Objective To evaluate the safety of mefformin in the treatment of elderly type 2 diabetes mellitus(T2DM). Methods Two hundred and forty-three cases of elderly T2DM hospitalized from Jan.1996 to Dec. 2006 were reviewed; the changes of fasting blood glucose(FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), liver and renal function and blood lactic acid were evaluate before and after treatment. Results The mean time of treatment with mefformin was (6.6±3.9) years (3 months-21 years)in these 243 cases. The levels of FBG, PBG and HbAlc significantly reduced after treatment with mefformin only in 43 cases (17.7%), mefformin combined with other oral hypoglycemic drugs in 124 cases (51.0%) and mefformin combined with insulin in 76 cases (31.3%). There was only 18.1% of the cases with normal range ( > 80 ml/min) of creatinine clearance rate (Ccr), and 25.8% of the cases with Ccr≤50 ml/min. The liver and renal function as well as the blood lactic acid had no significant change after treatment no matter in total cases or in different groups separated by Ccr.Conclusions Mefformin is safety in the treatment of elderly T2DM patients. Ageing is not the contraindication of mefformin. To the patients with high risk, we should monitoring the level of blood lactic acid.

Achyranthes bidentata polysaccharide sulfate (ABPS) was a sulfated derivate derived from Achyranthes bidentata polysaccharide (ABP) which was isolated and identified from Chinese herb Achyranthes bidentata. The anti human immunodeficiency virus type 1 (HIV-1) activities were studied in vitro and in vivo. ABPS was found to inhibit HIV-1 reverse transcriptase and integrase with the 50% inhibiting concentration (IC60) of (2.948 +/- 0.556) micromol x L(-1) and (0.155 +/- 0.030) micromol x L(-1), respectively, but the parent compound ABP was not effective. ABPS inhibited HIV-1 P24 antigen with IC50 of (0.082 +/- 0.044) micromol x L(-1) and selective index (SI) of > (358 +/- 148) in MT-4 cell cultures acutely infected with HIV-1 IIIB virus, and with IC50 of (11.80 +/- 5.90) micromol x L(-1) and SI of > (24.2 +/- 12.1) in PBMC cell cultures acutely infected with clinical isolated zidovudine resistant HIV-1 virus, but there was no activity even at its concentration of 500 micromol x L(-1) in latent infection of H9/HIV-1 IIIB cell cultures. 5% sera taken from rats after intraperitoneal injection from rats with ABPS 125 mg x kg(-1) once or mice with 3 mg x kg(-1) qd for 20 days effectively inhibited HIV-1 P24 in MT-4 cell cultures, but those had no inhibitory effect when given orally. The results suggested that ABPS is a promising HIV-1 inhibitor, active on HIV-1 reverse transcriptase, integrase in vitro and HIV-1 P24 antigens in cell cultures, it was well absorbed by intraperitoneal injection but poor in oral bioavailability. It warrants further study.
Achyranthes ; chemistry ; Animals ; Antiviral Agents ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Female ; HIV Core Protein p24 ; metabolism ; HIV Integrase ; metabolism ; HIV Reverse Transcriptase ; metabolism ; HIV-1 ; drug effects ; enzymology ; Humans ; Immune Sera ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Plants, Medicinal ; chemistry ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; pathology ; virology ; Random Allocation ; Rats ; Rats, Wistar ; Sulfates ; chemistry ; isolation & purification ; pharmacology

OBJECTIVESTo explore the category, quantity and clinical significance of autoantibodies on bone marrow hematopoietic cells in patients with immunorelated cytopenia and evaluate the sensitivity of direct antiglobulin reaction (Coombs test ) of bone marrow mononuclear cells (BMMNC).

METHODSThe category and the positive rate of autoantibodies on bone marrow hematopoietic stem cells, nucleated erythrocytes, granulocytes in 32 patients with uncertain immunorelated cytopenia were investigated by using BMMNC-Coombs test and double immunofluorescence flow cytometry.

RESULTSThe positive rate of autoantibodies on bone marrow hematopoietic cells tested by flow cytometry was 90.63% which was higher than that by BMMNC-Coombs test (50.0%) (p < 0.05). In 29 positive cases, IgG autoantibody accounted for 6.90%, IgM13.8%, IgG+IgA 3.4%, IgG+IgM 31.0%, and IgG+IgM+IgA 44.8%. Of the 29 Patients, 25 (86.2%) with IgG autoantibody, 26 (89.7%) with IgM and 14 (48.3%) with IgA. The patients with IgG autoantibody alone had the lowest hemoglobin levels, and those with IgM autoantibody might have intravascular hemolytic findings. The response time of patients with IgG and IgG+IgM was shorter than that of the other patients. 91.3% of the patients had autoantibodies on bone marrow hematopoietic stem cells and showed pancytopenia, and 50% of the patients had autoantibodies on nucleated erythrocytes and granulocytes. Eleven of 13 patients with negative BMMNC-Coombs tests had autoantibodies on bone marrow hematopoietic stem cells detected by FACS. There was no significant difference of the quantities of the three categories of autoantibodies of nucleated erythrocytes and stem cells. The quantities of IgA on granulocytes were lower than that of IgG and IgM. There was no significant difference between IgG and IgM on granulocytes. The quantity of IgA on hematopoietic stem cells was significantly higher than that on nucleated erythrocytes or granulocytes.

CONCLUSIONSThe sensitivity of double immunofluorescence flow cytometry assay was higher than that of BMMNC-Coombs test for detecting autoantibodies. In immunorelated cytopenia patients, the predominant autoantibody was IgM which could cause intravascular hemolysis, and the second one was IgG which could cause severe anemia. Most immunorelated cytopenia patients had autoantibodies on hematopoietic stem cells and showed pancytopenia. IgA was more easily seen on the hematopoietic stem cells.

Adolescent ; Adult ; Aged ; Autoantibodies ; classification ; metabolism ; Autoimmune Diseases ; immunology ; Bone Marrow Cells ; immunology ; Child ; Coombs Test ; Female ; Flow Cytometry ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Immunoglobulin M ; metabolism ; Male ; Middle Aged ; Pancytopenia ; immunology

OBJECTIVESTo explore the proliferative capacity of bone marrow hematopoietic stem cells and the function of T helper (Th) lymphocytes of patients with immuno-related pancytopenia (IRP).

METHODSTwenty-five untreated IRP patients, 15 IRP patients in complete remission (CR) and 10 normal controls were studied for in vitro yields of CFU-GM, CFU-E and BFU-E from bone marrow mononuclear cells (BMMNC). The mRNA expressions of IL-4, IL-10, IFN-gamma and IL-2 genes in unstimulated BMMNC from 25 untreated IRP patients,15 IRP patients in CR, 19 patients with other hematological diseases presenting pancytopenia and 10 normal controls were detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThere was no significant difference of the yields of CFU-E, CFU-GM or BFU-E among the untreated, and in CR IRP patients and normal controls (P > 0.05). The mRNA expressions of IL-4 and IL-10 of Th2 cells were significantly higher in untreated IRP patients than in the other groups. The mRNA expressions of IFN-gamma and IL-2 of the Th1 cells in all IRP patients were not higher than those in the other groups.

CONCLUSIONSThe cytopenia of IRP patients was not caused by the qualitative abnormality of the hematopoietic stem cells but by the destruction or suppression of hematopoietic stem cells from certain extrinsic insults. The imbalance of Th lymphocytes subtypes and overfunction of Th2 lymphocytes played important roles in the pathogenetic mechanism of IRP leading to increased and overfunctional B lymphocytes, which produced autoantibodies destructing or suppressing hematopoiesis in IRP.

Adolescent ; Adult ; Bone Marrow Cells ; cytology ; Cell Division ; Cells, Cultured ; Child ; Cytokines ; genetics ; Female ; Hematopoietic Stem Cells ; cytology ; Humans ; Male ; Middle Aged ; Pancytopenia ; immunology ; RNA, Messenger ; analysis ; T-Lymphocytes, Helper-Inducer ; physiology

BACKGROUND: Bone morphogenetic protein 2 (BMP-2) has a strong ability to induce and promote the osteogenic differentiation of mesenchymal stem cells. OBJECTIVE: To evaluate the BMP-2 effect on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on an injectable nano-hydroxyapatite/chitosan (nHA/CS) composite scaffold. METHODS: (1) Experiment 1: Passage 3 BMSCs were divided into two groups and cultured with the nHA/CS scaffold or cultured alone. Cell counting kit-8 was used to detect cell proliferation at 1, 3, 5, 7, 14 days of culture. (2) Experiment 2: Passage 3 BMSCs were seeded onto the nHA/CS scaffold and cultured in culture medium containing BMP-2 or not. Alkaline phosphatase activity in cells was detected at 3, 6, 9, 12, 15 days of culture. Cell counting kit-8 was used to detect cell proliferation at 1, 3, 5, 7, 14 days of culture. Alizarin red staining was used to observe the osteogenic differentiation of cells at 1 and 2 weeks of culture. RESULTS AND CONCLUSION: (1) Experiment 1: With the prolongation of culture time, the absorbance values in the two groups were gradually increased, but there was no significant difference between the two groups. At 7 days of culture, the BMSCs adhered tightly to the scaffold surface. (2) Experiment 2: With the prolongation of culture time, the alkaline phosphatase activities in the two groups were gradually increased, and moreover, the alkaline phosphatase activity in the experimental group was higher than that in the control group at different culture time (P < 0.05). The absorbance values in the two groups were also gradually increased, and the value in the experimental group was higher than that in the control group at different culture time (P < 0.05). At 1 and 2 weeks of culture, the number of calcified nodules was higher in the experimental group than the control group. To conclude, BMP-2 has a promotion role in the proliferation and differentiation of BMSCs cultured on the injectable nHA/CS scaffold.

BACKGROUNDPolycythemia vera (PV) is a malignant disorder of hemaopoietic stem cells which is characterized by clonal hyperproliferation and a low rate of apoptosis. This study was to assess endogenous erythroid colony (EEC) formation in the bone marrow of PV patients and determine its clinical significance.

METHODSThe bone marrow mononuclear cells of 26 patients with PV, 2 patients with secondary erythrocytosis (SE), and 19 normal controls were cultured by Marsh's method for EEC evaluation, and the clinical significance was evaluated.

RESULTSEECs appeared in 25 patients with PV but not in 2 patients with SE and 19 normal controls. The number of EECs and the EEC ratio [EEC/erythropoietin (EPO)-dependent colony forming unit-erythroid (CFU-E)] in PV patients positively correlated with hemoglobin (Hb) levels. Their EEC number did not correlate with white blood cell (WBC) counts, platelet (PLT) counts, or leukocyte alkaline phosphatase (LAP) scores. Their EEC did not correlate with serum EPO levels. Fifteen patients with PV were treated with hydroxyurea (Hu) and/or interferon-alpha (IFN-alpha). Their EEC ratio before treatment positively correlated with the treatment time required for complete remission (CR) and negatively correlated with the time before relapse. The EEC numbers of 7 PV patients treated with Hu/IFN-alpha decreased after the blood cell counts dropped to normal levels. There was a positive correlation between the EEC ratio and the incidence of attacks of vascular thrombosis in PV patients. The numbers of apoptosised bone marrow mononuclear cells in PV patients were lower than those in normal controls. The EEC numbers of PV patients negatively correlated with the rate of apoptosis of bone marrow mononuclear cells.

CONCLUSIONSEEC formation is characteristic in PV patients. EEC number in PV patients positively correlates with Hb levels, the time required for CR, and the incidence of attacks of vascular thrombosis. EEC number negatively correlates with the time before relapse. Bone marrow suppressive treatment might decrease EEC number. Thus, EEC number is a sensitive and specific parameter reflecting the abnormal hematopoietic clone burden induced by polycythemia vera. EEC number is an important diagnostic parameter for PV patients.

Adult ; Aged ; Apoptosis ; Colony-Forming Units Assay ; Erythroid Precursor Cells ; physiology ; Erythropoiesis ; Erythropoietin ; blood ; Female ; Humans ; Male ; Middle Aged ; Polycythemia Vera ; blood ; therapy ; Thrombosis ; epidemiology

OBJECTIVETo investigate the growth of endogenous erythroid colony (EEC) in polycythemia vera (PV) patients and its clinical significance.

METHODSBone marrow mononuclear cells of 26 PV patients, 2 secondary erythrocytosis (SE) and 19 normal controls were cultured by Marsh's method for EEC.

RESULTS1. EEC was present in 25/26 (96.2%) PV patients and was not found in 2 SE patients and 19 normal controls. 2. The number of EEC and the ratio of EEC/Epo-dependent CFU-E (EEC ratio) were positively correlated with the hemoglobin (Hb) levels (r = 0.608, P = 0.01) in PV patients, but did not correlate with white blood cell (WBC) counts, platelet counts and neutrophil alkaline phosphatase scores. 3. EEC did not correlate with PV patients' serum Epo levels (r = 0.518, P = 0.125). 4. Fifteen PV patients were treated with hydroxyurea and/or interferon-alpha. Their EEC ratio before treatment was correlated positively with the time required for complete remission (CR) (r = 0.651, P = 0.009) and negatively with the time before relapsing (r = -0.529, P < 0.02). 5. EECs of 7 PV patients treated with HU/IFN were decreased after their blood cell counts normalization. 6. There was a positive correlation between the EEC ratio and the attacks of vascular thrombosis (r = 0.524, P = 0.01). (7) The apoptosis of bone marrow mononuclear cells of PV patients was less than that of normal controls. PV patients' EEC was negatively correlated with the apoptosis of their bone marrow mononuclear cells (r = -0.192, P < 0.045).

CONCLUSIONEEC is peculiarly present in PV patients, and is a sensitive parameter in reflecting the abnormal hematopoietic clone burden and in diagnosing and monitoring the disease.

Adult ; Aged ; Apoptosis ; Bone Marrow Cells ; physiology ; Erythroid Precursor Cells ; physiology ; Erythropoietin ; blood ; Female ; Humans ; Male ; Middle Aged ; Polycythemia Vera ; blood ; therapy

OBJECTIVETo study the characteristics of cell cycle and proliferation of CD34+ hematopoietic stem cells in patients with myelodysplastic syndromes (MDS).

METHODSPropidium iodide staining was used to examine cell cycle parameters (G(0)/G(1), S and G(2)/M) of bone marrow mononuclear cells (BMMNCs) while immunofluorescent double staining and FACS techniques were used to measure Ki67 expression in BM CD34+ cells from normal control, patients with MDS, acute myeloid leukemia preceded by MDS (MDS-AML) and primary AML.

RESULTSThere was a statistical up-tendency in G(0)/G(1) phase proportion of BMMNCs whereas a statistical down-tendency in S and G(2)/M phase proportions among normal control, MDS and primary AML. Compared to primary AML, MDS-AML had significantly higher ratios of S (P < 0.05), G(2)/M (P < 0.05) and S + G(2)/M (P < 0.05) phase cells while lower ratio of G(0)/G(1) phase cells (P < 0.05). The proportion of CD34+Ki67+ cells in MDS patients was significantly higher than that in normal control (P = 0.004). So were the percentages of CD34+Ki67+ cells in low-risk [(0.54 +/- 0.49)%, P < 0.05] and high-risk MDS patients [(1.69 +/- 1.66)%, P = 0.022]. Furthermore, there was statistical difference between low-risk and high-risk MDS (P < 0.05). Compared to normal control and primary AML, MDS-patients had the highest proportion of CD34+Ki67+ cells [(16.75 +/- 13.58)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS patients [(48.50 +/- 20.49)%] was significantly higher than that in normal control [(27.71 +/- 16.04)%, P < 0.01]. So were the low-risk [(51.85 +/- 21.80)%, P = 0.002] and high-risk MDS [(43.93 +/- 18.57)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS-AML patients [(60.92 +/- 30.12)%] was the highest, and was statistically higher than that in both normal control (P < 0.01) and primary AML patients [(17.01 +/- 15.93)%, P < 0.001]. The proportion of CD34+Ki67+ cells in Ki67+ cells in MDS patients [(4.91 +/- 4.68)%, P < 0.01] was significantly higher than that [(2.43 +/- 2.37)%] in normal controls. In the low-risk MDS group it was (4.11 +/- 3.94)%, (P > 0.05) and in high-risk MDS group it was (5.76 +/- 5.38)%, (P < 0.05).

CONCLUSIONHigh proportion of G(0)/G(1) cells and G(1) phase arrest occurred in MDS. High proliferation capacity of MDS clone, especially that derived from CD34+ cells, might play an important role in the clonal expansion, diseases deterioration and worse prognosis of MDS.

Acute Disease ; Adolescent ; Adult ; Aged ; Antigens, CD34 ; blood ; Bone Marrow Cells ; metabolism ; pathology ; Cell Cycle ; Cell Proliferation ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Ki-67 Antigen ; blood ; Leukemia, Myeloid ; blood ; Male ; Middle Aged ; Myelodysplastic Syndromes ; blood ; Young Adult

OBJECTIVETo evaluate the patients with bone injury in Wenchuan earthquake.

METHODSFrom May 12th to June 15th 2008 the data of 1410 patients with bone injury in Wenchuan earthquake were analyzed to evaluate clinical intervention and remedy-managing experience.

RESULTSThe 1410 patients average age was from 4 to 103 years old. And 744 cases (52.7%) suffered from blunt injuries, 379 cases (26.9%) from buried injuries, 287 cases (20.4%) from falling injuries; And 1317 cases were with fracture, 93 with limbs soft tissue injuries; 261 patients combined with other parts of injuries including 45 cases with paralysis; 66 cases were with crush syndrome, 25 with gas gangrene, 76 with acute kidney failure, 26 with multiple organ failure. And 912 operations were performed including 402 fracture fixation, 224 debridement, 152 debridement and suture, 85 amputation, 29 implant skin, 8 fixation of joint dislocation, 5 surgical flaps transplantation, 4 nerve and tendon suture, 2 arthroscopes, 1 joint replacement. Among the 66 crush syndrome patients, 49 accepted continuous renal replacement therapy, in which 9 cases were bleeding from named arteries and 20 blood vessels were getting embolism. Among the 1410 cases, 1 died from multiple organ failure.

CONCLUSIONSAmong the patients with bone injury in Wenchuan earthquake, the elderly patients are more than the youth; The injuries are always combined with other complications; Opened injuries are polluted severely; It is difficult to deal with the crush syndrome; Paraplegia cases are less, but the amputees are more.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Earthquakes ; Female ; First Aid ; Humans ; Male ; Retrospective Studies ; Wounds and Injuries ; surgery

BACKGROUNDMyelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).

METHODSLeukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.

RESULTSDuring the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1 - 23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83 +/- 24.50)%], CD13 [(36.38 +/- 33.84)%], monocytic antigen CD14 [(38.50 +/- 24.60)%], and stem cell marker CD34 [(34.67 +/- 30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1 - 28) months, were found in patients with MDS-AML treated by induction chemotherapy.

CONCLUSIONSMDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.

Adolescent ; Adult ; Aged ; Chromosome Aberrations ; Female ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute ; etiology ; genetics ; immunology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; complications ; genetics ; immunology ; Prognosis