Relationship between HLA Gene Polymorphism and Aplastic Anemia in Northern Chinese Han Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between HLA-A, -B, -C, -DRB1, -DQB1 gene polymorphism and aplastic anemia （AA）of 65 cases in Northern China.@*METHODS@#The high resolution genotyping of HLA-A, -B, -C, -DRB1, -DQB1 alleles in 65 AA patients and 772 healthy controls was performed with polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO), the relationship between HLA-A, -B, -C, -DRB1, -DQB1 gene polymorphism and aplastic anemia was analyzed by Pearson Chi-square，Continuity Correction， Two-sided Fisher's Exact Test and Odds Ratio.@*RESULTS@#The HLA-B*1302（10% vs 4.21%）, B*3501（7.69% vs 3.89%）, DRB1* 0701（10% vs 4.73%）, DRB1*0901（19.23% vs 7.58%）, DQB1*0202（9.23% vs 3.76%） gene frequency in AA patients was higher than those in health controls, the difference was statistically significant (P<0.05), the χ were 9.049, 4.336, 6.838, 20.974 and 8.968, OR ratio was 2.528, 2.061, 2.239, 2.904 and 2.605. However, the HLA-A*3303（1.54% vs 6.93%）, DQB1*0302（1.54% vs 6.02%） gene frequency in AA patients was lower than those in healthy controls, the difference was statistically significant (P<0.05), the χ was 5.726 and 4.505, the OR ratio were 0.210 and 0.244.@*CONCLUSION@#The polymorphism of HLA-A, -B, -DRB1, -DQB1 alleles is associate with AA in these patient cases, the HLA-B*1302, HLA-B*3501, HLA-DRB1*0701, HLA-DRB1*0901 and HLA-DQB1*0202 may be sensitive genes to AA, while the HLA-A*3303 and HLA-DQB1*0302 may be protective genes on AA.

Effect of Serum on Cultured Astrocytes Morphology and Expression of Aquaporin-4 in Rats / 中国康复理论与实践

Objective To explore the effect of blood-brain barrier disruption on expression of AQP-4,through comparing the cell morphology and the expression of aquaporin-4(AQP-4)of cultured astrocytes in medium with and without fetal bovine serum(FBS). Methods Cerebral cortical astrocytes from female Wistar rats were cultured in serum free medium,DMEM supplement-ed with 10% FBS,and serum free medium supplemented with 10% FBS.Phase contrast microscope was used to detect the cell morphology and cell size. Immunofluorescence staining and reverse real-time quantitative poly-merase chain reaction(RT-qPCR)were used to examine the expression of glial fibrillary acidic protein(GFAP), AQP-4 and metabotropic glutamate receptor 5(mGluR5). Results Astrocytes in serum free medium showed extensive process bearing morphology,small body and nucleus,and high refractivity.In contrast,in two kinds of 10% FBS-containing medium,astrocytes were flat with large body and nucleus,weak refractivity,as well as short process.Analysis of immunofluorescence staining and RT-qPCR revealed a down-regulation of GFAP and AQP-4 protein and mRNA expression in two kinds of 10% FBS-con-taining medium, compared with that in serum free medium (P<0.001), however, there was no difference in mGluR5 protein and mRNA expression(P>0.05). Conclusion FBS changed astrocyte morphology and down-regulated the expression of GFAP and AQP-4.

Efficacy and Safety of Posaconazoleon for Primary Antifungal Prophylaxis against Invasive Fungal Disease in Patients with Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and clinical safety of posaconazoleon primary antifungal prophylaxis against invasive fungal disease (IFD) in patients with stem cell transplantation.</p><p><b>METHODS</b>At the start from preconditioning regimen, 45 patients without IFD were administered with posaconazoleon until neutrophils greater than 0.5×10/L, 35 patients treated with micafungin were enrolled in control group. The incidence, risk factors of IFD and side effects of medicines were evaluated.</p><p><b>RESULTS</b>Of the total 80 patients, 13(16%) had IFD within 100 days after allo-HSCT. The overall survival was significantly different between patients with or without IFD by Kaplan-Meier survival curve analysis (P<0.05). Out of the 45 cases in posaconazoleon group, IFD occurred in 4 cases (9%). In contrast, the incidence of IFD in control group was 26%(9 out of 35) (P<0.05). The risk factors of IFD and side effects were not significantly different between 2 groups(P>0.05).</p><p><b>CONCLUSION</b>The primary prevention efficancy of IFD by posaconazoleon after allo-HSCT is much better than that of micafungin with well tolerability and satisfactory efficacy.</p>

Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation Using Tumor-ablative Conditioning Regimen for Patients with Refractory/Relapsed Non-Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and effectiveness of autologous hematopoietic stem cell transplantation (auto-HSCT) using tumor-ablative conditioning regiment for patients with refractory/relapsed non-Hodgkin's lymphoma.</p><p><b>METHODS</b>The clinical data of 16 patients with refractory/relapsed non-Hodgkin's lymphoma received above-mentioned therapeutic regimen from January 2013 to July 2015 was analyzed retrospectively, and conditioning-related toxicity, engraftment, infection, relapse and survival rate were evaluated.</p><p><b>RESULTS</b>No conditioning-related organs' failure and mortality were found. Only 1 patient had not been engrafted, and the engraftment rate was 93.7%. The incidence of serious infection was 31.2%. The median follow-up was 20.5(1-30) months, and 3 patients died, out of them 2 patients died of relapse. Two year overall survival (OS) , disease-free survival (DFS) and relapse rates were 80.2%, 74.5% and 20.6% respectively.</p><p><b>CONCLUSION</b>Auto-HSCT using tumor-ablative conditioning regimen is safe and effective for patients with refractory/relapsed non-Hodgkin's lymphoma, and it possess a certain effect for reducing disease relapse after transplantation.</p>

Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning.</p><p><b>METHODS</b>The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells.</p><p><b>RESULTS</b>All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58).</p><p><b>CONCLUSION</b>After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.</p>

Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury.</p><p><b>METHODS</b>The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups.</p><p><b>RESULTS</b>Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury.</p><p><b>CONCLUSION</b>These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.</p>

Pathogenicity of Five Strains of Toxoplasma gondii from Different Animals to Chickens

Toxoplasma gondii is a protozoan parasite with a broad range of intermediate hosts. Chickens as important food-producing animals can also serve as intermediate hosts. To date, experimental studies on the pathogenicity of T. gondii in broiler chickens were rarely reported. The objective of the present study was to compare the pathogenicity of 5 different T. gondii strains (RH, CN, JS, CAT2, and CAT3) from various host species origin in 10-day-old chickens. Each group of chickens was infected intraperitoneally with 5 x 10(8), 1 x 10(8), 1 x 10(7), and 1 x 10(6) tachyzoites of the 5 strains, respectively. The negative control group was mockly inoculated with PBS alone. After infection, clinical symptoms and rectal temperatures of all the chickens were checked daily. Dead chickens during acute phage of the infection were checked for T. gondii tachyzoites by microscope, while living cases were checked for T. gondii infection at day 53 post-inoculation (PI) by PCR method. Histopathological sections were used to observe the pathological changes in the dead chickens and the living animals at day 53 PI. No significant differences were found in survival periods, histopathological findings, and clinical symptoms among the chickens infected with the RH, CN, CAT2, and CAT3 strains. Histopathological findings and clinical symptoms of the JS (chicken origin) group were similar to the others. However, average survival times of infected chickens of the JS group inoculated with 5 x 10(8) and 1 x 10(8) tachyzoites were 30.0 and 188.4 hr, respectively, significantly shorter than those of the other 4 mammalian isolates. Chickens exposed to 10(8) of T. gondii tachyzoites and higher showed acute signs of toxoplasmosis, and the lesions were relatively more severe than those exposed to lower doses. The results indicated that the pathogenicity of JS strain was comparatively stronger to the chicken, and the pathogenicity was dose-dependent.

Clinical Efficacy of Decitabine Combined with CAG Regimen for Myelodysplastic Syndrome-RAEB and Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy and side effects of treating patients with myelodysplastic syndrome-RAEB (MDS-RAEB) and with refractory acute myeloid leukemia (AML) by using decitabine combined with CAG regimen.</p><p><b>METHODS</b>Clinical data of 21 patients with MDS-RAEB or refractory AML from July 2011 to July 2014 were analyzed retrospectively. Among 21 patients there were 4 cases of MDS-RAEB and 17 cases of refractory AML; 12 cases were beyond 60 years old; 13 cases had high-risk karyotypes. All the patients received decitabine combined with CAG regimen consisting of decitabine 20 mg/(m(2) · d), d 1-5; aclarubicin 10 mg/d, d 6-13; cytarabine 20 mg/d, d 6-19; G-CSF 300 µg/d, d 6-19.</p><p><b>RESULTS</b>After 1 cycle of treatment with DCAG regimen, the outcome of 21 patients showed that 8 cases achieved complete remission (42.1%), 8 cases achieved partial remission (42.1%), 2 cases achieved hematologic improvement, 1 cases achieved non-remission and 2 cases died; and the 1 year overall survival rate was 67.5%. The outcome of 12 patients beyond 60 years old showed that 6 cases achieved complete renission (60%, 6/10), and the 1 year overall survival rate was 62.5%. The outcome of 13 patients with high-risk karytype showed that 6 cases achieved complete renission (54.5%, 6/11), and the 1 year overall survival rate was 61.5%. The main adverse event was myelosuppression, and non-hematological toxicity included liver dysfunction and gastrointestinal tract reaction.</p><p><b>CONCLUSION</b>Decitabine combined with CAG regimen is effective and safe for treatment of MDS-RAEB and refractory AML patients, which can prolong lives of patiens with refractory hematological diseases.</p>

Clinical observation of haploidentical-hematopoietic stem cell transplantation combined with human umbilical cord-derived mesenchymal stem cells for severe aplastic anemia-II / 中国实验血液学杂志

This study was purposed to investigate the efficacy and safety of haploidentical hematopoietic stem cells (allo-HSCT) transplantation combined with human umbilical cord-derived mesenchymal stem cell infusion (hUC-MSC) for severe aplastic anemia-II (SAA-II). Eight SAA-II patients received haploidentical allo-HSCT, the G-CSF mobilized peripheral hematopoietic stem cells and bone marrow haploidentical hematopoietic stem cells were selected as graft, the human umbilical cord-derived mesenchymal stem cells (hUC-MSC) were infused as the third party. Conditioning regimen consisted of rabbit anti-thymic lymphocytes protein(ATG), cyclophosphamide(CTX) and fludarabine(Flu). For two patients out of 8 SAA-II patients the conditioning regimen was combined with busulfan(BU). The graft versus host disease(GVHD) was prevented with CSA, MTX, ATG, CD25 and mycophenolate mofetil. The results showed that the average number of nucleated cells were 9.13×10(8)/kg, and number of CD34(+)cells were 3.76×10(6)/ kg. All the 8 SAA-II patients achieved hematopoietic reconstitution. The average time of neutrophils count>0.5×10(9)/L was 11.9 days, and average time of Plt level >20×10(9)/L was 14.6 days. The incidence of acute GVHD of I-II grade was 25%, and that of III-IVgrade was 12.5%, the transplantation-related mortality was 25%. It is concluded that haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA.

Transplantation of umbilical cord mesenchymal stem cells combined with haploidentical hematopoietic stem cells for 36 patients with refractory/relapsed myeloid leukemia / 中国实验血液学杂志

This study was purposed to analyse the clinical efficacy of transplantation of umbilical cord mesenchymal stem cells (UC-MSC) combined with haploidentical hematopoietic stem cells (haplo-HSCT) for patients with refractory/relapsed myeloid leukemia. The clinical data of 36 patients received transplantation of UC-MSC combined with haplo-HSCT from January 2007 to June 2013 were summarized retrospectively, the engraftment, GVHD and 2 years-overall survival (OS) were analysed. The results showed that the median times of neutrophil count>0.50×10(9)/L and platelet count>20×10(9)/L were 12.0 days and 14.0 days, respectively. Grade III to IV aGVHD occurred in 5 out of 36 patients (13.8%). cGVHD occurred in 12 out of 32 patients (37.5%) and extensive cGVHD occurred in 2 patients. Additionally, only 3 patients (8.3%) experienced relapse. The 2-year OS rate of patients was 76.9%. It is concluded that the transplantation of UC-MSC combined with haplo-HSCT has good therapeutic efficacy for patients with refractory/relapsed myeloid leukemia, and may be served as a therapeutic method especially for patients with high risk and without well matched donor.

Transplantation of haploidentical-hematopoietic stem cells combined with two kind of third part cells for chronic aplastic anemia: one case report / 中国实验血液学杂志

This study was purposed to investigate the safety and effectivity of haploidentical stem cell transplantation for chronic aplastic anemia (CAA) by using two kind of third part cells: umbilical cord derived mesenchymal stem cells (hUC-MSC) and haploidentical umbilical cord blood cells. The patient is a girl of 12 year old with CAA for 11 years. The donor was her mother. Graft come from haploidentical hematopoietic bone marrow and peripheral blood mobilized with granulocyte colony-stimulating factor (G-CSF). The human umbilical cord derived mesenchymal stem cells and the haploidentical umbilical cord blood cells were transferred as third pard of cell. The graft-versus-host disease (GVHD) was prevented with CsA, MTX, ATG, CD25 and mycophenolate mofetil. The results indicated that the infused numbers of MNC and CD34(+) cells of donor were 7.92×10(8)/kg and 3.78×10(6)/kg, respectively. The numbers of neutrophils and platelets were over 0.5×10(9)/L and 20×10(9)/L on days 12 and 14, respectively. On day 35 the chimeras accounted for 94%. No serious complications appeared up to now. In conclusion, the preliminary results suggest that transplantation of haploidentical hematopoietic stem cells combined with two kind of third part cells is safe and satisfactory.

Clinical study on recombinant humanized anti-CD25 monoclonal antibody used for treating steroid-resistant acute graft versus host disease following allo-hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to investigate the efficacy and feasibility of recombinant humanized anti-CD25 monoclonal antibody for treating steroid-resistant acute graft-versus-host disease (aGVHD ) following allo-hematopoietic stem cell transplantation (allo-HSCT) . Twenty-one cases with II-IV grade steroid-resistant aGVHD after allo-HSCT were treated by intravenous injection of recombinant humanized anti-CD25 monoclonal antibody at a dose of 1 mg/(kg·d) on days 1, 4, 8. Injection was repeated after 1 week for the patients who did not achieve CR. The results indicated that 13 cases (61.9%) got complete response (CR), 4 cases out of them have been still in disease-free survival, 8 cases have been in survival with mild cGVHD, 1 cases died from AML relapse, 6 cases (28.57%) got partial response (PR), 3 cases out of them have been in survival with mild cGVHD, 3 case died from pulmonary infection, 2 cases without response died from GVHD. Overall response rate was 90.5% and long term survival rate was 71.48%. There were no infusion-associated side-effects after treatment with recombinant humanized anti-CD25 monoclonal antibody.It is concluded that recombinant humanized anti-CD25 monoclonal antibody is effective and feasible for treatment of steroid-refractory grade II-IV aGVHD after allo-HSCT.

Clinical analysis of high risk and refractory malignant hematologic diseases treated with haploidentical hematopoietic stem cell transplantation combined with umbilical cord mesenchymal stem cells using modified conditioning regimen / 中国实验血液学杂志

This study was aimed to investigate the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) combined with umbilical cord mesenchymal stem cells (MSC) using modified conditioning regimen for the treatment of patients with refractory and relapsed or high risk malignant hematologic diseases, the clinical efficacy in 30 patients with refractory and relapsed or high risk malignant, who voluntarily received HSCT was analyzed. Among the 30 patients there were 4 relapsed cases and 26 cases of high risk malignant hematologic diseases. The above-mentioned patients included 15 AML, 9 ALL, 3 pro T lymphoblast lymphoma/leukemia, 1 spleen boundary zone lymphoma IVB, 1 NK/T lymphoma and 1 Burkitt lymphoma IVB. The results showed that the implantation was achieved in all 30 cases, among them 19 cases (63%) had aGVHD and 6 cases (20%) had III-IV aGVHD, 8 cases (32%) had cGVHD including 1 case of extensive and 7 cases of limited. Three cases relapsed at 300 days (128-455 d) after transplantation. 8 cases died, among them 1 case died of relapse, 2 cases died of IV aGVHD with relapse, 5 cases died of infection and organ failure. It is concluded, the efficacy of hi-HSCT combined with umbilical cord MSC for treatment of patients with refractory and relapsed or high risk malignant hematologic diseases is favorable.

Efficacy of donor's purified CD34(+) cells for treatment of poor graft function following allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to evaluate the efficacy and safety of donor's purified CD34(+) cells for treatment of secondary poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Ten patients suffering from secondary PGF after allo-HSCT in our hospital from January 2009 to December 2011 were treated with the donor's purified and G-CSF mobilized CD34(+) cells. All the patients were observed for infusion-related complication and survival status. CliniMACS system was used to separate cells, the results of sorting purified and recovery rate were calculated and statistically analysed. The results showed that the purified of CD34(+) cells reached to (89.31 ± 1.73)%, and the recovery rate reached to (93.27 ± 8.14)%; 10 patients in the process of infusion did not suffer from seriously adverse complications, all of them obtained hematopoietic recovery, neither GVHD nor infection occurred after infusion of donor's purified CD34(+) cells. It is concluded that using CliniMACS system for donor's peripheral CD34(+) separation, both the purified and recovery of CD34(+) cells are satisfied, and the infusion of donor's purified CD34(+) cell is a safe and effective method to treat secondary PGF after allo-HSCT.

Association between polymorphisms of inflammatory factor genes and coronary heart disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between genetic polymorphisms of inflammatory factors and susceptibility to coronary heart disease(CHD) in southern Chinese Han population.</p><p><b>METHODS</b>Using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) method, the genotypes of five inflammatory factors (BRCA1-associated protein, a disintegrin and metalloproteinase 8, inter-alpha-trypsin inhibitor H3, interleukin-15, cyclooxygenase-2) were anaylzed in 283 CHD patients diagnosed by angiography and 176 controls.</p><p><b>RESULTS</b>In these inflammatory factors, the 270T/C and 90A/G polymorphisms of the BRAP gene showed a significant association with CHD. The allele and genotype frequencies of BRAP gene were consistent with those predicted by Hardy-Weinberg equilibrium (chi-square=0.878, P> 0.05; chi-square=0.776, P> 0.05, respectively). The frequencecies of 270C and 90G alleles in CHD patients was significantly higher than those of the control group (29.51% vs. 21.31%, P=0.006; 30.04% vs. 21.31%, P=0.004, respectively). Compared with 270TT and 90AA, 270CC and 90GG genotypes had a significantly increased CHD risk by Logistic regression analysis (OR=4.51, 95%CI: 1.41-14.45, P=0.011; OR=5.09, 95%CI: 1.60-16.26, P=0.006, respectively). This association was still signifcant after adjustment for the sex, age, smoke, hypertension, diabetes, plasma total cholesterol and low density lipoprotein levels. No evidence of association was found for other single nucleotide polymorphisms.</p><p><b>CONCLUSION</b>The 270T/C and 90A/G polymorphisms in the BRAP gene may contribute to an increased risk of CHD among southern Chinese Han population.</p>

Curative efficacy analysis of allo-HSCT using conditioning regimen of FLAG combined with modified BUCY for refractory and relapsed patients with hematologic malignancies / 中国实验血液学杂志

This study was aimed to investigate the curative efficacy of allogenetic hemopoietic stem cell transplantation (allo-HSCT) using FLAG and modified BUCY conditioning regimen for patients with refractory and relapse or high risk hematologic malignancies. The therapeutic effect of allo-HSCT with FLAG and modified BUCY conditioning regimen on 10 patients with hematologic malignancies was analyzed. 10 patients included 2 cases of relapse (1 early relapse, 1 progression) and 7 cases of refractory (2 CR(2), 1 CR(3) and 2 PR and 1 NR) and 1 CR(1) with high risk. Among 10 cases 8 cases was diagnosed as AML, 1 case as pro-T lymphoblast lymphoma/leukemia and 1 case as spleen marginal zone lymphoma. The results showed that implantation of all the patients was successful. The relapse-free median survival time of 8 cases was 164 days (57 - 442 days) and survived up to now, 2 cases died (1 case died of pulmonary infection, 1 case died of fungus pulmonitis). In conclusion, the curative efficacy of allo-HSCT using FLAG and modified BUCY conditioning regimen for patients with refractory and relapsed hematologic malignancies is satisfactory.

Correlation between loss of heterozygosity on chromosome 1p and 19q and expression of MGMT, p53 and Ki-67 proteins in gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the correlation of loss of heterozygosity (LOH) on chromosome 1p and 19q with the expression of MGMT, p53 and Ki-67 proteins in gliomas.</p><p><b>METHODS</b>One hundred and forty six cases of gliomas (45 oligodendrogliomas, 42 oligodendroastrocytomas, and 59 astrocytomas) were included in this study. Their tissue and blood samples were retrospectively analyzed by PCR-denaturing high-performance liquid chromatography (DHPLC) for 1p and 19q status and by immunohistochemistry for MGMT, p53 and Ki-67 expression patterns. The correlation among them and with clinicopathological characteristics were analyzed by chi-square test and t-test.</p><p><b>RESULTS</b>In the oligodendrogliomas, the positive rate of 1p LOH was 59.8%, significantly higher than 33.9% in astrocytomas (P = 0.002), and 1p and 19q LOH was 42.5%, significantly higher than 16.9% in astrocytomas (P = 0.001). Combined with LOH on 1p and 19q, low MGMT expression (65.5%), and high Ki-67 expression (54%) were more frequent in oligodendrogliomas, whereas high p53 expression was more frequent in astrocytomas and mixed tumors (75.2%). 1p LOH (72.5%) and low MGMT (87.5%) expressions were more frequent in grade II oligodendrogliomas, whereas high expressions of p53 (83.0%) and Ki-67 (76.6%) were more frequent in grade III oligodendrogliomas. In addition, high Ki-67 expression was more frequent in grade III astrocytomas. LOH on 1p and 19q LOH was more frequent in nontemporal oligodendrogliomas (55.6%) than that in temporal ones (22.2%, P = 0.002). Non-random associations were found between LOH 1p and 19q LOH, MGMT and p53 protein expressions, and MGMT and Ki-67 protein expressions (all P < 0.05), whereas mutual exclusions were found between LOH on 1p and 19q and p53 expression, and LOH 1p and Ki-67 expression.</p><p><b>CONCLUSIONS</b>There is a significant interrelationship of the investigated molecular markers and clinicopathological features of gliomas, which support a promising role of molecular markers in guiding diagnostic assessment and clinical management of gliomas.</p>

Effect of dexmedetomidine on patient-controlled intravenous analgesia with fentanyl in elderly patients after total hip replacement / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of a continuous infusion of low-dose dexmedetomidine on patient-controlled analgesia (PCA) with fentanyl in elderly patients after total hip replacement.</p><p><b>METHODS</b>Forty patients (ASA I-II) aged 66-81 years after total hip replacement were randomized equally into the control and test groups. The patients in the test group received continuous infusion of dexmedetomidine at the rate of 0.2 µg·kg(-1)·h(-1) from the beginning to the end of PCA with fentanyl after the surgery, while those in the control group received normal saline. The cumulative fentanyl dose, VAS pain scores and Ramsay sedation score were recorded at 0, 4, 8, 12 and 24 h after the surgery.</p><p><b>RESULTS</b>All the patients in the two groups reported good pain relief and none needed additional fentanyl. The VAS pain score was significantly lower (P<0.05 or 0.01), while the Ramsay sedation scores higher (P<0.05) in the test group than in the control group. The cumulative fentanyl dose was significantly lower in the test group (P<0.05 or 0.01). The incidence of such adverse effects as nausea and vomiting was significantly lower in the test group (P<0.05).</p><p><b>CONCLUSION</b>PCA with fentanyl combined with low-dose dexmedetomidine infusion is safe for elderly patients, and can decrease fentanyl consumption and improve the effect of PCA with fentanyl.</p>

Efficacy of haploidentical allogeneic bone marrow hematopoietic stem cell transplantation combined with umbilical cord blood derived mesenchymal stem cells for severe aplastic anemia / 中国实验血液学杂志

The aim of this study was to investigate the effect of haploidentical allogeneic bone marrow or peripheral blood hematopoietic stem cell transplantation (allo-HSCT) combined with umbilical cord blood mesenchymal stem cell (MSC) infusion in treatment of severe aplastic anemia (SAA). Five SAA patients received haploidentical allo-HSCT combined MSC infusion. HSC and MSC were collected from bone marrow or peripheral blood of haploidentical donors and umbilical cord blood respectively. After transplantation, the clinical hematopoietic reconstitution and early complications were monitored. The results indicated that all the 5 patients achieved hematopoietic reconstitution. The average time for WBC count > 2×10(9)/L was 13.8 days, and average time for Plt level > 20×10(9)/L was 17.8 days. The STR-PCR detection of patient peripheral blood at day 30 after transplantation showed that engraftment was complete donor's gene type. The communication with 1 patient was broken off because of his epilepsy, other 4 patients are all alive in diseases-free state. In conclusion, the haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA, which needs to be further studied in a large number of cases.

Association of the polymorphism of synaptobrevins/vesicle-associated membrane proteins 8 gene with coronary heart disease in Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of synaptobrevins/vesicle-associated membrane proteins 8 (VAMP8) gene rs1010 polymorphism with coronary heart disease (CHD) in Chinese Han population.</p><p><b>METHODS</b>The allele and genotype frequencies of the VAMP8 gene rs1010 locus in 185 CHD patients and 149 controls were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing.</p><p><b>RESULTS</b>There was polymorphism of the VAMP8 gene rs1010 locus in the studied population. The distribution of VAMP8 genotypes was in Hardy-Weinberg equilibrium. The frequency of the A allele in the CHD group was significantly higher than that in control (67.3% vs 53.0%, P< 0.05). Multiple logistic regression analysis showed that genotypes AA and AG were independent risk factors of coronary heart disease. The odds ratio (OR) of (AA+AG) genotype versus GG genotype was 1.969,95% CI: 1.032-3.755.</p><p><b>CONCLUSION</b>The VAMP8 rs1010 polymorphism was associated with CHD risk in Chinese Han population, the A allele might serve as a genetic risk factor of coronary heart disease.</p>