Spectrum-effect Model of Salvia miltiorrhiza Stem and Leaves Based on Enzymatic Activity / 中国实验方剂学杂志

Objective: Totally 12 batches of Salvia miltiorrhiza stem and leaves were taken as the research object,in order to investigate the correlation between the chromatographic peaks and the blood circulation activity in the HPLC fingerprint,and establish and verify the activity spectrum-effect model based on enzyme activity. Method: HPLC method and fibrinogen plate method were used to determine the fingerprint and in vitro activity values of stems and leaves of S. miltiorrhiza in 6 batches. SPSS was used to establish its spectrum-effect model by the principal component analysis-correlation analysis-multiple linear regression analysis method,and six batches of S. miltiorrhiza stems and leaves were used to verify the model. Result: Totally 7 characteristic peaks were obtained in the fingerprints of S. miltiorrhiza leaves. Kendalls tau-b correlation analysis showed the correlations between the blood circulating activity of S. miltiorrhiza stems and leaves and the 7 characteristic peak areas. The steep slope map analysis showed five optimal principal components of the model, namely protocatechualdehyde,caffeic acid,common peak 5 (to be identified), rosmarinic acid and salvianolic acid B. Among them,protocatechualdehyde,common peak 5 and salvianolic acid B showed a positive correlation with the activity of blood circulation,while caffeic acid and rosmarinic acid showed a negative correlation with the activity of blood circulation,with low mean relative errors between the predicted value and the measured value. Conclusion: The blood circulation activity spectrum-effect model based on enzyme activity can predict the blood circulation activity of stems and leaves of S. miltiorrhiza.

Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse.</p><p><b>METHODS</b>The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens.</p><p><b>RESULTS</b>After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05).</p><p><b>CONCLUSION</b>Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.</p>

Preliminary Clinical Efficiency of Autologous Peripheral Blood Mononuclear Cells for Treating Critical Limb Ischemia of Thromboangiitis Obliterans / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the long-term clinical effect of autologous peripheral blood mononuclear cells (PB-MNC) on critical limb ischemia (CLI) in patients with thromboangiitis obliterans (TAO) patients.</p><p><b>METHODS</b>The clinical data of 22 patients with CLI caused by TAO from July 2004 to May 2013 were analyzed retrospectively, 22 patients were divided into 2 groups; out of them 12 cases in one group were treated with granulocyte colony-stimulating factor (G-CSF)-mobilized autologous peripheral blood mononuclear cells (auto-PBMNC group), 10 cases in another group received conservative treatment (CT group). The log-rank test was used to compare the long-term outcomes in auto-PBMNC group and CT group.</p><p><b>RESULTS</b>The wound healing rate (P=0.016) and CLI-free rate (P=0.013) were significantly higher in PB-MNC group compared with that in CT group. No difference was found in amputation rates between the 2 groups (major amputation: P=0.361, minor and major amputation: P=0.867). No patients died or no serious adverse events occurred during the follow-up period.</p><p><b>CONCLUSION</b>The auto-PBMNC therapy can significantly promote the wound healing, and protect against CLI in TAO patients, but the risk of amputation is not low in comparison with conservative treatment.</p>

Organ toxicity and efficacy of high-dose daunorubicin-based chemotherapy in the treatment of acute leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and therapeutic effect of high-dose daunorubicin-based (HD-DNR) chemotherapy in the treatment of acute leukemia (AL).</p><p><b>METHODS</b>The clinical data of 25 AL patients, including 14 cases for induction chemotherapy, 8 for consolidation chemotherapy and 3 for reinduction therapy, which were treated with HD- DNR (DNR dosage of 90 mg/m(2)× 3 d) between June 2010 and August 2012 in our hospital were retrospectively analyzed, the adverse reaction of chemotherapy, especially cardiac toxicity and therapeutic effect were evaluated.</p><p><b>RESULTS</b>Most of the adverse reactions were mild, including cardiac toxicity, and no patient discontinued therapy because of HD-DNR related toxicities. Grade 3 or higher adverse reactions occurred only in the infection (56%) and diarrhea (12%). Withdrawal or dose reduction due to strong adverse reactions was not observed in all patients. Adverse reactions of infections (92%), lower ejection fraction(52.6%), diarrhea (48%), nausea (36%), vomiting (36%), dental ulcer (36%) and myocardial ischemia (32%) were relatively more common. The median time of neutrophil count reached to ≥ 0.5 × 10(9)/L and platelet ≥ 20 × 10(9)/L were both 21 days(ranged 9-31 and 9-38 days). Nine patients were complicated with infections before chemotherapy and 14 after chemotherapy, mainly occurred in gastrointestinal tract and respiratory system. Gastrointestinal, liver and kidney toxicity was slight. The cardiac ejection decreased in 10 cases, but only 1 reached grade 2 without clinical symptoms. Of the 14 AL patients for induction chemotherapy, 13 achieved hematological complete remission. Eight patients received HD-DNR as consolidation chemotherapy remained complete remission, while 3 refractory/relapsed patients remained non-remission.</p><p><b>CONCLUSION</b>The adverse reaction of HD-DNR based chemotherapy for AL treatment was mild, no obvious cardiac adverse reaction occurred. The treatment dose of DNR at 90 mg/m(2) × 3 d can be safely and effectively used to treat acute leukemia.</p>

Role of microenvironment in the process of expansion of late endothelial progenitor cell in vitro / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the role of the feeder layer cells as niche in the process of expansion of late endothelial progenitor cell in vitro.</p><p><b>METHODS</b>We cultured mononuclear cells (MNC)from human peripheral blood (PB)on the plate with the feeder layer cells which were irradiated late endothelial progenitor cells(EPC)or human umbilical vein endothelial cells (HUVEC) by EGM-2. After 21 days, the numbers of obtained late EPC colonies were counted separately, and their surface antigen of the late EPC was verified by fluorescence-activated cell sorter (FACS) analysis, and their ability of forming vessel structure with Matrigel in vitro. The differentiation of single stem cell on the feeder layer cell was traced by video-microscopy.</p><p><b>RESULTS</b>After 21 days of culture,(40.0±3.9)and(39.3±3.1)late EPC colonies that MNC of a hundred milliliter PB were cultured, respectively, on the feeder layer cells of EPC and HUVEC were much more than (2.0±1.3) colonies cultured on without the feeder layer cells (all P <0.05). These cells also expressed CD31,CD34,eNOS,FLt-1,P1H12,Sendo,VE cadherin,and CD117, as shown by FACS analysis. Furthermore, they formed vessel structure with Matrigel in vitro. The video-microscopy showed the asymmetric cell division was participated by the feeder layer cell during the expansion of single stem cell.</p><p><b>CONCLUSION</b>The massive expansion of late EPC can be achieved by the provision of the feeder layer cells, which may be involved in the stem cell asymmetric cell division.</p>

Analysis the advantage of autologous mobilized peripheral blood mononuclear cells transplantation on lower limbs ischemia disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the efficacy and its correlation with species of transplant cells of autologous mobilized peripheral blood (PB) mononucleated cells (MNCs) transplantation on 59 patients with lower limbs ischemia.</p><p><b>METHODS</b>Fifty-nine patients were evaluated with symptoms scores and after that their PBMNCs were mobilized and collected and then injected into the ischemic area at equal distance. They effectiveness and scores were evaluated at 7th day and 4th month after therapy. The correlation of CD34(+) cells and of MNCs with effectiveness was analysed respectively, and formula for correlations between them and effectiveness was calculated.</p><p><b>RESULTS</b>After MNCs injection, the effectiveness was observed both at 7th day and 4th month. The correlation of MNCs with effectiveness was stronger than that of CD34(+) cells (the effectiveness was represented by nimodipine value), According to the formula of nimodipine value, the value of the latter = 0.484 + 1.055 × CD34(+) cells number and the former = 0.288 + 0.401 × MNCs number with a correlation coefficient of R = 0.461 (P = 0.047) and R = 0.473 (P = 0.000) respectively.</p><p><b>CONCLUSION</b>Autologous mobilized PBMNCs number is a better indicator for effectiveness than CD34(+) cells number.</p>

Clinicopathologic study of splenic marginal zone B-cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of splenic marginal zone B-cell lymphoma (SMZL).</p><p><b>METHODS</b>The clinical data, histologic findings and immunophenotype of 8 SMZL cases were studied. IgH gene rearrangement was performed in 1 case. Follow-up information was available in 4 patients.</p><p><b>RESULTS</b>The median age of the patients was 61.5 years (range: 36 to 75 years). The male-to-female ratio was 1.7:1. All cases presented with massive splenomegaly. Five of six cases had abnormal blood counts: neutropenia and thrombocytopenia with two of them showing anemia. After splenectomy, the blood counts in 3/3 cases returned to normal levels. Post-operative fludarabine-based chemotherapy was given to 3 patients, two of them achieved complete remission and 1 case died during the course of chemotherapy. The average survival time was 21.5 months (range: 6 to 60 months). Histologically, all of the 8 cases showed micronodular white pulp lesions. Six of them exhibited the classic biphasic appearance with central aggregates of small B cells rimmed by a peripheral zone of atypical monocytoid B cells. The remaining 2 cases had a monomorphous appearance, consisting mainly of atypical monocytoid B cells. There was infiltration of tumor cells in the red pulp, sheets in appearance in all 8 cases. Immuno-histochemical staining showed CD20-positive (8/8), IgD-positive in 2 of the 4 cases (2/4), CD5-positive in 1 of the 4 cases (1/4), 6 of the 6 cases were bcl-2-positive, cyclin D1-negative and bcl-6/CD10-negative, CD43-negative in 5 of the 6 cases (5/6). The proliferation index, as highlighted by Ki-67 immunostaining, was low (< 15%).</p><p><b>CONCLUSIONS</b>SMZL is an indolent B-cell non-Hodgkin lymphoma. The main clinical manifestations are splenomegaly and abnormalities in blood counts. The main modality of treatment is splenectomy. Adjuvant fludarabine-based chemotherapy helps to achieve complete remission. In general, the prognosis of this lymphoma type is good. The lymphoma cells predominantly grow in micronodular pattern, with atypical monocytoid B cells rimming around the small B cells, which aggregates in the center. The differential diagnosis includes other small B-cell lymphomas and lymphoid hyperplasia of spleen.</p>

Occurrence of structural birth defect in high-prevalent areas of China / 中华流行病学杂志

<p><b>OBJECTIVE</b>This research was to compare the occurrence levels of birth defect, to describe the distribution of primary birth defects in different range of monitored ages and to provide data to China birth-defect monitoring system.</p><p><b>METHODS</b>A retrospective study on birth defect was conducted in two counties, Shanxi province, China, which covered birth defects among fetuses after 20 weeks' gestational age from 2002 through 2004. Data collected on birth defect cases mainly included extrinsic and visceral anomaly.</p><p><b>RESULTS</b>The occurrence rates of the monitored structural birth defects significantly increased with the increase of age. The occurrence rates were 17.6, 34.0, 43.6, and 53.7 per 1000 births, for different statistical range, from 20-week to 27-week gestational age, 7 days, 1 year and 3 years after birth, respectively. The range from 28-week gestational age to 7 days after birth was usually regarded as the routinely monitored range. If the occurrence rate was calculated from the 20-week gestational age, it appeared a 2.1-time increase. However, if the range was changed to 1 or 3 years after birth, the occurrence rate increased to 2.7 or 3.3 times high, respectively. The distribution of time when birth-defect was identified was significantly different by categories with majority of neural tube defect cases diagnosed at antepartum or 7 days after birth. Visceral defects were mainly found at 7 days after birth but increased with age, even some were diagnosed at 1 year after birth.</p><p><b>CONCLUSION</b>The routine Chinese monitoring program might detect approximately 1/3 of those structural birth defects with the base of current technique and monitoring range from 28-week gestational age to 7 days after birth. The result of our findings should be of help to other related studies.</p>

Efficacy of hepatitis B immunoglobulin in relation to the gene polymorphisms of human leukocyte Fcgamma receptor III (CD16) in Chinese liver transplant patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although the use of hepatitis B immunoglobulin (HBIG) may lead to a significant reduction in recurrent hepatitis B virus (HBV) infection and improve the survival of patients who have undergone liver transplantation (LT) for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients.</p><p><b>METHODS</b>Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing (ABI 3037). Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred.</p><p><b>RESULTS</b>Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 (45.5%) subjects, whereas TG in 31 (40.3%) and GG in 11 (14.3%). In the 559G carrier group (n = 42, 54.5%), the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group (n = 35, 45.5%), the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups (P < 0.05).</p><p><b>CONCLUSIONS</b>A single nucleotide polymorphism (T/G) at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detecting FCGR3A genotypes can be a clinical reference of the HBIG administration.</p>

Therapeutic neovascularization with autologous bone marrow CD34+ cells transplantation in hindlimb ischemia / 中华外科杂志

<p><b>OBJECTIVE</b>To explore whether transplantation of autologous bone marrow stem cells might augment angiogenesis and collateral vessel formation in a canine model of hindlimb ischemia.</p><p><b>METHODS</b>CD34(+) stem cells were centrifugation through Ficoll and an immune magnetic cell sorting system from bone marrow (20 ml) of canine (n = 5) and induced into endothelial cells with VEGF in vitro, and expression of von Willebrand factor. Bilateral hindlimb ischemia was surgically induced in canines and Dil fluorescence labeled autologous stem cells were transplanted into the ischemic tissues.</p><p><b>RESULTS</b>Four weeks after transplantation, fluorescence microscopy revealed that transplanted cells were incorporated into the capillary network among preserved skeletal myocytes. The stem cells transplanted group had more angiographically detectable collateral vessels, a higher capillary density (12.0 +/- 2.8 vs. 5.0 +/- 1.6 per field; t = 4.17 P < 0.05) and a higher ABI (0.58 +/- 0.14 vs. 0.32 +/- 0.11; t = 2.95, P < 0.05).</p><p><b>CONCLUSIONS</b>Direct local transplantation of autologous bone marrow CD34(+) stem cells seems to be a useful strategy for therapeutic neovascularization in ischemic tissues in adults, consistent with "therapeutic vasculogenesis."</p>

Impact of multidrug resistance 1 gene polymorphism on tacrolimus dose and concentration-to-dose ratio in Chinese liver transplantation recipients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether the polymorphism of multidrug resistance 1 gene (MDR1) in the donors and liver transplantation recipients was correlated with interindividual variation in tacrolimus dose requirement and concentration-to-dose ratio.</p><p><b>METHODS</b>The occurrence of MDR1 3435(C-->T) polymorphism was investigated by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 50 liver transplant recipients and their corresponding donors. Doses (mg/kg body weight) and dose-adjusted trough levels (ng/mL per mg/kg body weight) were compared according to allelic status for MDR1.</p><p><b>RESULTS</b>The MDR1 genotype CC was observed in 23 subjects (23%), whereas 64 (64%) were CT and 13 (13%) were TT. Tacrolimus doses required to achieve target blood concentrations were higher in the patients with MDR1 CC genotype than in the CT or TT genotype patients, and the dose-adjusted trough levels were lower. No significant differences were found in tacrolimus doses or dose-adjusted trough levels according to the donor's MDR1 genotype.</p><p><b>CONCLUSION</b>Tacrolimus dose requirement and dose-adjusted trough levels were correlated with MDR1 3435 (C-->T) polymorphism, and MDR1 3435 (C-->T) polymorphism analysis is helpful to individualize tacrolimus administration.</p>

The establishment of the two dimensional gel electrophoresis (2-DE) map of hypertrophic scar epidermal cells and the display of the differentially expressed proteins / 中华整形外科杂志

<p><b>OBJECTIVE</b>To establish and optimize the two dimensional gel electrophoresis (2-DE) map of epidermal cells separated from the hypertrophic scar tissues so as to explore the function of the non cultured epidermal cells during the course of the formation of hypertrophic scar.</p><p><b>METHODS</b>To separate the epidermal cells from the scar tissues, the scar epidermis was digested with Dispase II and trypsin. The total protein of the cells was then extracted and separated with 2-DE and visualized with silver stain. Spots detection and matching were performed with Melaine 3.0 gels analyzing software. The results were then compared with the normal epidermal cells' 2-DE map coming from the Danish Center for Human Genome Research' s 2-DE PAGE Databases.</p><p><b>RESULTS</b>Nearly more than 600 protein spots were identified in the final optimized 2-DE map. We found out 24 differentially expressed proteins by comparing the difference in composition, shape or density of all the spots. In the 24 proteins, there are 8 up-regulated ones, 9 down-regulated ones, 4 disappeared ones and 3 newly founded ones.</p><p><b>CONCLUSIONS</b>The method of digesting the epidermis with Dispase II and trypsin to separate the epidermal cells to establish the 2-DE map is feasible and it made the further study on hypertrophic scar proteomics possible. The 24 differentially expressed proteins revealed that epidermal cells might play a role in the formation of hypertrophic scar.</p>

Inhibition of tumor angiogenesis in nude mice by adenovirus-mediated PF4 p17-70 cDNA transfection / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the in vivo effect of modified platelet factor 4 (PF4)-p17-70 cDNA on tumor angiogenesis in nude mice.</p><p><b>METHODS</b>The p17-70 cDNA was cloned into the AdEasy system to transfect packing cell line 293 and produce viral particles encoding p17-70cDNA (Ad p17-70). The integration of p17-70 cDNA was confirmed by RT-PCR and the P17-40 peptide Western blot. The biological activity of purified recombinant adenovirus was determined by umbilical veinal endothelial cell proliferation assay in vitro and in vivo tumor angiogenesis suppression of nude mice bearing human head and neck carcinoma.</p><p><b>RESULTS</b>p17-70 significantly inhibited in vitro proliferation of endothelial cells being 58% lower than that of empty vector and reduced tumor volume in vivo. The tumor mass was (0.086 +/- 0.054) g, (0.171 +/- 0.076) g and (0.195 +/- 0.067) g, the tumor volume was (16.7 +/- 5.2) mm(3), (36.5 +/- 23.7) mm(3) and (41.5 +/- 12.2) mm(3) in p17-70 cDNA transfected group, empty vector group and PBS group, respectively. Immunohistochemical staining demonstrated a decreased number of blood vessels in the tumors.</p><p><b>CONCLUSION</b>P17-70 peptide mediated by adenoviral vector could inhibit the endothelial proliferation in vitro and the tumor growth in vivo.</p>