Cytotoxicity of 4 Wild Mushrooms in a Case of Yunnan Sudden Unexplained Death / 法医学杂志

OBJECTIVES@#To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD.@*METHODS@#Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope.@*RESULTS@#Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts.@*CONCLUSIONS@#The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.

Cloning and expression analysis of U6 promoters in Panax quinquefolius / 中国中药杂志

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Auditory response of the reticular nucleus of thalamus in awake mice / 生理学报

This study aims to explore the auditory response characteristics of the thalamic reticular nucleus (TRN) in awake mice during auditory information processing, so as to deepen the understanding of TRN and explore its role in the auditory system. By in vivo electrophysiological single cell attached recording of TRN neurons in 18 SPF C57BL/6J mice, we observed the responses of 314 recorded neurons to two kinds of auditory stimuli, noise and tone, applied to mice. The results showed that TRN received projections from layer six of the primary auditory cortex (A1). Among 314 TRN neurons, 56.05% responded silently, 21.02% responded only to noise and 22.93% responded to both noise and tone. The neurons with noise response can be divided into three patterns according to their response time: onset, sustain and long-lasting, accounting for 73.19%, 14.49% and 12.32%, respectively. The response threshold of the sustain pattern neurons was lower than those of the other two types. Under noise stimulation, compared with A1 layer six, TRN neurons showed unstable auditory response (P < 0.001), higher spontaneous firing rate (P < 0.001), and longer response latency (P < 0.001). Under tone stimulation, TRN's response continuity was poor, and the frequency tuning was greatly different from that of A1 layer six (P < 0.001), but their sensitivity to tone was similar (P > 0.05), and TRN's tone response threshold was much higher than that of A1 layer six (P < 0.001). The above results demonstrate that TRN mainly undertakes the task of information transmission in the auditory system. The noise response of TRN is more extensive than the tone response. Generally, TRN prefers high-intensity acoustic stimulation.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Efficacy and Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Monocytic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute monocytic leukemia (AML-M5) and the related factors that affecting the prognosis of the patients.@*METHODS@#The clinical data of 71 patients with AML-M5 treated with allo-HSCT in Zhujiang Hospital Affiliated to Southern Medical University from April 2009 to October 2019 were collected and retrospectively analyzed. The incidence of graft-versus-host disease (GVHD), cumulative overall survival (OS) rate, cumulative progression-free survival (PFS) rate, transplantation-related mortality (TRM), relapse rate and the risk factors affecting prognosis in the patients were analyzed.@*RESULTS@#66 patients obtained hematopoietic reconstruction after transplantation, the median time of granulocyte implantation was 12 (9-26) d, and the median time of megakaryocytic implantation was 13 (8-72) d. The incidence of acute GVHD and chronic GVHD was 33.8% (24/71) and 36.6% (26/71), respectively. The median follow-up time was 13.81 (0.16 to 112.54) months; the median OS and PFS was 31.27 and 26.07 months, respectively. The cumulative OS of the patients in 1 and 3 years after transplantation was 64.9% and 48.6%, respectively, and the cumulative PFS of the patients in 1 and 3 years was 55.0% and 39.5%, respectively. The cumulative relapse rate of the patients in 1 and 3 years was 24% and 40%, respectively. Multivariate analysis showed that pre-transplantation relapse was the independent risk factor affecting OS (HR=2.32, 95%CI:1.17-4.62, P=0.02) and PFS (HR=3.08, 95%CI:1.61-5.90, P=0.001) of the patients; invasive fungal disease after transplantation was the independent risk factor affecting OS (HR=2.71, 95% CI:1.32-5.56, P=0.007) and PFS (HR=2.87, 95%CI=1.40-5.86, P=0.004) of the patients; FLT3 mutation was the independent risk factor affecting PFS (HR=2.13, 95%CI=1.07-4.24, P=0.03) of the patients.@*CONCLUSION@#AML-M5 is the intermediate or high-risk leukemia, and allo-HSCT can improve the survival prognosis of the patients. Pre-transplantation relapse and invasive fungal disease after transplantation are the important factors affecting the efficacy of allo-HSCT in patients with AML-M5.

Cardiac Disease Associated Genetic Variants in Yi Nationality in Regions with High Incidence of Yunnan Sudden Unexplained Death / 法医学杂志

Objective To explore the association of cardiac disease associated genetic variants and the high incidence of Yunnan sudden unexplained death （YNSUD） in Yi nationality. Methods The genomic DNA was extracted from peripheral blood samples collected from 205 Yi villagers from YNSUD aggregative villages （inpatient group） and 197 healthy Yi villagers from neighboring villages （control group）. Fifty-two single nucleotide variants （SNVs） of 25 cardiac disease associated genes were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. The SPSS 17.0 was used to analyze data. The pathogenicities of variants with differences between the two groups that have statistical significance were predicted by protein function prediction software PolyPhen-2 and SIFT. All villagers from inpatient group were given electrocardiogram （ECG） examination using a 12-lead electrocardiograph. Results The allele frequency and the genotype frequency of missense mutation DSG2 （rs2278792, c.2318G>A, p.R773K） of pathogenic genes of arrhythmogenic right ventricular cardiomyopathy （ARVC） in inpatient group was higher than that in control group （P<0.05）. Abnormal ECG changes were detected in 71 individuals （34.6%） in the inpatient group, among which 54 individuals carried R773K mutation, including clockwise （counterclockwise） rotation, left （right） axis deviation, ST segment and T wave alteration and heart-blocking. Conclusion Definite pathogenic mutations have not been found in the 52 cardiac disease genes associated SNVs detected in Yi nationality in regions with high incidence of YNSUD. The cause of high incidence of YNSUD in Yi nationality needs further study.

Clinical Analysis of Efficacy and Prognosis in 300 Cases of Hematological Malignancies Receiving Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of malignant hematopathy and its influencing factors.@*METHODS@#The clinical data of 300 cases received hematopoietic stem cell transplantation due to malignant hematological diseases in Zhu Jiang Hospital of Southern Medical University from January 2010 to June 2018 were analyzed retrospectively, and the factors affecting hematopoietic reconstruction, disease-free survival (DFS) and overall survival (OS) were compared between haploidentical HSCT and HLA matched HSCT.@*RESULTS@#The hematopoietic reconstitution rate, incidence of GVHD, posttransplant recurrence rate and disease-free survival (DFS) were not statistically different between HLA-metched and haploidentical colorts. However, compared with HLA-matched HSCT group the time of platelet implantation was prolonged, the recurrence-related mortality was higher, and the overall survival (OS) rate was lower in the haploidentical HSCT group. Univariate analyses showed that non-remission before transplantation, and grade Ⅲ, Ⅳ aGVHD were the risk factors for OS in both groups (P＜0.05). The age than 40 years old at the time of transplantation and unrelated donors were risk factors for OS in haploidentical HSCT group (P＜0.05). Multivariate analysis showed that non-remission before transplantation and grade Ⅲ, Ⅳ aGVHD were independent prognostic indictor for OS with relative risk (RR) of 4.4 (95% CI,1.5-13.4), 9.3 (95% CI,2.3-37.0), 11.0 (95% CI,3.2-37.3) (P＜0.05) in HLA-matched HSCT group. Unrelated donor, high-risk group, and gradeⅣaGVHD were independent prognostic indictors for OS with relative risk (RR) of 7.4 (95% CI,2.3-23.1), 2.4 (95% CI,1.3-4.5), 4.1(95% CI,1.6-10.5) (P＜0.05) in haploidentical HSCT group.@*CONCLUSION@#The comprehensive curative effect of HLA-matched HSCT is better than the haploidentical HSCT in hematological malignancies. In haploidentical HSCT the selecting related donor is better than unrelated donors, which required more platelet transfusion support.

Isolation and Identification of Chemical Constituents from Rhizomes of Dendropanax proteus / 中国实验方剂学杂志

The chemical constituents from 95% ethanol extract of Dendropanax proteus rhizomes and their anti-inflammatory activities were investigated. These compounds in 95% ethanol extract of D. proteus rhizomes were isolated and purified by silica gel column chromatography, medium-pressure liquid chromatography, preparative liquid chromatography, etc. Their structures were elucidated based on the spectral data and physicochemical properties. All the compounds were tested for their ability to inhibit lipopolysaccharide (LPS) induced nitric oxide production in the murine microglia BV2 cell line. Nine compounds were isolated from the ethyl acetate fraction of 95% ethanol extract of D. proteus rhizomes, and identified as (-)-syringaresinol (1), (+)-(7S,8S)-1',4-dihydroxy-3,3',5'-trimethoxy-7',8,9'-trinor-8,4'-oxyneoligna-7,9-diol (2), erythro-guaiacylglycerol-β-O-4'-coniferyl ether (3), threo-guaiacylglycerol-β-O-4'-coniferyl ether (4), coniferyl alcohol (5), 7-O-ethylguaiacylglycerol (6), vanillin (7), syringaldehyde (8), and excoecanol B (9). Compounds 2 and 4 showed neuritis inhibitory activity against microglial inflammation factor, their half inhibitory concentrations (IC50) were 5.85, 7.29 μmol ·L-1, respectively. Compounds 1-6,8-9 are isolated from this plant for the first time, compounds 2 and 4 exhibit the potent inhibitory activity.

The Influence of Case Teaching of Forensic Pathology Based on Network Platform on Critical Thinking Skills among Forensic Students / 昆明医科大学学报

Objective The paper aimed to discuss the influence of case teaching of forensic pathology based on network platform on the critical thinking ability of forensic students.Methods Students majoring in forensic were randomly divided into the experimental group and the control group with 20 students per group. According to heterogeneity classification, the experimental group was divided into 4 subgroups. The subgroups participated in network cases learning whereas the control group received traditional case teaching. Participants were required to fill in California Critical Thinking Disposition Inventory-Chinese Version (CCTDI-CV) before and after learning. CCTDI-CV scores, the scores of final exam and the number of students who had improved in CCTDI-CV scores were compared between the two groups. Results For the experimental group, the total score of CCTDI-CVand the scores of items including looking for the truth, systematized ability, self-confidence, thirst for knowledge were significantly improved after learning. The performance of the experimental group was better than that of the control group at the end of teaching (P＜0.05) . The scores of final exam were higher in the experimental group compared to the control group (P＜0.05) .Conclusion Forensic pathology cases teaching based on network platform is an effective way to stimulate students'critical thinking ability and to improve the study ability.

Treatment of Recalcitrant Plantar Warts with 5-aminolevulinic Acid Photodynamic Therapy(ALA-PDT)after Preconditioning with Superpulse Carbon Dioxide Laser / 中山大学学报(医学科学版)

[Objective]To investigate the efficacy and safety of ALA-PDT following CO2laser preconditioning for recal-citrant plantar warts.[Methods]Patients with recalcitrant plantar warts were enrolled in this study,and received ALA-PDT treatment following CO2laser preconditioning. Cure rate and side effects were observed.[Results]Twenty patients were en-rolled and 85%(17/20)showed complete clearance of plantar warts after one to three times of ALA-PDT. PDT treatment time was once in two patients(10%),twice in five patients(25%)while three times in 10 patients(50%).No infection or scar tissue was observed.Five(25%)patients were infected with one type of HPV,while 15(75%)patients with two or mul-tiple types of HPV. No difference was observed in complete clearance rate between patients with single or multiple HPV gen-otypes infection.[Conclusions]Superpulse carbon dioxide laser pretreatment enhanced the efficacy of ALA-PDT treatment on recalcitrant plantar warts.Further study is needed to determine the association of HPV genotype with outcome of recalci-trant plantar warts.

Research progress of pharmacological effects of mulberroside / 中国药理学通报

Mulberroside, a glycosylated stilbene, is the main bioactive constituent of white mulberry root-bark ( Sangbaipi) . It is widely used in many famous traditional Chinese medicine pre-scriptions to treat gout, arthritis, and rheumatism through pur-ging diuresis and relieving edema. In recent years, the pharma-cological activity of mulberroside has drawn extensive attention. With the utilization of the techniques and methods of modern pharmacology, a variety of biological activity and pharmacologi-cal effects of mulberroside are discovered gradually. The recent progress in the research on pharmacological effects of mulberro-side was reviewed in this paper to provide reference for the fur-ther development and comprehensive utilization.

Effect of Silencing Eps8 Gene Expression on the Biology Activity of Human Leukemia K562 Cells and Its Molecular Mechanism / 中国实验血液学杂志

<p><b>OBJECTIVE</b>The study was to investigate the effect of silencing Eps8 gene expression on proliferation and apoptosis of human leukemia K562 cells and its molecular mechanism.</p><p><b>METHODS</b>The expetriments were divided into 3 groups, including blank control group(K562 cells without treatment), K562-shRNA group(K562 cells transfected by specific Eps8-shRNA lenticiral vector) and K562-NC group(K562 cells transfected by negtive control lenticiral vector). K562 cells with stably-silenced Eps8 gene were constucted by lentibirus-mediated RNA technology. The efficacy of transfection was observed by fluorescence microscopy and the changes of Eps8 mRNA and protein level were detected by RT-PCR and Western blot respectively. Cell proliferation was confirmed by typan blue exclusion and MTT method. The apoptosis rate of cells was analysed by the flow cytometry, and colony forming was detected by methylcellulose colony forming assay. The protein level change of phosphrylated-AKT were detected by Western blot.</p><p><b>RESULTS</b>Stably-silenced Eps8 gene K562 cells and the negative control cells were successfully constructed. Compared with the blank control group and the K562-NC group, the proliferation of K562-shRNA cells were siginificantly inhibited(P<0.05); the apoptosis of K562-shRNA cells increased(P<0.05). In addition, the methylcellulose colony forming assay showed that the colony forming was dramatically suppressed in K562-shRNA cells (P<0.05). Furthermore, knocking down Eps8 gene reduced the protein level of AKT phosphrylation at both residue Ser437 and Thr308(P<0.05), while there was no obvious change in the level of total-AKT(P>0.05). Knocking down Eps8 gene reduced the protein level of m-TOR phosphrylation and PRAS40 phosphrylation (P<0.05), while there was no obvious change in the level of total-mTOR and PRAS40 (P>0.05).</p><p><b>CONCLUSION</b>Silencing Eps8 gene through lentvirus can inhibit the cell proliferation and promote the apoptosis of human leukemia K562 cells, which possibly relates with the inhibition of AKT/mTOR activation.</p>

Regulation of P-glycoprotein gene expression by PKC/NF-κB-PXR signaling pathway / 药学学报

P-glycoprotein (P-gp), an ATP binding cassette protein, plays a major role in efflux transport of drugs and xenobiotics due to its abundant expression on several barriers. This study aimed to investigate the potential role of PKC/NF-κB-PXR signaling pathway in modulation of P-gp gene expression in human colon adenocarcinoma LS174T. The effect of PMA on MDR1 luciferase activity was investigated by PXR-MDR1 dual luciferase reporter gene assay. Real-time qPCR assay and Western blot analysis were used to study the gene expression of P-gp and NF-κB, respectively. Compared to the vehicle-treated group, PMA statistically decreased P-gp luciferase activity, mRNA expression and protein expression. Moreover, PMA treatment yielded a significant and dose-dependent increase in RelA/p65 translocation to nucleus. Meanwhile, a remarkable increase of the pho-IκBα status was observed in LS174T cells after treatment with PMA (1-100 nmol·L-1). In addition, knockdown of PKCα, NF-κB or PXR can significantly attenuate PMA-induced P-gp suppression.These results suggested that PKC/NF-κB-PXR signaling pathway might play crucial roles in modulation of P-gp gene expression.

Prediction and Identification of HLA-A*0201 Restricted CTL Epitopes from Eps8 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To find and identify HLA-A*0201 restricted cytotoxic T lymphocyte (CTL) epitopes from epidermal growth factor pathway substrate number 8 (Eps8) for specific immunotherapy based on Eps8-derived epitopes in clinic.</p><p><b>METHODS</b>Online biological softwares involved C-proteasomal cleavage, MHC class I binding affinity and TAP transport efficiency were used for prediction of HLA-A*0201 restricted epitopes from Eps8. Then, T2-binding assays and peptide/MHC complex stability tests were used to further verify the predicted epitopes. Specific secretion of IFN-γ from human CTL was assayed using the IFN-γ ELISPOT kit, and cytolytic activity was measured by a 4-h lactate dehydrogenase (LDH) release assay. Finally, the functional effects in vivo were measured in HLA-A*0201/Kb transgenic (Tg) mice.</p><p><b>RESULTS</b>Four natural epitopes were designed through online biological softwares. Of the four epitopes selected, p360-368 was found to have the high binding affinity to HLA-A*0201, while p101-109 and p276-284 showed moderate affinities. DC50 of peptide/MHC complexes of the natural epitopes mentioned were all longer than 8 h. In functional assays with human PBMNC in vitro and in HLA-A*0201/Kb transgenic mice in vivo, CTLs primed by each epitope (p101-109, p276-284 and p360-368) secreted IFN-γ and were toxic to cancer cells from a variety of tissue types in an HLA-A*0201-restricted and Eps8-specific manner.</p><p><b>CONCLUSION</b>Natural epitopes (p101-109, p276-284 and p360-368) may be the HLA-A*0201 restricted epitope derived from Eps8.</p>

Research Progres on Relationship between the Graft-Versus-Host Disease and Cytomegalovirus Infection--Review / 中国实验血液学杂志

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of leukemia patients can improve overall survival and disease-free survival, and reduce relapse. Although the allo-HSCT is more widely used in the treatment of leukemia, but the graft-versus-host disease (GVHD) and cytomegalovirus (CMV) infections are the common complications, and are the major cause of mortality for patients following allo-HSCT. Previous studies showed that there might be a mutual promotive relationship between GVHD and CMV infection, but the clear relationship remained to be elucidated. The relationship of GVHD and CMV has been the focus of clinical research. Recently, a great progress has been made on researches of the relationship and its mechanism between GVHD and CMV infection. In this article, the relationship and its mechanism between GVHD and CMV infection after allo-HSCT are reviewed.

Clinical Summarization of Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia: A Report of 100 Cases / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the treatment outcome of a consecutive series of 100 leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of leukemia patients received allo-HSCT were analyzed retrospectively, the therapeutic efficacy was summarized. 100 evaluable cases of leukemia included 47 cases of AML, 33 cases of ALL, 2 cases of AL (biphenotypic), 16 CML and 2 CMML. Before transplantation, 76 cases were in first complete remission, 9 cases in second or greater complete remission and 15 cases in non-remission or relapse. All the patients received peripheral blood hematopoietic stem cell transplantation (PBHSCT). The conditioning regimen of human leukocyte antigen (HLA)-matched allo-HSCT group was modified BuCy, but in HLA-mismatched group Fludarabine and anti-human thymocyte globulin (ATG) was added. CsA+MTX regimen was used for prophylaxis of graft-versus-host disease (GVHD) in HLA-identical allo-HSCT, while additional MMF was added in HLA-mismatched group. The average time of follow-up was 13 months.</p><p><b>RESULTS</b>At the last follow-up, 66.0% (66/100) patients survived, 53.0% (53/100) patients survived without leukemia, 28.0% (28/100) patients relapsed and 34.0% (34/100) patients died, 44.1% patients of them died from infectious pulmonary complications. During transplantation, 65.0% of the patients were suffered from lung infection. The overall survival (OS) and disease-free survival (DFS) of all cases was 60.9% and 48.8%, respectively. The recurrence rate was significantly higher in non-remission (66.7%) than in CR (21.2%) patients (P < 0.05). The cumulative incidence of GVHD in HLA-mismatched transplantation was 60.8%, which was significantly higher than that of HLA-matched transplantation (38.8%) (P < 0.05).</p><p><b>CONCLUSION</b>Allo-HSCT can cure a significant proportion of leukemia patients, especially for those in CR status. Since the incidence of infectious pulmonary complications after allo-HSCT is still high, much more attention should be paid to it. The comprehensive prognosis of HLA-matched transplantation is better than the HLA-mis-matched transplantation.</p>

Progress of Clinical Trials on Bone Marrow Mesenchymal Stem Cells for Prevention and Therapy of Graft-Versus-Host Disease / 中国实验血液学杂志

Graft-versus-host disease (GVHD) is a major complication following allogenetic hematopoietic stem cell transplantation, which shows a great threat to patients' survival and life quality. Along with multiple differentiation potential to various types of progenitor cells, bone marrow mesenchymal stem cells (BMMSC) have been confirmed to possess low immunogenicity and exert favorable immunomodulation. The recent studies show that the safety and high efficiency of BMMSC to prevent and cure GVHD greatly improved survival rate of the hosts. The most recent progress on prevention and therapy of GVHD is summarized in this review based on biology of BMMSC and pathogenesis of GVHD, so as to provide the effective evidence for further research.

Effect of Brucea javanica fruit oil emulsion combined cisplatin on the growth inhibition of transplanted tumor in human ovarian cancer SKOV3 nude mice: an experimental study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice.</p><p><b>METHODS</b>Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot.</p><p><b>RESULTS</b>The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05).</p><p><b>CONCLUSIONS</b>Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.</p>

Correlation of IKZF1 Gene with Malignant Tumors and Systemic Lupus Erythematosus / 中国实验血液学杂志

IKZF1 gene located in 7p12 of chromosome, and Ikaros family zinc finger encoded by IKZF1, are lymphoid-restricted transcription factors. In recent years, it has been demonstrated that the mutation of IKZF1 gene involved in proliferation, metastasis and prognosis of many malignant tumor except acute lymphoblastic leukemia, and also involved in complex phenotypes and susceptibility to systemic lupus erythematosus. This review briefly introduces the molecular structure and physiological function of Ikaros, focusing on its function and molecular mechanism in proliferation, metastasis and prognosis of malignant tumors, and its role in the systemic lupus erythematosus.

Efficacy of Donor Lymphocyte Infusion for Treating Relapsed High-Risk Leukemia patients after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of donor lymphocyte infusion (DLI) for treating relapsed high-risk leukemia patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The data of 15 leukemia patients who had received DLI and 13 leukemia patients who had not received DLI in Zhujiang Hospital from 2000 to 2014 were studied retrospectively, and their 1 and 3 year overall survival rate (OS) were compared between the two groups.</p><p><b>RESULTS</b>In 15 patients received DLI, the 1 and 3 year OS were 58.3% and 46.7%, the 1 and 3 year disease-free survival (DFS) were 22.0% and 11.0%, respectively. The main death cause in these patients included relapse (n = 5) and acute GVHD (n = 1), whereas in 13 patients who had not received DLI, the 1 and 3 year OS were 29.9% and 15.0% respectively, their 1 year DFS were 11.2%. The main death cause in these patients were relapse (n = 9). The 1 and 3 year OS of patients who had received DLI was higher as compared with the patients who had not received DLI. but this difference was no statistically significant (P = 0.069).</p><p><b>CONCLUSION</b>DLI is an effective method for treating patients with relapsed leukemia, and may improve the therapeutic efficacy of DLI by combining other methods or alternating the types of the donor lymphocytes.</p>