Background: Acute graft?versus?host disease (aGVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo?HSCT). Some studies have found that the presence of certain specific human leukocyte antigen (HLA) loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD. Methods: Totally, 345 consecutive patients undergoing first HLA?matched sibling peripheral blood stem cell transplantation (PBSCT) from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor?recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow?up end?point was 6 months after HSCT. Results:The cumulative incidence of intestinal aGVHD was 19.4%,with 18.0%of the patients classified as classic aGVHD and 1.4% aspersistent, recurrent,or late aGVHD.Multivariate analysis showed that HLA?A31 locus(odds ratio[OR]2.893,95% confidence interval[CI][1.054,7.935], P = 0.039), HLAB40?DR15 (OR 3.133, 95% CI [1.250, 7.857], P = 0.015), and HLAB46?DR9 haplotypes (OR 2.580, 95% CI [1.070, 6.220], P = 0.035), female donor for male recipient (OR 2.434, 95% CI [1.319, 4.493], P = 0.004) were risk factors for intestinal aGVHD. Conclusion: The presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA?identical sibling donors.

OBJECTIVEIn order to figure out how and to what degree the social and economic development and control strategy influencing the epidemics of tuberculosis and to provide reference for tuberculosis prevention and control in China.

METHODSBased on the data from the nationwide random surveys on tuberculosis in 1979, 1984/1985, 1990 and 2000 and the indexes on social and economic development of China, correlation coefficient was used to analyze the relationship of three factors including (1) the change of epidemic situation of tuberculosis from 1979 to 2000; (2) the level of social and economic development; (3) the implementation of Health V Project.

RESULTSThe prevalence rate of smear positive tuberculosis was significantly correlated to per capita net income of rural population, consumption level of city population, per capita GDP, density of population, and proportion of rural population. Among which the correlation with per capita net in come of rural population, consumption level of city population, per capita GDP, or density of population showed negative, correlation but the proportion of rural population showed positive. The range of GDP increase was similar in both areas with or without the implementation of Health V Project from 1990 to 2000 (77.2% and 77.8%). However, the ranges of the decline of prevalence rate were quite different (44.4% and 12.3%) in the two areas. In the western part of China, the range of GDP increase was similar in the areas with or without the implementation of Health V Project. However, the prevalence rate declined in the area that implementing the project but increased in other areas without the project.

CONCLUSIONThe level of social and economic development had influenced the prevalence rate of tuberculosis, but the implementation of tuberculosis control project played an important role in the reduction of tuberculosis prevalence rate from 1979 to 2000 in China.

China ; epidemiology ; Female ; Humans ; Income ; statistics & numerical data ; Male ; Prevalence ; Rural Population ; Socioeconomic Factors ; Tuberculosis ; epidemiology

OBJECTIVEThis study is to understand the difference of semen quality among the different areas and the related factors.

METHODSFive hundred and sixty-two people were under from seven provinces.

RESULTSResults showed that the quantity and density of semen, the rate of moving forward semen, livability, percent age of normal formed semen and the total number of semen were statistically different among the seven areas. The difference was ranged as 28.82%, with the highest 2.95 ml in Shanxi province and the lowest 2.29 ml in Henan province. Geometric mean of semen density was found the lowest 36.27 x 10(6)/ml in Guizhou province, next to it was 42.52 x 10(6)/ml in Shandong province and the highest was 74.77 x 10(6)/ml in Hebei province. The percent age with forward progression of semen was seen the lowest 44.40% in Henan province, followed by 51.88% in Hebei province and 52.88% in Zhejiang province and the highest were 76.50% in Shanghai, 75.24% in Shanxi province, with a range of 72.30%. The highest semen viability was 85.89% in Shanghai, while the lowest 72.35% in Henan, with a range of 18.71%. Normal sperm morphology was seen the lowest 68.45% in Hebei province, with the highest 88.06% in Guizhou province, and the range was 28.65%. The geometric mean of total sperm count was seen the highest 204.23 x 10(6)/ml in Hebei province and the lowest 77.69 x 10(6)/ml in Guizhou province. Results showed through analysis of variance that some indexes were different in some provinces.

CONCLUSIONThe results indicated that the semen quality was different in different regions in China and its influential factors may be region and geography environment.

Adult ; China ; Humans ; Male ; Residence Characteristics ; Semen ; cytology ; physiology ; Socioeconomic Factors ; Sperm Count ; Sperm Motility ; Spermatozoa ; physiology

OBJECTIVEThis study was aimed to observe the efficacy of autologous stem cell transplantation (ASCT) for adult patients with acute lymphoblastic leukemia (ALL), and investigate related prognostic factors.

METHODSA total of 86 adult ALL patients underwent ASCT in Institute of Hematology and Blood Disease Hospital from November 2001 to January 2012 were followed up. Clinical characteristics and outcomes of all patients were retrospectively analyzed. Survival and univariate prognosis were analyzed by the Kaplan-Meier method and multivariate analysis by COX regression model.

RESULTSOutcomes were assessed in 81 cases, including 47 standard-risk and 34 high-risk patients. 1-, 3-, 5-, and 10-year leukemia-free survival (LFS) of standard-risk patients were (82.3±5.7)%, (76.9±6.5)%, (74.1±6.8)%, (67.4±8.9)% respectively,and relapse rates (RR) were as of (13.6±5.2)%, (21.6±6.4)%, (24.5±6.8)%, (31.3±9.0)% respectively. 1-, 3-, 5-, and 10-year LFS of high-risk patients were (55.8±8.9)%, (39.8±9.3)%, (39.8±9.3)%, (39.8±9.3)% respectively, and relapse rates (RR) were (38.8±9.2)%, (56.4±10.0)%, (56.4±10.0)%, (56.4±10.0)% respectively. T-ALL, white blood cell count(WBC) more than 30×109/L when first visited, increased LDH, positive fusion gene of TCR and bone marrow transplantation were the adverse prognostic factors. Multivariate analysis showed bone marrow transplantation was an independent adverse prognostic factor.

CONCLUSIONASCT was a choice for adult ALL patients when suitable donors were unavailable.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Transplantation, Autologous ; Young Adult

OBJECTIVETo evaluate the inhibition effects of DNAzymes specific to Hepatitis B Virus(HBV) s gene and e gene on the expressions of Hepatitis B surface antigen(HBsAg) and Hepatitis B e antigen(HBeAg).

METHODSDNAzymes DrzBS and DrzBC specific to HBV s gene ORF A157UG and e gene ORF A1816UG, respectively, were designed and synthesized. The inhibition effects of DrzBS or DrzBC on the expressions of HBV s and e genes were observed in 2.2.15 cells.

RESULTSThe expression of HBV s or e genes was dramatically depressed after 2.2.15 cells treated by DrzBS or DrzBC. The concentration for effective inhibition was within 0.1-2.5 micromol/L and the inhibition showed a dose dependence within that concentration range. The maximum inhibition was 94.2% and 91.8% for DrzBS and DrzBC, respectively. The inhibition was maintained for 72 hours. The efficiency of inhibiting HbsAg, HbeAg in 2.2.15 cells by DrzBS, DrzBC was higher than that by antisense oligonucleotides for the same target genes. The concentrations for effective inhibition of the DNAzymes were at least 10-fold lower compared with antisense oligonucleotides. Neither inhibition on the replication of HBV DNA nor toxicity to 2.2.15 cells was observed.

CONCLUSIONDrzBS and DrzBC can highly block the expressions of HBV s gene and e gene in 2.2.15 HBV cell model and are proved a specific and effective anti-HBV gene therapeutic means.

DNA, Catalytic ; pharmacology ; therapeutic use ; DNA, Viral ; analysis ; Dose-Response Relationship, Drug ; Gene Expression ; drug effects ; Genetic Therapy ; Hepatitis B ; therapy ; Hepatitis B Surface Antigens ; genetics ; Hepatitis B e Antigens ; genetics

OBJECTIVEScreening for Y chromosomal microdeletions in azoospermia factor (AZF) region with modified multiplex PCR.

METHODS160 cases with spermatogenetic failure were recruited in the experimental group, while 90 cases of donors in controls. According to the laboratory guidelines supported by European Academy of Andrology (EAA) and European Molecular Genetics Quality Network (EMQN), Y chromosomal microdeletions in AZFa, b, c regions were screened with multiplex PCR. The primers of sequence targeted sites (STSs) and conditions of PCR were modified.

RESULTSUsing modified multiplex PCR, 14 (8.75%) cases with Y chromosomal microdeletions were found in the experimental group, while no case in controls. There were 12 cases in AZFc, 1 case in AZFa + b + c, 1 case in AZFb + c. According to statistics, the difference between two groups was significant (P <0.001). Reaction products could be clearly separated with agarose gel and finished in 1 h.

CONCLUSIONModified multiplex PCR protocols supported by EAA and EMQN proved to be very accurate, sensitive and quick, which could be put into screening practice for Y chromosomal microdeletions in AZF region.

Adult ; Chromosome Deletion ; Chromosomes, Human, Y ; genetics ; Genetic Loci ; Humans ; Male ; Polymerase Chain Reaction ; methods ; Seminal Plasma Proteins ; genetics

Objective: To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center. Methods: Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed. Results: A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade Ⅲ-Ⅳ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups. Conclusions: The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.
Graft vs Host Disease ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Middle Aged ; Retrospective Studies ; Siblings ; Unrelated Donors

BACKGROUNDThe postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.

METHODSThe outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.

RESULTSOverall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15 th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).

CONCLUSIONSThis study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.

Adolescent ; Adult ; China ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm, Residual ; mortality ; therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; mortality ; therapy ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Transplantation, Homologous ; Young Adult