20.90 ± 3.45)%] increased significantly versus normal controls [(9.20 ± 1.29)%] (P0.05). The capacity of hematopoietic colony forming in FAC treated cells decreased markedly versus normal controls. The percentage and numbers of CD34(+), CD33(+), GlyA(+) cells of FAC-treated cells also decreased significantly versus normal controls (P0.05). And these changes could be recovered by the addition of NAC or GSH.Oxidative stress plays an important role in the injuries of hematopoiesis of hematopoietic stem and progenitor cells with iron overload by inducing the generation of ROS. These findings may help us find a specific target and improve the therapeutic efficacy of ineffective hematopoiesis in patients with iron overload.

This study was aimed to detect the expression of leukemia stem/progenitor cell (LSPC) related genes (ABCB1, BMI-1, HOXB4) in the patients with acute leukemia, and to explore its clinical significance in acute leukemia. Bone marrow samples were collected from de novo acute leukemia patients (41 cases), patients with complete remission (CR, 16 cases) and the patients with non-malignant hematologic diseases (10 cases) respectively. And the expressions of ABCB1, BMI-1, HOXB4 genes were detected by comparative real-time quantitative PCR (RQ-PCR) with SYBR Green assay. The results showed that the expressions of ABCB1, BMI-1, HOXB4 were not detected in the patients with non-malignant hematologic diseases, but were higher (relative expressive level: 4.26 ± 2.26, 3.72 ± 1.91, 3.74 ± 2.38) in de novo acute leukemia patients and lower (relative expressive level: 2.14 ± 1.47, 2.07 ± 0.99, 1.47 ± 0.89) in the acute leukemia patients with CR (p0.05). The expressions of LSPC related genes were lower (relative expressive level: 1.77 ± 1.29, 2.09 ± 1.26, 1.78 ± 1.49) in the patients acquired CR/partial remission (PR) than those in the patients not acquired CR/PR (relative expressive level: 7.23 ± 1.78, 3.96 ± 0.92, 4.48 ± 2.57) (p0.01). Univariate analysis revealed that there were more cases with the expression of LSPC immunophenotype (CD34(+)CD38(-)CD96(+) and CD34(+)CD38(-)CD123(+)) and more hyperleukocytosis cases in patients with any higher expression of LSPC related gene (p0.05). Analysis of multiple parameters discovered larger significance (p0.01). It is concluded that there is a good relationship between LSPC related genes (ABCB1, BMI-1, HOXB4) and LSPC immunophenotype. The expression of LSPC-related genes is higher in de novo acute leukemia patients, and lower in patients acquired CR/PR. The patients with higher expressed LSPC-related genes display worse response to chemotherapy, lower CR/PR rate and higher leukocytosis, the analysis of multiple parameters may be a good method for assessing the therapeutic efficacy/prognosis of acute leukemia.

This study was to establish an iron overload bone marrow (BM) model by co-culturing the mononuclear cells from BM with iron, and investigate its hematopoiesis changes. The iron overload model was set up by adding different concentration of ferric citrate (FAC) into the mononuclear cells from BM and culturing for different time, and the model was confirmed by detecting labile iron pool (LIP). Then the apoptosis of hematopoietic cells, ability of hematopoietic colony forming (CFU-E, BFU-E, CFU-GM and CFU-mix) and percentage of the CD34(+) cells of the BM cells all were determined. The changes of these indexes were tested after the iron-overloaded BM was treated with deferasirox (DFO). The results showed that after BM cells were cultured with FAC at different concentrations for different time, the LIP increased in time-and concentration-dependent manners. The intracellular LIP reached maximum level when cultured at 400 µmol/L of FAC for 24 hours. The detection of BM cell hematopoietic function found that the apoptotic rate of the FAC-treated cells (24.8 ± 2.99%) increased significantly, as compared with normal control (8.9 ± 0.96%)(p0.01). The ability of hematopoietic colony forming in FAC-treated cells decreased markedly, as compared with normal control (p0.05). The percentage of CD34(+) cells of FAC-treated cells (0.39 ± 0.07%) also decreased significantly, as compared with normal control (0.91 ± 0.12%)(p0.01). And these changes could be alleviated by adding DFO. It is concluded that the iron-overloaded model has been set by adding iron into the mononuclear cells from BM in vitro, and the hematopoietic function of iron-overloaded BM is deficient. These changes can be alleviated by removing the excess iron from the BM cells through treating with DFO. These findings would be helpful to further study the mechanism of iron-overload on the hematopoiesis of BM and also useful to find the way to treat iron-overload patients with hematopoietic disorders.

To analyze the impact of mortality by age and causes of death on life expectancy at birth among residents of Liaoning province.The study included mortality data of urban and rural residents in two periods (1973 - 1975 and 2004 - 2005). Both Abridged Life Table and Arriaga method were used to calculate and to decompose life expectancy changes by age and causes of death.From 1975 - 2005, the life expectancy increased by 4.68 years in urban residents and 4.91 for rural residents with a higher increment among females than males. Most part of the increase (76.27% and 82.81% for urban and rural male, 58.76% and 62.13% for urban and rural female) in life expectancy within the last 30 years could be explained by the decrease of mortality in the populations at age 0 - 4 and 55 - 74. Diseases related to respiratory system and infectious disease were contributing the most to the gap in life expectancy between the two periods. Mortality of heart disease was a negative contributor to the changes in life expectancy among both rural and urban residents while the mortalities of cerebro-vascular diseases and malignant tumors were the negative contributors for rural residents.The increase of life expectancy in the last 30 years was mainly resulted from the decrease of mortality on both respiratory and infectious diseases. Control of chronic diseases is the key point to increase the life expectancy among the residents of Liaoning province.