Objective To explore the relevance between lipoprotein(a) and atherosclerotic renal artery stenosis in adults.Methods Literature search was conducted in PubMed and EMBASE Database,using “atherosclerotic renal artery stenosis” as the search term as well as in Wanfang Database,China National Knowledge Infrastructure,and Cqvip Database,using “renal artery stenosis” and “lipoprotein” as the search terms,aiming to find case-control or cohort studies published before 2010.The qualities of all the literatures enrolled were evaluated using Newcastle-Ottawa scale and the data from which were analyzed by the Review Manager 5.0 software.Results Five eligible case-control studies (661 cases) entered the Meta analysis.The results showed that the lipoprotein(a) level was not significantly higher in the case group than that in the control group [ mean difference =0.0702 g/L,95％ CI ( - 0.0688,0.2092),P =0.32 ].Conclusion According to the existing studies,the relevance between lipoprotein(a) and atherosclerotic renal artery stenosis can not be established.

Objective To investingate the effect of low-density lipoprotein (LDL) on epithelial -mesenchymal transition and extracellular matrix (ECM) accumulation in human peritoneal mesothelial cells (HPMCs).Methods (1)HPMCs were randomly divided into control group,LDL group (100 mg/L) and LDL (100 mg/L) + lactoferrin (100 mg/L,LDL receptor blocking agent) group.After co-cultured for 24 h,the expression of LDL receptor in HPMCs was examined by immunofluorescence staining,and the LDL uptake by HPMCs was observed with oil red O staining.(2)HPMCs were cultured with different concentrations of LDL (0,25,50,100 mg/L).After co-cultured for 24 h,the change of cell morphology was observed by inverted phase contrast microscope,and the expression of α-smooth muscle actin (α-SMA) was examined by immunofluorescence.(3) HPMCs were randomly divided into control group (5.6 mmol/L glucose),mannitol group (M,2.18％ mannitol),low glucose group (LG,30 mmol/L),high glucose group (HG,120 mmol/L) and HG + LDL group (120 mmol/L glucose + 100 mg/L LDL).Cocultured for 48 h,the mRNA expression of α-SMA,E-cadherin and type 1 plasminogen activator inhibitor (PAI-1) was detected by real-time quantitative PCR,the protein expression of α-SMA was detected by Western blotting,the content of type I collagen (Col I) and PAI-1 in supernatant was detected by ELISA.Results (1) After co-cultured with LDL for 24 h,the expressin of LDL receptor was found on the cell membrane of HPMCs.Oil red staining showed that LDL could be uptaken into the cells and abolished by LDL receptor blocker.(2) HPMCs tended to be loosely intercellular connected to each ofher,and prsesnted significant formation of fibroblast-like spindle morphology.The cytoplasm immunofluorescence intensity of α-SMA gradually increased with the increase of LDL concentration.Compared to the control group,the expressions of α-SMA mRNA and protein were significantly increased,and the expression of E-cadherin mRNA was decreased in HG + LDL group(all P ＜ 0.05).But the expressions of the parameters above-mentioned were not significant different between HG group and HG + LDL group or between HG group and control group.(3) Compared with HG group or control group,the concentrations of Col Ⅰ [(19.27±0.17) μg/L vs (14.09±0.30) μg/L or (14.81±0.91) μg/L,all P ＜ 0.05] and PAI-1 [(498.24±76.91) ng/L vs (342.19±30.43) ng/L or (220.39±33.82) ng/L,all P ＜ 0.05] in supernatant of HPMCs were significantly up-regulated in HG + LDL group,meanwhile the expression of PAI-1 mRNA was significantly higer than that in control group (P =0.022).Conclusions HPMCs uptake LDL into cells via LDL receptors.LDL can induce HPMCs transdifferentiation in the condition of high glucose,increase the secretion of Col Ⅰ,inhibit the degradation of ECM through up-regulating the expression of PAI-1,and lead to ECM accumulation.

Objective:To evaluate the efficacy and safety of haploidentical(from family member donors) hematopoietic stem cell transplantation(HSCT) for children with hematologic malignancies.Methods: Fifty-eight children under fourteen years with hematological malignancies underwent haploidentical HSCT.All patients had poor-risk clinical or cytogenetic features and reclassified into high-risk and standard-risk groups.Transplantation outcomes were analyzed.Results: Of fifty-eight patient/donor pairs,seven(12.1%) were mismatched in two HLA loci,twenty(34.5%) in three loci,and thirty-one(53.4%) in four loci.Follow-ups were performed for a median of 1 663(752-2 664) days after transplantation.All patients achieved stable engraftments.The cumulative incidence of acute graft-versus-host disease(GVHD) of grades 2-4 was(54.8?7.6)%,and that of grades 3-4 was(11.4?4.8)%.The cumulative incidence of chronic GVHD was(45.6?7.8)% for the total and(19.6?6.5)% for the extensive.Thirty-eight patients survived with a 2-year actual overall rate of survival 59.0% and 78.9% in the high-risk and standard-risk group,respectively.The 3-year probability of LFS was(58.6?8.0)% and(68.4?10.7)%,respectively.Conclusion: The results encourage extending haploidentical HSCT without T-cell depletion treatments to children with an indication for transplantation.

OBJECTIVEThrough comparative study on contents of icariin and total flavonoid of Epimedium acuminatum in different habitats and parts, the distribution and correlation of the two components were observed.

METHODTwenty-four sample spots in four habitats were set up, and the whole plant of these samples was divided as following: leaf, root, stem and rhizome. Total flavonoid and icariin of samples were determined by using the UV method and the HPLC, respectively. The data was analyzed by SPSS 17.0.

RESULTThe distribution of icariin in different parts had the pattern: leaf > root > stem > rhizome, the total flavonoid content was higher in leaf, but it showed no difference in other parts. Habitat had certain effect on icariin accumulation in E. acuminatum. The significant differences of total flavonoid content in E. acuminatum from different parts were not observed.

CONCLUSIONThe distribution of icariin from different parts and habitats has high selectivity. Metabolism and accumulation of flavonoid content in each part have no difference. Flavonoid content is less affected by environment. Considering the distribution of icariin and flavonoid content in every part and the growth strategy in different habitats comprehensively, it is reasonable to harvest the aerial part for the sustainable utilization of E. acuminatum.

Drugs, Chinese Herbal ; chemistry ; metabolism ; Ecosystem ; Epimedium ; chemistry ; metabolism ; Flavonoids ; analysis ; metabolism ; Plant Structures ; chemistry ; metabolism

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1⁺/FLT3-ITD^- increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.

Objective: To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with de novo acute myeloid leukemia (AML) with mutated NPM1. Methods: The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Results: Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78.1%) had normal karyotype, 57 (41.6%) had positive FLT3-ITD mutation, the median NPM1 mutated transcript level at diagnosis was 84.1%. Among the 134 evaluable patients, 115 (85.8%) achieved a complete remission (CR) . Multivariate analyses revealed that WBC<100×10⁹/L (OR=0.3, 95% CI 0.1-0.9, P=0.027) and first induction therapy with "IA10" protocol (OR=0.3, 95% CI 0.1-0.8, P=0.015) were factors associated with achieving a CR. With a median follow-up period of 24 months (range, 2 to 91 months) in 77 survived CR patients, the probabilities of DFS and OS at 3 years were 48.0% and 63.9%, respectively. Multivariate analyses showed that positive FLT3-ITD (HR=3.2, 95% CI 1.6-6.7, P=0.002) , high MRD level after 2 cycles of consolidation chemotherapy (NPM1 mutation transcript level <3-log reduction from the individual baseline, HR=23.2, 95% CI 7.0-76.6, P<0.001) and chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT) rather than allogeneic HSCT (allo-HSCT) (HR=2.6, 95% CI 1.0-6.6, P=0.045) were the unfavorable factors affecting DFS, high MRD level at the time of achieving the first CR (NPM1 mutation transcript level <2-log reduction from the individual baseline, OR=2.5, 95% CI 1.0-6.1, P=0.040) and after 2 cycles of consolidation chemotherapy (HR=4.5, 95% CI 2.0-10.3, P<0.001) were the unfavorable factors affecting OS. Furthermore, DFS and OS rates at 3 years in those receiving chemotherapy or auto-HSCT were 39.7% and 59.1%, respectively; positive FLT3-ITD and high MRD level after 2 cycles of consolidation chemotherapy were independent factors associated with both shorter DFS (HR=3.5, 95% CI 1.6-7.6, P=0.002 and HR=8.9, 95% CI 3.8-20.7, P<0.001) and OS (HR=2.7, 95% CI 1.1-6.9, P=0.036 and HR=3.1, 95% CI 1.2-8.0, P=0.021) ; meanwhile, high MRD level at the time of achieving the first CR associated with shorter OS (HR=3.1, 95% CI 1.2-8.0, P=0.022) . Conclusion Positive FLT3-ITD mutation and high MRD level after induction or consolidation chemotherapy associated with poor outcomes in AML patients with mutated NPM1.

Objective: To explore the significance of minimal residual disease (MRD) in predicting prognosis and guiding therapy of adults with Philadelphia-chromosome negative acute lymphoblastic leukemia (Ph^- ALL) in high-risk. Methods: Data of newly diagnosed adults with Ph^- ALL in high-risk who achieved CR were reviewed. Variables associated with outcome were identified by COX regression model and Landmark analysis. Results: A total of 177 patients, 99 (56%) cases male with a median age of 40 years (range, 16-65 years) were included in this study. Of them, 95 (54%) patients received allo-HSCT in CR₁. Multivariate analyses showed that MRD negativity after the first cycle of consolidation (HR=0.52, 95%CI 0.30-0.89, P=0.017) and achieving CR within 4 weeks (HR=0.43, 95%CI 0.24-0.79, P=0.006) were the factors significantly-associated with longer DFS, and allo-HSCT was associated with both longer DFS (HR=0.13, 95%CI 0.08-0.22, P<0.001) and OS (HR=0.24, 95%CI 0.15-0.41, P<0.001) . Landmark analysis was performed on 121 patients, of 85 patients achieving MRD negativity after the first cycle of consolidation, multivariate analyses showed that MRD negativity after the third cycle of consolidation was significantly-associated with longer DFS (HR=0.18, 95%CI 0.05-0.64, P=0.008) and OS (HR=0.14, 95%CI 0.04-0.50, P=0.003) . For the patients achieving MRD negativity after both the first and the third cycles of consolidation, the 3-year DFS rate in the allo-HSCT cohort had a higher trend compared with that in the chemotherapy cohort (75.2% vs 51.3%, P=0.082) , however, the 3-year OS rates in the 2 cohorts were similar (72.7% vs 68.7%, P=0.992) . In those with MRD positivity after the first and/or the third cycle of consolidation, 3-year DFS (64.8% vs 33.3%, P=0.006) and OS (77.0% vs 33.3%, P=0.028) rates in the allo-HSCT cohort were significantly higher than those in the chemotherapy cohort, and similar to those in the cohort achieving MRD negativity after both the first and the third cycles of consolidation and receiving allo-HSCT. Conclusions MRD negativity after the first cycle of consolidation was a predictor for better outcome in adults with Ph^- ALL in high-risk. The survival advantage of the allo-HSCT cohort was not pronounced compared with that in the chemotherapy cohort even in those with high-risk features but achieving MDR negativity after both the first and third cycles of consolidation. However, allo-HSCT could be a good option for the patients with MRD positivity after the first and/or the third cycle of consolidation.

Objective: To analyze the clinical value of real-time PCR for virus detection in the diagnosis and treatment of patients after allo-HSCT who had no infection evidence of pneumonia using routine pathogen detection panel. Methods: The clinical data of 71 episodes with acute lung injury from May 2015 to March 2017 after allo-HSCT in hematology department of Peking University People’s Hospital (PKUPH) were retrospectively analyzed. PCR for virus detection and other routine pathogen detection tests were performed on bronchoalveolar lavage fluid (BALF) samples. Results: Among 71 episodes with acute lung injury, a total of 15 patients were diagnosed as lower respiratory tract disease merely associated with virus (detection rate of 21.13%) , 19 episodes were absent of lower respiratory tract infection. The median time from allo-HSCT to the occurrence of lung injury were 176 (49-1 376) d and 196 (57-457) d respectively (z=-0.191, P=0.864) . There were no statistical differences for baseline characteristics and clinical features between two groups. The 100-day attributable mortalities were 13.3% (2/15) and 26.3% (5/19) (χ²=0.864, P=0.426) . Patients with low-dose steroids treatment had favorable outcome than those with high-dose steroids treatment (the dose of methylprednisolone ≥250 mg/d as standard) [4.2% (1/24) vs 60.0% (6/10) ]. In patients with detectable virus in BALF, 2 patients died with early high-dose steroids treatment, while 11 patients survived with no steroids treatment or late application. Conclusions Virus infection should be considered in post-HSCT pneumonia patient with negative result using routine pathogen detection panel. Expanding virus detection panel by PCR in BALF could increase diagnostic precision and might be instructive to treatment.

Objective To investigate the prognostic factors of late-onset severe pneumonia ( LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods From January 2009 to December 2015, 68 patients with LOSP after allo-HSCT at Peking University Institute of Hematology were enrolled.In this retrospective study , univariate and multivariate analysis were used to evaluate the prognostic factors for LOSP after allo-HSCT.Results The median time from allo-HSCT to the development of LOSP was 213 ( 90-2330 ) days.The overall survival rate was 42.6% ( 29/68 ) .The median survival time from LOSP to death was 21 days.Early mortality was defined as death within 21 days after LOSP, as late death more than or equal to 21 days.The median oxygenation index was 199.15 (92.21-290.48) mmHg.LOSPs in thirty-two patients (36.8%) were caused by virus, bacteria, fungi or mixed pathogens.The median C-reactive protein (CRP) was 75.65 (0.94-451.00) mg/L.The median procalcitonin ( PCT) was 0.66 ( 0.00 -249.00 ) μg/L.The higher PCT value indicated an early higher mortality rate by the ROC curve (PCT:cut-off≥0.94μg/L).Furthermore, multivariate analysis suggested that PCT more than or equal to 0.94 μg/L was a risk factor for early death of LOSP ( OR=5.77, 95%CI 1.66-20.11, P=0.006).LOSP occurred later or equal to 213 days after allo-HSCT was also a risk factor of early death in LOSP ( OR=4.74, 95%CI 1.33 -16.89, P=0.017 ) .No previous history of chronic graft versus host disease (GVHD) (OR=4.50, 95%CI 1.58 -12.83, P=0.005) and LOSP later or equal to 213 days ( OR=4.40, 95%CI 1.61 -11.99,P=0.004) were the risk factors of late death in LOSP.Conclusions PCT more than or equal to 0.94 μg/L and LOSP later or equal to 213 days are the risk factors of early death in LOSP .No previous chronic GVHD and LOSP later or equal to 213 days are the risk factors of late death in LOSP .

OBJECTIVETo compare the outcomes of patients with adult acute lymphoblastic leukemia (ALL) over the last 14 years by taking 2006 as the demarcation point.

METHODSFrom January 2000 to December 2013, 477 consecutive hospitalized patients with adult ALL were retrospectively analyzed, including 276 (57.9%) with Ph negative B-ALL (Ph⁻-B-ALL) B-ALL, 69 (14.5%) with T-ALL and 132 (27.7%) with Ph positive ALL (Ph⁺-ALL); 111 (23.3%) before 2006 and 366 (76.7%) after 2006. Among 435 patients who achieved complete remission (CR), 248 (57.0%) received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 187 remained on chemotherapy.

RESULTSWith a median follow-up period of 19 months in all patients and 35 months in living patients, overall CR rate was 92.0%. Of 435 CR patients, the cumulative incidences of 5-year relapse, disease-free survival( DFS) and overall survival (OS) rates were 42.5%, 46.2% and 47.6%, respectively. Compared with the patients hospitalized before 2006: ① the Ph+-ALL patients hospitalized after 2006 achieved a higher overall CR rate (P=0.036). There was no difference for CR rates of Ph--B-ALL and T-ALL patients between before and after 2006. ②The CR patients hospitalized after 2006 had higher 5-year DFS and OS rates (P=0.001; P < 0.001), including higher 5-year OS rate in Ph⁻-B-ALL patients (P=0.046), and higher 5-year DFS and OS rates in both T-ALL (P=0.013; P=0.036) and Ph⁺-ALL patients (P=0.003; P < 0.001) , especially in those Ph⁺-ALL patients who received imatinib from the beginning of the induction chemotherapy (P < 0.001; P < 0.001) ③The patients who received allo-HSCT after 2006 had higher 5-year DFS and OS rates (P=0.001; P < 0.001), but there was no difference for the outcomes in those who remained on chemotherapy before and after 2006. After 2006, Ph⁺-ALL patients who received imatinib from the beginning of the induction chemotherapy had the highest 5-year DFS and OS rates compared with Ph⁻-B-ALL and T-ALL patients (P=0.009; P=0.001) . Multivariate analysis showed that allo-HSCT and imatinib were two important factors affecting the outcomes of ALL patients.

CONCLUSIONThe outcomes of ALL patients improved significantly over the last 14 years, especially in Ph⁺-ALL ones.

Acute Disease ; Adult ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; therapeutic use ; Induction Chemotherapy ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Recurrence ; Remission Induction ; Retrospective Studies ; Survival Rate