BACKGROUND: With the optimization of transplantation scheme and the emergence of graft-versus-host disease (GVHD) therapy drugs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recent years has made great progress that makes patients with hematological malignancies have more long-term survival opportunities. OBJECTIVE: To compare the efficiency and safety of three types of allo-HSCT used in the treatment of adults with Philadelphia chromosome (Ph) in acute lymphoblastic leukemia (Ph+ALL).METHODS: A total of 69 patients with Ph+ALL who received allo-HSCT from June 2006 to November 2013 were enrolled, including 23 cases of sib-matched donor transplantation, 24 cases of unrelated-matched donor transplantation, and 22 cases of haploidentical donor transplantation. There were 54 cases of CR1, 13 cases of CR2 to CR3 and 3 cases of relapse. The bone marrow or/and peripheral blood stem cells were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan, cyclophosphamide and total body irradiation. GVHD was prevented by combined use of immunosuppressants including cyclosporine A, short-term methotrexate, mycophenolate mofetil and anti-human thymocyte globulin, etc.RESULTS AND CONCLUSION: The results showed that 68 patients acquired hematopoietic reconstitution, and only 1 case of haploidentical donor transplantation failed. The mean follow-up period was 20.4 months. The acute GVHD incidence of the sibling matched-HSCT, unrelated donor HSCT and related haploidentical allo-HSCT was 30％, 33％ and 45％,respectively; the chronic GVHD incidence (cGVHD) incidence was 22％, 29％ and 36％, respectively; the incidence of aGVHD and cGVHD between groups showed no statistically significant difference. Transplant related mortality (TRM) was 9％, 29％ and 41％, respectively, and there was a significant difference among groups (0.01 < P < 0.05). Recurrence rates were 17％, 21％ and 14％, respectively, and there was no significant difference among groups. The 3-year overall survival rates were 68％, 49％ and 43％, respectively; there were significant differences between sib-matched-HSCT and the other two groups, but no statistically significant difference was found between unrelated donor HSCT and related haploidentical allo-HSCT groups. The 3-year overall survival rate was 58％ for 54 patients in CR1 and 41％ for 15 patients in non-CR1 states. To conclude, the sib-matched HSCT has better effect than unrelated donor transplantation and related haploidentical allo-HSCT; Ph+ALL patients should do transplantation as early as possible in the state of CR1.

The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2 ± 2.02) nm and (238.20 ± 1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein-aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.
Aconitum ; chemistry ; toxicity ; Animals ; Drugs, Chinese Herbal ; toxicity ; Female ; Glycyrrhiza ; chemistry ; toxicity ; Male ; Mice ; Mice, Inbred ICR ; Plant Proteins ; chemistry ; isolation & purification ; toxicity ; Rhizome ; chemistry ; toxicity

OBJECTIVETo investigate the changes of thyroxin and monocyte human leukocyte antigen-DR expression in senior patients with sepsis and explore their clinical significance.

METHODSAccording to the 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions, 125 senior patients with sepsis free of thyroid conditions were divided into non-severe sepsis group (n=86) and severe sepsis group (n=39), with another 30 healthy subjects as the control. Thyroid function was assayed by chemoluminescence method in these patients and monocyte HLA-DR expression was determined by flow cytometry.

RESULTSCompared with the control group and non-severe sepsis cases, the levels of free T3 (FT3), free T4 (FT4), T3, T4 and monocyte HLA-DR expression were significantly lower in severe sepsis cases (P<0.05), but the levels of thyroid stimulating hormone (TSH) were comparable between the 3 groups (P>0.05). The non-severe sepsis cases showed significantly lower levels of FT3, FT4, T3, T4, TSH and monocyte HLA-DR expression than the control group (P<0.05). In severe sepsis group, the levels of FT3, FT4, T3, T4 and monocyte HLA-DR expression showed significant differences between the fatal cases and surviving cases (P<0.05).

CONCLUSIONThe levels of thyroxin and monocyte human leukocyte antigen-DR expression are obviously lower in senior patients with severe sepsis, and their detection may well indicate the severity of the condition and help make prognostic judgment.

Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; HLA-DR Antigens ; blood ; immunology ; Humans ; Male ; Monocytes ; metabolism ; Pneumonia ; complications ; Sepsis ; blood ; etiology ; immunology ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood

OBJECTIVE To explore the clinical and laboratory features of a patient with 8p11 myeloproliferative syndrome (EMS) and CEP110-FGFR1 fusion. METHODS Combined bone marrow cytology, fluorescence in situ hybridization, fusion gene detection was used to analyze the patient. RESULTS Clinically, the patient had many features similar to those with chronic myelomonocytic leukemia, which included hyperleukocytosis, marked eosinophilia, monocytosis, myeloid hyperplasia and hyperplasia. Fluorescence in situ hybridization analysis for FGFR1 gene rearrangement was positive. Further study of the mRNA also confirmed an in-frame fusion between exon 38 of the CEP110 gene and exon 9 of FGFR1 gene. CONCLUSION EMS with CEP110-FGFR1 fusion is a very rare and distinct myeloproliferative neoplasm. FISH and molecular studies may improve its diagnosis.
Cell Cycle Proteins ; genetics ; Chromosomes, Human, Pair 8 ; Female ; Humans ; Middle Aged ; Myeloproliferative Disorders ; genetics ; Oncogene Proteins, Fusion ; genetics ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics

OBJECTIVETo study the infection of human cytomegalovirus (HCMV) and herpes simplex virus type II (HSV-I) and the morphological characteristics of the infected spermatogenic cells in the semen of infertile men.

METHODSWe washed and concentrated the spermatogenic cells obtained from 83 semen samples of infertile men, extracted DNA and then screened HCMV and HSV-II by polymerase chain reaction (PCR). Immunocytochemistry (ICC) was used to detect the expression of correlative virus antigens of the positive semen cells, and the cytology smear was employed to observe the morphological changes of the spermatogenic cells under the microscope after cytology staining.

RESULTSOf all the semen samples, 8 were HCMV positive, 4 HSV-II positive, but none were both HCMV and HSV-II positive. HCMV late antigens were positively and HCMV early antigens negatively expressed in the spermatogenic cells of the 8 HCMV positive cases. In the 4 HSV-II positive cases, 3 were positively and 1 weakly positively expressed. In the semen of the 12 positive cases were found large numbers of immature spermatogenic cells, with different manifestations of apoptosis, such as chromatin pycnosis, vacuoles, damaged nuclear membrane, and apoptotic bodies, but without virus infection-induced specific morphological alteration. Sperm concentration of the positive group was significantly lower than that of the negative (P < 0. 05).

CONCLUSIONSpermatogenic cells infected by HCMV and HSV-II may cause pathologic lesions and affect spermatogenesis. Morphologically, the infected spermatogenic cells may undergo some pathologic alteration, such as apoptosis. The rate of HCMV infection is higher among infertile males with pathologic cells in the semen.

Adult ; Antigens, Viral ; analysis ; Cytomegalovirus ; genetics ; immunology ; Cytomegalovirus Infections ; pathology ; virology ; DNA, Viral ; genetics ; Herpes Simplex ; pathology ; virology ; Herpesvirus 2, Human ; genetics ; immunology ; Humans ; Immunohistochemistry ; Infertility, Male ; pathology ; virology ; Male ; Polymerase Chain Reaction ; Semen ; cytology ; virology ; Spermatozoa ; cytology ; virology

This study was aimed to explore the effect and feasibility of related haploidentical allogeneic hematopoietic stem cell transplantation (hi-HSCT) used in the treatment of patients with Ph⁺ ALL. A total of 22 patients with Ph⁺ ALL received related hi-HSCT from March 2008 to August 2013. The clinical data of all cases were retrospectively analyzed.There were 15 cases of CR1, 3 cases of CR2, 1 case of CR3 and 3 cases of relapse. The bone marrow and peripheral blood stem cells of related haplotype donors were used for transplantation. All patients were subjected to pretreatment consisting of cytarabine, busulfan (Bu), cyclophosphamide and tota1 body irradiation (TBI), etc. GVHD was prevented by combining variety of immunosuppressants including CsA, MTX, MMF and ATG, etc. The results showed that all of 22 patients acquired hematopoietic reconstitution, and the median time of granulocytes exceeding 0.5 × 10⁹/L and platelets exceeding 20 × 10⁹/L which were transplanted by donors were 13 days and 23 days respectively. The mean follow-up period was 13 months. Ten patients had experience of aGVHD, and 8 patients had experience of cGVHD. Two patients died of infection, 3 died of GVHD and 3 died of relapse,and the rest patients were alive in disease-free situation at lase follow-up. The 2-year disease-free surviva1 rate was 57%. It is concluded that related hi-HSCT can prolong disease-free survival of Ph(+)ALL patients and even cure.
Allografts ; Cyclophosphamide ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents ; Neoplasm Recurrence, Local ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Retrospective Studies ; Tissue Donors

Adolescent ; Adult ; Female ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Transplantation, Homologous ; Young Adult

OBJECTIVETo explore efficacy of imatinib for patients with chronic myeloid leukemia(CML) and its resistance-related factors during the treatment.

METHODSThe clinical data of 214 CML patients received imatinib were analyzed respectively in our hospital from April 2005 to December 2010. The therapy history and efficacy of regular follow-up and factors influencing drug resistance were analyzed. COX regression analysis was used to perform the univariate and multivariate analysis.

RESULTSUntil the end of follow up, thirty-one patients (14.5%) occurred drug resistance. One of them was in accelerated phase(AP), and two in blast phase(BP); 69.2% of patients achieved a complete cytogenetic response(CCyR), and 31.3% of patients achieved a major molecular response(MMR). COX analysis was performed in 207 chronic phase(CP) patients. Univariate analysis showed that the course of disease before treatment, the hemoglobin count, the white blood cell count, whether achieved CCyR or not and whether achieved MMR or not were the influencing factors for imatinib resistance. Multivariate analysis showed that whether achieved CCyR or not was the independent factor for drug resistance.

CONCLUSIONWhether achieved CCyR or not is an independent factor and also a protective factor for imatinib resistance in patients with CML.

Adolescent ; Adult ; Aged ; Benzamides ; therapeutic use ; Child ; Child, Preschool ; Drug Resistance, Neoplasm ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase ; drug therapy ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Young Adult

OBJECTIVETo study effects of P311 on the migration of epidermal stem cells (ESCs) in mice with superficial partial-thickness burn and injured cell model in vitro and to explore the mechanism.

METHODS(1) Eighteen male C(57) BL/6 mice were used. Fifteen of them were inflicted with superficial partial-thickness burn on the back. In three injured mice wound tissue and skin of wound edge were obtained at post burn hour (PBH) 6, 12, 24, 48, 72 respectively. The rest three mice were used as normal control, and samples were harvested with the same method as above. The expressions of P311 in harvested samples were assessed with biotin-streptavidin-peroxidase (SP) staining. (2) Six newly born C(57) BL/6 mice were intraperitoneally injected with 50 µg/g BrdU (two times a day) for three days for ESCs-labelling. Seven weeks later, the mice were inflicted with superficial partial-thickness burn on the back. Serial slices of burn wound tissue were prepared at PBH 72 and immunohistochemically stained with SP for observation of the co-localization of BrdU-positive ESCs and P311-positive cells. (3) The empty vector pAdEasy-enhanced green fluorescence protein (EGFP) and the adenovirus P311-expressing vector named pAdEasy-EGFP-P311 were constructed and packed. Human ESCs were isolated by the method of rapid adhesion to collagen IV. After being divided into P311 high-expressing group (n = 3) and EGFP control group (n = 3), the ESCs in two groups were respectively infected by pAdEasy-EGFP-P311 and pAdEasy-EGFP. Scratching assay was performed on ESCs in both groups after they were treated by mitomycin C for 2 hours. The remaining area within the fixed range was measured at post scratching hour (PSH) 0, 24, 48, and 72, and the wound-area healing rate was calculated. Data were processed with independent samples t test.

RESULTS(1) Expression amount of P311 was different in different parts of wound at different time points after burn. Expression amount of P311 in the newly formed epidermis and hair follicle of wound increased along with prolongation of time. Expression amount of P311 in the epidermis and hair follicle of wound edge peaked at PBH 12 and then decreased to normal levels at PBH 72. (2) Co-localization of BrdU-positive ESCs and P311-positive cells was observed in the new epidermal layer of wound tissue of mice, where ESCs were labeled by BrdU. (3) At PSH 48 and 72, wound-area healing rate was obviously higher in P311 high-expressing group [(69 ± 31)%, (89 ± 26)%] than in EGFP control group [(35 ± 12)%, (46 ± 31)%, with t values respectively -2.336, -2.611, P values all below 0.05].

CONCLUSIONSP311 may promote the migration of ESCs both in rats with superficial partial-thickness burns and in injured cell model in vitro, and it may play an important role in wound healing.

Animals ; Animals, Newborn ; Burns ; metabolism ; Cell Movement ; Cells, Cultured ; Disease Models, Animal ; Epidermis ; cytology ; injuries ; Epithelial Cells ; cytology ; metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; metabolism ; Oncogene Proteins ; metabolism ; Stem Cells ; cytology ; Wound Healing

OBJECTIVETo observe the effect of nitric oxide (NO) on adhesion, proliferation, and migration of human epidermal stem cells (ESC) in vitro.

METHODSESC were isolated and cultured by the modified method of rapid attachment to type IV collagen. (1) Morphology of cells was observed under inverted phase-contrast microscope. Expression levels of integrin β(1) and cytokeratin 19 (CK19) of cells were determined by Western blotting and immunofluorescence staining. (2) After being treated with scratching, ESC adhered to the wall was respectively treated with nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) in the concentration of 1, 10, 100, 500 µmol/L. ESC without treatment of SNAP was used as control. The migration rate of ESC was detected at post scratching hour (PSH) 12 and 24. The chemotaxis of ESC (treated with SNAP in above-mentioned concentration) was tested by Transwell assay, and the transferred cell number was counted. (3) ESC was respectively treated with SNAP in the concentration of 10, 100, 500 µmol/L for 1 h. ESC without treatment of SNAP was used as control. The adhesion of ESC was detected with adhesion test, and the inhibition rate of adhesion was calculated. The proliferation of ESC (denoted as absorbance value) was determined by microplate reader at post-treatment hour (PTH) 0, 12, 24, 48. Data were processed with one-way analysis of variance and Dunnett t test.

RESULTS(1) Small clone formed on post culture days (PCD) 5 to 9. On PCD 10 to 14, cell proliferation sped up. CK19 and integrin β(1) were detected to be expressed in the isolated cells. The cells were identified as ESC. (2) Compared with that of ESC without treatment of SNAP [(35.7 ± 0.3)%, (45.7 ± 5.0)%], migration of ESC treated with SNAP in the concentration from 1 to 100 µmol/L was promoted at PSH 12 and 24. Migration rates of ESC treated with 100 µmol/L SNAP were the highest [respectively (48.8 ± 2.7)%, (82.1 ± 15.8)%, with t value respectively 8.34, 5.10, P values both below 0.01]. The number of ESC transferred to membrane after being treated with 100 µmol/L SNAP was significantly larger than that of ESC without treatment of SNAP (t = 9.24, P = 0.00). (3) Absorbance values of ESC treated with 100, 500 µmol/L SNAP were obviously higher than that of ESC without treatment of SNAP (with t value respectively 4.30, 4.67, P values both equal to 0.00). Proliferation of ESC treated with 100, 500 µmol/L SNAP was obviously stronger than that of cells without treatment of SNAP at PTH 24, 48 (with t values from 2.84 to 8.17, P values all below 0.05).

CONCLUSIONSExogenous NO in suitable concentration can promote the migration of human ESC. Exogenous NO can inhibit the adhesion and promote the proliferation of human ESC in vitro.

Cell Movement ; drug effects ; Cell Proliferation ; Cells, Cultured ; Epithelial Cells ; cytology ; drug effects ; Humans ; Nitric Oxide ; pharmacology ; Stem Cells ; cytology ; drug effects