Nano-components derived from Descurainiae Semen Carbonisatum and its hemostatic mechanism / 药学学报

A novel sort of nano-component was extricated and isolated from Descurainiae Semen Carbonisatum (DSC), and its hemostatic component was considered through pharmacological experiments. A muffle furnace was used to prepare DSC at 250 ℃, 300 ℃ and 350 ℃, and the DSC dialysate at each temperature was obtained by the extraction and separation method. Low-resolution transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM) were utilized to characterize the nano-components. Ultraviolet spectroscopy (UV-Vis), fluorescence spectroscopy (FL) and infrared spectroscopy (FTIR) were utilized to measure its optical characteristics and functional group information. The anti-hemorrhagic effects were evaluated by liver bleeding tests and the related hemostatic mechanisms of the obtained nano-components were further assessed by detecting blood coagulation and PLT quantity to discuss the hemostasis mechanism. The experiments complied with the Animal Ethics Committee of Beijing University of Chinese Medicine. TEM results showed that there was a novel type of nano-component in the DSC dialysate bag, which was named DSC nano-components (DSC-NCs). The experimental results of liver bleeding in mice showed that DSC-NCs prepared at 250 ℃, 300 ℃, and 350 ℃ could reduce the bleeding time of mice liver. Among them, DSC-NCs prepared at 350 °C had the best effect. In addition, DSC-NCs prepared at various temperatures can also reduce the prothrombin time (PT) value, increase the fibrinogen (FIB) value and the platelet (PLT) value to varying degrees. DSC-NCs have a certain hemostatic effect, which may be related to the activation of the exogenous coagulation system, the increase of FIB value and the increase of platelet content. This provides a new research direction for exploring the treatment of bleeding diseases, and provides a new perspective for the potential application of DSC-NCs in the medical field.

Effect of 15-Deoxy-△(12,14)-prostaglandin J2 on Expression of Macrophage Migration Inhibitory Factor in Mouse Monocyte/macrophage Cell Line J774A.1 / 中国医学科学院学报

Objective To investigate the effect of 15-Deoxy-△(12,14)-prostaglandin J2 (15 d-PGJ2) on the expression of macrophage migration inhibitory factor (MIF) and its underlying mechanism in J774A.1. Methods The murine monocyte/macrophage cell line J774A.1 were divided into six groups:lipopolysaccharide (LPS) group,incubated with 1 μg/ml LPS for 1 h;normal control group,incubated with PBS for 1 h;negative control group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h;15 d-PGJ2 group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h followed by 1 μg/ml LPS for 1 h;GW9662 group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h following GW9662 10 μmol/L for 1 h,and then incubated with 1 μg/ml LPS for 1 h;and Vehicle group,control of GW9662,GW9662 was replaced by its solvent DMSO. The expression of MIF was detected via immunofluorescence and agarose gel electrophoresis. RT-qPCR and Western blotting were used to test whether 15 d-PGJ2 could regulate mRNA and protein expression of MIF in J774A.1 upon LPS challenge. The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist GW9662 on the regulation of MIF by 15 d-PGJ2 was observed. The effects of 15 d-PGJ2 on the nuclear translocation of PPAR-γ upon LPS challenge were detected via high content screening analysis. Results MIF DNA and protein expressions were detected in J774A.1. MIF mRNA expression was up-regulated (1.75±0.09,P=0.037) when challenged with LPS and 15 d-PGJ2 inhibited its upregulation (0.84±0.08,P=0.026) in J774A.1. The protein level was consistent with the mRNA level. PPAR-γ antagonist GW9662 reversed the effect of 15 d-PGJ2 (mRNA,1.48±0.06,P=0.016;protein,1.28). Furthermore,nuclear translocation of PPAR-γ was regulated by 15 d-PGJ2 in J774A.1 upon LPS challenge(1.39±0.02 vs. 1.01±0.03,P=0.003). Conclusion 15 d-PGJ2 may down-regulate the MIF expression in J774A.1 in a PPAR-γ-dependent manner.

Busulfan Combined with Cyclophosphamide as the Conditioning Regimen in Patients with Multiple Myeloma Treated by Autolo-gous Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the safety and efficacy of busulfan (BU) combined with cyclophosphamide (CY) as the conditioning regimen of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM).</p><p><b>METHODS</b>The safety and efficacy of the BUCY regimen were evaluated through observing the adverse reactions, recovery of hematopoietic reconstitution, response and survival in 20 patients after auto-HSCT.</p><p><b>RESULTS</b>In 20 MM patients with median age 52.5 (38-66), the neutrophil and platelet counts recovered at 10(8-18) d and 10 (8-17) d after auto-HSCT respectively, the treatment related mortality during 100 days after auto-HSCT was 0, the partial remission (PR) rate decreased from 31.58% to 0 (P < 0.05) after auto-HSCT, only 1 patient was in progression of disease, all patients were alived.</p><p><b>CONCLUSION</b>For patients with MM treated with Auto-HSCT, the BUCY regimen is ideal in safety and response, but the long-term effect still should be observed.</p>

Clinical Analysis on Treatment of Chronic Myelomonocytic Leukemia with Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze retrospectively the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).</p><p><b>METHODS</b>The engraftment, graft versus host disease (GVHD), infection, relapse, and survival of 13 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.</p><p><b>RESULTS</b>Thirteen (10 males and 3 females) CMML patients with a median age of 38 years old received allo-HSCT including 4 from HLA-matched unrelated donors, 6 from HLA-matched sibling donors and 3 from haploidentical related donors. All 13 patients achieved engraftment, and the median time of neutrophil engraftment and platelet engraftment were 12 (11-18) days and 15 (10-55) days respectively, acute GVHD occurred in 8 patients. After the median follow-up of 13 (6-29) months, the overall survival, disease free survival and relapse were 53.8%, 53.8%, 7.7%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT can improve the survival of patients with CMML, and is a effective method for treatment of CMML.</p>

Efficacy and safety study of subcutaneous injection of bortezomib in the treatment of de novo patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of subcutaneous injection of bortezomib in the treatment of de novo multiple myeloma (MM) patients.</p><p><b>METHODS</b>A total of 36 MM patients treated with bortezomib, adriamycin and dexamethasone (PAD) from January 2012 to April 2013 were analyzed. Among them, 18 received improved PAD (improved PAD group) with the subcutaneous injection of bortezomib, another 18 received conventional PAD (PAD group). The efficacy and safety of two groups were analyzed.</p><p><b>RESULTS</b>Except 4 cases can not be assessed, 32 patients were evaluated. Of 32 cases, 19(59.4%) achieved complete remission (CR) or very good partial remission (VGPR) after induction therapy, which were 61.1% and 57.1% for PAD group and improved PAD group, respectively (P=1.000). No significant difference between the time to achieve maximum effectiveness in two groups was detected. In the PAD group, one patient (5.6%) died of serious lung infection and eight (44.4%) experienced grade 3 or higher adverse events, while only one (5.6%) discontinued treatment in improved PAD group due to similar toxicity. Compared to PAD group, grade 3 or worse adverse events was significantly reduced in improved PAD group, the most common symptoms were leucopenia (33.3% vs 61.1%, P=0.086), thrombocytopenia (50.0% vs 61.1%), anaemia (27.8% vs 16.7%), infection (16.7% vs 50.0%, P=0.075), diarrhea (5.6% vs 33.3%, P=0.088), peripheral neuropathy(0 vs 27.8%, P=0.045).</p><p><b>CONCLUSION</b>The improved PAD regimen by changing bortezomib from intravenous administration to subcutaneous injection significantly reduced adverse events, improved the safety of clinical application of bortezomib without affecting curative effect, and had great progress.</p>

Analysis of correlation between serum thymidine kinase 1 and acute myeloid leukemia / 中国实验血液学杂志

This study was purposed to investigate the clinical significance of serum thymidine kinase 1 (STK1) level change in acute myeloid leukemia (AML). Peripheral blood samples of 60 newly diagnosed AML patients were collected and the STK1 levels were determined by enhanced chemiluminescent dot-blot method before and at two weeks after start of inductive treatment and in consolidatory treatment. Using non-parametric test, the differences between groups were analyzed. Then the correlation between STK1 level and clinical characteristics was explored by a way of chi-square test. The results indicated that the serum TK1 level in complete remission (CR) or partial remission (PR) AML patients decreased in varying degree as compared to pretreatment (P < 0.05), while there was no significant difference of TK1 level in non-remission (NR) ones (P > 0.05). The serum TK1 level in CR patients remained low level but increased noticeably after relapse into progressive disease (P < 0.05). A significant correlation was found between STK1 level and chromosomal abnormalities, serum LDH level as well as whether had fever in de novo AML patients (P < 0.05). It is concluded that the serum TK1 level change may be applied for reflecting the aggressiveness of disease, monitoring the clinical response to chemotherapy, evaluating the prognosis and predicating the relapse risk. The decrease of TK1 level suggests effective treatment and tumor burden reduction, while its increase indicate poor prognosis and relapse risk.

Repair of cervical scar contracture with flaps containing cervical cutaneous branch of the transverse cervical artery / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of repairing cervical scar contracture using flaps carrying cervical cutaneous branch of the transverse cervical artery.</p><p><b>METHODS</b>Sixty-six patients with scar contracture after burn in anterior region of neck hospitalized from 1988 to 2011. The scars were excised and repaired with flaps containing the cervical cutaneous branch of transverse cervical artery. They included 55 island flaps (with 9 flaps pre-expanded) and 11 non-island flaps (with 1 flap pre-expanded). After removing the scar and releasing the contracture, flaps with the cervical cutaneous branch of transverse cervical artery were designed and raised in the supraclavicular and infraclavicular regions and the anterior thoracic region. The axial vessel of the flap was the cutaneous artery, which perforated in the crossing area of sternocleidomastoid muscle and omohyoid muscle and originated from the transverse cervical artery. The posterior borderline of the flap reached the anterior border of the trapezius muscle. Its exterior borderline reached the middle part of deltoid muscle, and its interior borderline ended at the midsternal line. The lower borderline was located 3.0-4.0 cm below the nipple. The incisions at the interior, lower, and exterior borders of the flap were first made. Then after sharp dissection to the clavicle, blunt dissection was performed to the pedicle to allow the flaps to be able to cover the wound after rotation without undue tension. The pre-expanded donor sites were sutured directly, while the un-expanded ones were covered with skin graft.</p><p><b>RESULTS</b>Out of the 66 flaps, 64 flaps survived. Two flaps showed partial necrosis at the distal end due to sub-flap hematoma, and they healed after skin grafting. All the donor sites healed. The color and texture of all flaps matched well with the surrounding skin tissue. The flaps regained sensation pertaining to the chest in the early stage, and complete sensation pertaining to the neck appeared 6 months after surgery.</p><p><b>CONCLUSIONS</b>The flap containing cervical cutaneous branch of the transverse cervical artery is a good choice for repairing severe cervical scar contracture for its simple harvest, reliable blood supply, and similar color and texture to the skin of cervical region.</p>

Analysis of tyrosine kinases gene mutations in core binding factor related acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the prevalence of several tyrosine kinases (TKs) gene mutations including c-Kit, FLT3 and JAK2 V617F in core binding factor related acute myeloid leukemia (CBF-AML), and analyze their impact on clinical characteristics and prognosis.</p><p><b>METHODS</b>Mutations of c-Kit, FLT3-ITD and FLT3-TKD were detected by genomic DNA PCR and sequencing, and JAK2 V617F mutation screening by allele-specific PCR in 58 newly diagnosed CBF-AML patients [28 AML with inv(16) and 30 with t(8;21)], and analyze the patients clinical characteristics and prognoses.</p><p><b>RESULTS</b>c-Kit aberrations were detected in 32.8% cases, including 6 cases mutated in exon 8 (mutKIT8) and 13 mutated in exon 17 (mutKIT17). MutKIT8 was more prominent in inv(16) than in t(8;21) patients (21.4% vs 0, P = 0.009). Only 2 cases had FLT3-ITD and 7 (12.1%) FLT3-TKD mutations. The result of JAK2 V617F mutation screenings in these CBF-AML patients was negative. The frequency of receptor tyrosine kinases(RTK) mutations was 46.6% and only one case had two kinds of missense mutations (mutKIT8 & TKD(+)). Median age of onset was higher for mutKIT17 than for wide-type c-Kit (wtKIT) patients (55 vs 31, P = 0.003). c-Kit mutations were significantly associated with decreased overall survival (OS) and continuous complete remission (CCR) rates (P = 0.053, and 0.048 respectively), and so did more for exon17 mutated patients reduced (P = 0.005, and 0.013 respectively). FLT3-TKD mutation showed no effects on prognosis of CBF-AML patients.</p><p><b>CONCLUSIONS</b>RTK mutations are common in patients with CBF-AML. c-Kit mutations frequently and JAK2V617F mutation rarely appear in CBF-AML. c-Kit mutations, especially mutKIT17 confers higher relapse risk and poorer prognosis.</p>

Detection of JAK2V617F mutation and its clinical significance in 80 patients with M2 acute myelogenous leukemia / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the prevalence and prognostic significance of JAK2V617F gene mutation in acute myelogenous leukemia M2 (AML-M2) patients.</p><p><b>METHODS</b>Allele specific polymerase chain reaction (PCR) was used to detect JAK2 gene mutation.</p><p><b>RESULTS</b>Of 80 de novo AML-M2 patients, 6 at the time of first diagnosis and 1 at relapse were found to have JAK2V617F gene mutation (8.8%, 7/80). Morphologically, the whole blood and bone marrow of the 7 AML-M2 patients with JAK2V617F gene mutation presented a picture of acute leukemia instead of myeloproliferative disorders. Immunophenotypically, bone marrow samples showed myelogenous linage expression. Complete remission was obtained in 4 of 5 AML-M2 patients with JAK2V617F mutation who received treatment, while one patient had no response to the treatment. Follow-up was performed in all the 5 patients, with a median survival of 18.5 months in 4 patients.</p><p><b>CONCLUSION</b>JAK2V617F gene mutation, as a type-1 mutation, might not be an initial event in the pathogenesis of acute myelogenous leukemia, and its presentation does not mean a poor prognosis in de novo AML patients.</p>

Relationship between CMV reactivation and KIR haplotype/HLA-Cw genotype in patients after unrelated-donor hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between CMV reactivation and KIR haplotype or HLA-Cw genotype in patients after unrelated-donor hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>From January 2003 to December 2008 the HLA-Cw/KIR genotype of 48 patient-donor pairs were determined by polymerase chain reaction with sequence specific primers (PCR-SSP) and sequence specific nucleotide (PCR-SSOP). Posttransplant CMV reactivation was performed by immune histochemically assay.</p><p><b>RESULTS</b>Of 48 patients, 15 were transplanted from unrelated donors with an antigen mismatch for HLA Cw and 33 patient-donor pairs were matched for HLA-Cw. The CMV reaction rate was 66.7% for HLA-Cw mismatch group and 48.5% for HLA-Cw match group (chi(2) = 1.39, P = 0.2375). Thirty-seven donor-patients pairs belonged to group C1 and 11 to group C2, and CMV reaction rate was 64.9% in group C1 and 18.2% in group C2 (chi(2) = 18.13, P < 0.0001). Twenty-six patients received graft from KIR haplotype A (group A donor) and 22 from KIR haplotype B donors (group B donor) and CMV reaction rate was 57.7% in group A donor and 50.0% in group B donor (chi(2) = 0.28, P = 0.5941). The number of donor activating KIRs (aKIRs) was less than that of recipient aKIRs in 34 patient-donor pairs in which the CMV reaction rate was 70.6%, and the number of donor aKIRs was more than that of recipient aKIRs in 14 patient-donor pairs in which the CMV reactivation was 14.3%. There was a significan difference between the two group (chi(2) = 12.44, P = 0.0004).</p><p><b>CONCLUSION</b>KIR and HLA-Cw genotypes influence the rate of CMV reactivation following non-T cell deleted unrelated donor hematopoietic cell transplantation.</p>

Analysis of c-kit and JAK2 gene mutations in t(8;21) acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the prevalence of c-kit and JAK2 gene mutations in protein tyrosine kinase (PTK) family in adult t(8;21) acute myeloid leukemia (AML) and their implications.</p><p><b>METHODS</b>Genomic DNAs from 78 t(8;21) AML patients were screened for mutated c-kit (mutKIT) in exon 8 and 17 by PCR and sequencing. JAK2 V617F mutation screening was processed by allele-specific PCR.</p><p><b>RESULTS</b>(1) Among 78 t(8;21) AML patients, 27 (34.6%) had muc-kit/JAK2 and 6 (7.7%) had JAK2 V617F, and none had both. (2) Peripheral WBC count was higher in mutKIT/JAK2 V617F patients than in wide-type c-kit/JAK2 (wtKIT/JAK2) patients \[(36.2 +/- 37.7) x 10(9)/L vs (21.7 +/- 21.1) x 10(9)/L\] (P < 0.05). There was no significant difference in hemoglobin level, platelet counts, percentage of blast cell in bone marrow, CD117 expression level, the age of onset and gender between the two groups. Peripheral WBC count was higher in mutKIT patients \[(38.8 +/- 40.7) x 10(9)/L\] than in wtKIT patients \[(22.0 +/- 20.4) x 10(9)/L\] (P < 0.05). (3) Complete remission (CR) rates between patients with mutkit/JAK2 V617F and with wtKIT/JAK2 were similar (69.6% vs 80.0%, P > 0.05), but the 2 year continuous CR (CCR) rate was lower in patients with mutKIT/JAK2 V617F (26.7% vs 56.1%, P < 0.05). However, there was no significant difference in OS between mutKIT/JAK2 V617F and wtKIT/JAK2 patients (34.8% vs 58.6%, P > 0.05).</p><p><b>CONCLUSIONS</b>Occurrence of c-kit and JAK2 gene mutations especially c-kit mutation is common in t(8;21) AML patients, and is associated with higher WBC. These mutations confer higher relapse risk and predict poor prognosis.</p>