Correlation between three-dimensional histogram analysis of dynamic contrast-enhanced MRI and Gleason score in prostate cancer / 中华老年医学杂志

Objective:To investigate the correlation between three-dimensional histogram analysis of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and Gleason score(GS)in prostate cancer(Pca)from two hospital, and its diagnostic efficacy for discriminating low-grade from high-grade Pca.Methods:A total of 102 pathologically confirmed Pca patients in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Traditional Chinese Medical Hospital(TCM Hospital)Affiliated to Zhejiang Chinese Medical University from January 2017 to October 2020 were retrospectively analyzed.The quantitative parameters of Pca, including transport constant(K trans), rate constant(K ep), percent volume of the extravascular extracellular space(V e)and fraction of the Intraplasmic contrast volume(V p), were obtained by manually layer by layer delineating of interested regions of all lesions on the original DCE-MRI imaging.Then the three-dimensional histogram analysis of the above parameters were performed to obtain the minimum, maximum, median, mean, area, 10 thpercentile, 25 thpercentile, 75 thpercentile and 90 thpercentile.The correlations between quantitative parameters and GS, and diagnostic efficiencies were analyzed. Results:102 Pca patients were divided into low-grade prostate cancer group(GS≤3+ 4)(n=44)and high-grade Pca group(GS≥4+ 3)(n=58). There were no statistically significant differences in age and location of lesions between the two groups( P>0.05), but there were statistically significant differences in Gleason score, PSA level and lesion diameter between the two groups( U=0.000, 730.000, 711.000, all P<0.05). The median, mean, 10 thpercentile, 25 thpercentile, 75 thpercentile, 90 thpercentile derived from K trans, and K ep(median, mean, 10%, 25%, 75%, 90%)together with maximum of K transand mean for V e were positively correlated with GS( r=0.405 to 0.583, P<0.05), in which mean of K transhad the highest positive correlation( r=0.583, P=0.000). The histogram parameters derived from V pwere negatively correlated with GS( r=-0.301 to 0.341, P<0.05). The area under ROC of 75th percentile derived from K transwas the highest(0.832). When the cut-off value of 75 thpercentile derived from K transwas ≥0.680/min, its Youden index, sensitivity, and specificity were 0.594, 0.776, 0.818, respectively. Conclusions:The three-dimensional histogram of DCE-MRI quantitative parameters has correlation with GS in Pca patients, can be used to discriminate low-grade from high-grade Pca.

Effects of total parenteral nutrition on drug metabolism gene expression in mice

Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid® and omega-3 rich Omegaven® are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. In this study, either Intralipid®- or Omegaven®-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed, glutathione (GSH) levels were measured, and protein levels for two key drug metabolism genes were determined. Overall, the expression of most genes was downregulated by Intralipid®-based TPN ( and ). Omegaven® showed similar results as Intralipid® except for preserving the expression of and and increasing . Total GSH levels were decreased by Intralipid®, but increased by Omegaven®. CYP3A11 protein levels were increased by Omegaven®. In conclusion, TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice. However, Omegaven® preserved expression of , suggesting another beneficial effect of Omegaven® in protecting liver functions.

Advances in the treatment of newly diagnosed primary central nervous system lymphomas

Primary central nervous system lymphoma (PCNSL) is a type of highly invasive non-Hodgkin lymphoma. With a growing number of organ transplantation and immunosuppressant therapy, the incidence of PCNSL has been growing rapidly in recent years, which is attributed to the increased incidence of HIV/AIDS, a prominent risk factor for developing PCNSL. The rising rate of PCNSL incidence is the highest among the intracranial tumors. In the past 20 years, dozens of clinical trials related to PCNSL have been registered, but adequate therapeutics are still challenging. Currently, the chemotherapy regimens based on high-dose methotrexate and whole-brain radiotherapy are the two main therapeutic options; however, the toxicity associated with those is the main problem that challenges medical researchers. Novel agents and therapeutic strategies have been developed in recent years. In the current review, we describe advances in the treatment of PCNSL and discuss novel therapeutic approaches currently in development, such as the use of rituximab, disruption of the blood-brain barrier, and state-of-the-art radiotherapy.

Role of tyrosine kinase inhibitor in induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective To explore the feasibility of low-dose chemotherapy (LDCT) combined with tyrosine kinase inhibitor (TKI) (LDCT+TKI regimen) as the first-line induction regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL).Methods The efficacies and adverse effects of various induction regimens in 61 newly diagnosed patients with Ph+ ALL were retrospectively analyzed.Results The complete remission (CR) rate of the first induction therapy was 73.8 ％ (45/61) for all 61 cases,and that of the second induction therapy was 86.7 ％ (13/15) for non-remission (NR) patients after the first induction.The total CR rate for two-course induction was 95.1％ (58/61).Treatment related mortality happened in one case (1.6 ％) after the first induction therapy.The response rates between conventional-dose chemotherapy (CDCT)±TKI group and LDCT±TKI group were not statistically different [without TKI,65.5 ％ (19/29) vs 60.0 ％(3/5),P =0.812;with TKI,90.5 ％ (19/21) vs 100.0 ％ (6/6),P =0.432].The response rate of LDCT+TKI group was not statistically different from that of CDCT alone group (P =0.089).The introduction of TKI to LDCT and CDCT could improve the response rate (CDCT+TKI group,P =0.041;LDCT+TKI group,P =0.087).The total response rate of the induction therapy with TKI was significantly higher than that without TKI [92.6 ％ (25/27) vs 64.7 ％ (22/34),P =0.01].The response rate of the TKI-based second induction therapy for non-CR cases after the first induction therapy without TKI was significantly higher than that after the first induction therapy with TKI [100.0 ％ (8/8) vs 33.3 ％ (1/3),P =0.011].There were no significant differences in the efficacies of the first induction therapy between various genetic subgroups (all P ＞ 0.05),and the introduction of TKI to the treatment of various genetic subgroups could improve the efficacies to a certain extent without statistical significance (all P ＞ 0.05).The incidences of treatment related infections and bleeding due to the first induction therapy in all patients were 50.8 ％ (31/61) and 4.9 ％ (3/61),respectively.Compared with LDCT±TKI group,the overall incidences of treatment related infections and bleeding in CDCT±TKI group were higher,but there were no statistical significances [infection,56.0 ％ (28/50) vs 27.3 ％ (3/11),P =0.084;bleeding,6.0 ％ (5/30) vs 0 (0/1 1),P =0.405].The incidence of treatment related infections in LDCT+TKI group was significantly lower than that in CDCT+TKI group [0 (0/6) vs 71.4 ％ (15/21),P =0.002] or that in CDCT alone group [0 (0/6) vs 44.8 ％ (13/29),P =0.039].The incidence of bleeding in LDCT+TKI group was not statistically different from that in CDCT+TKI group or that in CDCT alone group (all P ＞ 0.05).Conclusion LDCT+TKI regimen as the first-line induction regimen in Ph+-ALL is deserved to be investigated further.

Screening and Characterization of Human Phage Antibody to Permethrin / 现代检验医学杂志

Objective To do screening acute lymphoblastic leukemia patients scFv antibody single chain variable region to cre-ate conditions for the expression and obtain further specificity of antibody fragments.Methods In this study,patients with newly diagnosed acute lymphoblastic leukemia serum as coating antigen using phage display technology,screening phage an-tibody specificity from the semi-synthetic human phage antibody libraries,the first to target the immune antigen-coated tab-let,phage library was added,so that with the target antigen-specific binding phage antibody was immobilized on plates immu-nization,could not be specifically bound phages were rinsed.The eluted specific binding phage,E.coli infection.Could get the specific antibody gene containing phagemid.Results After three “adsorption-elution-amplification”screening process,got stronger leukemia patient antigen-specific phage antibody variable region fragment and identification.Conclusion Got better strain affinity antibody fragments,to create the conditions for the next fragment expression,identification and clinical appli-cation.

Clinical analysis of HAA induction regimen for newly diagnosed and refractory relapsed acute myeloid leukemia / 白血病·淋巴瘤

Objective To analyze the efficacy and safety of HAA induction regimen consisted of homoharringtonine (HHT),cytarabine (Ara-C) and aclacinomycin (ACM) in naive and refractory relapsed acute myeloid leukemia.Methods Data from 66 acute myeloid leukemia (AML) cases hospitalized and treated with HAA induction regimen was analyzed retrospectively.Results 45 of the 66 cases suffered from naive AML,and 21 were refractory relapsed.HAA efficacy in naive AML was evaluated in 41 cases with 36 in complete remission (CR) and 1 in partial remission (PR).The efficiency of HAA induction regimen was 90.2 ％ (37/41)in naive AML group and 42.9 ％ (9/21) in refractory relapsed group,respectively.There were no differences (P ＞ 0.05) when considering patient' s gender,age,disease subtype and white blood cell count at onset.14 patients in CR with naive AML were followed-up for a median time of 9 months (2-17 months),and 5 cases relapsed (35.7 ％) in a range of 2-8 months.The median myelosuppression period was 14 days (3-23 days).Nausea and vomiting [20 ％ (13/66)] were the major side effects of HAA regimen,and the other side effects were abdominal pain and diarrhea [9 ％ (6/66).After chemotherapy,53 ％ (35/66) of the cases experienced infection/fever due to neutropenia.Other severe non-hematological side effects did not occur.Conclusion HAA regimen may be an ideal choice for the induction chemotherapy of naive and relapsed refractory AML.

The value of the current diagnostic criteria of pulmonary invasive fungal infection after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To analyze the practicality of current diagnostic criteria of invasive fungal infection (IFI) in patients with hematologic diseases/malignant tumors,so as to enhance the recognition of characteristics of pulmonary IFI after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical features of 51 cases with IFI after allo-HSCT were analyzed retrospectively.Results Pulmonary IFI accounted for 42.1％ (51/121) of the whole infectious pneumonia diagnosed among the patients admitted during the study.One (2.0％) case was proven diagnosis ; 24 (47.1％) were probable diagnosis and 26(51.0％) were possible diagnosis.The using of immuno-suppressors and corticosteroids,and the presence of graft-versus-host disease (GVHD) were the main host factors.The patients with two or more host factors simultaneously accounted for 66.7％ (34/51) of all pulmonary IFI patients.Totally 94.1％ (48/51) of the patients with pulmonary IFI presented nodules and/or patches as the main features in high resolution computed tomography (HRCT) scanning.The positive rates of fungal antigen detection were 58.6％ for G test and 33.3％ for GM test,which were relatively high.Twenty patients (39.2％) showed decrease of arterial partial pressure of oxygen and hypoxia in blood-gas analysis.Conclusions For the diagnosis of pulmonary IFI post allo-HSCT,the administration of immuno-suppressors and corticosteroids,and the presence of GVHD were the main host factors.Nodules and/or patches were the main features in HRCT image.Fungus antigen detection is the main tool to support clinical diagnosis.

Screening and characterization of human phage antibody to permethrin / 中国医师杂志

Objective To screen permethrin human single-chain variable region (scFv) antibody for aims of developing rapid detection kit. Methods Phage display technology was used in this study. Permethrin was solid phase coated on Nunc plate as antigen. Semi-synthetic single-chain variable region of human antibody library technology was applied, and single chain variable region was screened from phage antibody library after 3 rounds "adsorption - elution - amplification" of the selection process. 100 clones were random selected as resistance to permethrin clones , enzyme-linked immunosorbent assay (ELISA), crossreactivity and competitive inhibition experiments were used to validate permethrin binding activity with strong scFv clones from the selected phage antibody clones plasmid. The plasmid was digested with restriction enzyme Sfi Ⅰ / Not Ⅰ and subcloned into pCANTAB5E vector. After transformed into E. coli XL1BIue, the plasmid was identified by restriction enzyme analysis. Results After screening in 100 clones, 18 clones had high ELISA absorbance values ( A value) at 490nm wavelength ( A490nm), then bovine serum albumin (BSA) cross-reactions identified five weak cross-reaction. Combined with the triplicate ELISA and competitive inhibition experiment results, one positive clone was acquired at last. And this clone was subcloned into pCANTAB5E vector and transformed into competent cells XL1-Blue. Conclusion Plasmid fragment was consistent with the purpose, which provided the foundation for further study of its specific affinity.

Research progress of myeloproliferative disorders: several clinical problems post the JAK2 mutation era / 白血病·淋巴瘤

This critical review was summarized more systematically about the JAK2V617F mutation of related research progress in myeloproliferative disorders (MPD) research fields and the identification of JAK2V617F mutation represents an important advance in our understanding of MPD was agreed. The authors focused on several sensitive problems of post the JAK2 mutation era, and expressed their opinions. The Guideline of the MPD diagnostic criteria recommended by WHO in 2008 was accepted. The authors recommend the MPD, rather than myeloproliferative neoplasm (MPN). The treatment for the MPD (not including the CML) is recommended. Before the effective targeting of JAK2V617F specific inhibitors for the treatment of the MPD, short-term of use hydroxyurea (HU) was suggested to suppress excessive proliferation of bone marrow of MPD and a long course of treatment application of inteferon-α(IFN-α), and low-dose of aspirin in a timely manner were recommended to prevent thrombosis and other complications.

Comparison of biological characteristics of mesenchymal stem cells derived from bone marrow, peripheral blood and cord blood / 中国组织工程研究

BACKGROUND:Mesenchymal stem cells (MSCs) exist in human tissues.Presently,cell source is single;culture method has great differences;obtained results are not consistent.Thus,it cannot verfy that isolated and cultured cells are identical calls,which is difficult to compare.OBJECTIVE:To compare the biological features of MSCs derived form bone marrow (BM),perpheral blood (PB) and cord blood (CB) under in vitro culture conditions.DESIGN,TIME AND SETTING:The cytological in vitro controlled study was performed at the Department of Hematology,Navy General Hospital of Chinese PLA from June 2007 to December 2008.MATERIALS:A total of 10 donors of hemopoietic stem cell transplantation at the Department of Hematology,Navy General Hospital of Chinese PLA were selected.MB and PB cells were obtained from the same donor,and cell volumes were respectively 20 mL and 2 mL.CB cells (30 mL) were obtained from healthy primipara at the Department of Obstetrics,Navy General Hospital of Chinese PLA.METHODS:MSCs were obtained from BM,PB and CB by Percoll density gradient + adherence method,and then incubated in DMEM/F12 medium containing 10% fetal bovine serum.When 80%-90% confluency,cells were digested in trypsin-EDTA and made into 5×10~8/L cell suspension as P_0.Above-described operation was performed as P_1,and the rest may be deduced by analogy as P_2-P_5.MAIN OUTCOME MEASURES:The following parameters were measured:cell growth morphology;results of Wright-Giemsa staining;results of cytochemistry;cell proliferation amount;cell surface markers using flow cytometry.RESULTS:Time of adherence,time to 50% confluency and time to 80% confluency of BMSCs were earlier comarped with the PBMSCs and UCMSCs.Adherent cells from BM grew in whirpool-like type,while CB and PB did not at 5-7 days.Majority of aderent cells from BM were fibroblast-like cells,and small parts were endothelioid cells.Aderent cells from PB and CB at the fifth generation contained more endothelioid cells and mononuclear and macrophage-like cells besides fibroblast-like cells.PAS stain,Sudan black B stein,alkaline phosphatase (AKP) staining of adherent cells from BM,PB and CB were negative from P_1 to P_5.Compared with P0 cells,number of BMMSCs till P5 was significantly more in PBMSCs and UCMSCs (P ＜ 0.05).Positive rates of CD29,CD44,CD90,CD71,CD105,CD166 and HLA-ABC were 55.9% 92.8% at P0 to P5,but ≤6% following BMMSCs were incubated;19.7%-33.4% at P0 to P5,but ≤10% following PBMSCs were incubated;35.4%-93.2% at P_0 to P_5,but ≤20% following CBMSCs were incubated.Positive rates of CD34,CD45 and HLA-DR were low in BM-,PB-and CB-MSCs.Positive rates of CD14 and CD31 were low in BMMSCs;12.1%-28.3% in PBMSCs,and 8.1%-21.3% in CBMSCs.CONCLUSION:MSCs can be attained from BM,PB and CB.Quantities of MSCs form BM are the highest,with single component,followed by CBMSCs and PBMSCs,with multiple components.

Treatment with plasma in canine abdominal wurds combined with seawater immersion / 解放军医学杂志

Objectives To explore the effects of hyperosmosis of sea water and low temperature on hemorrhage and coagulation sys- tem of dogs after open abdominal injury followed by sea water immersion,and to observe the efficiency of plasma in addition to routine first aid,so as to provide a theoretical basis for the early treatment of open abdominal wound in naval warfare.Methods 24 dogs with open in- jury of the abdomen were randomly divided to three groups with 8 animals for each group.The dogs in control group were not subjected to sea water immersion and received routine treatments;dogs in conventional therapy group were immersed in sea water and then given the routine first aid;dogs in plasma group were immersed with aqua marina and then given a combined treatment of routine first aid plus an in- fusion of plasma.The following parameters were measured and recorded:survival time,body temperature,mean arterial blood pressure, osmotic pressure of plasma,prothrombin time,partial thromboplastin time,d-dimer and factorⅡ.Results Prothrombin time and partial thromboplastin time were significantly prolonged,D-Dipolymer increased and factorⅡdecreased after sea immersion with open abdominal wound.The survival time of dogs in plasma group(45.6?12.5h)was significantly longer than that of dogs in both control and conven- tional therapy groups(P

The stimulative effects of cord blood serum on hematopoietic cells in vitro / 中国免疫学杂志

Objective:To study the effects of human CBS(Cord Blood Serum) on hematopoietic cells culture in vitro.Methods:CBS and/or different combinations of cytokines were added to the culture system derived from human bone marrow mononuclear cells.Colony forming capacity of colony forming unit-granulocyte/ monocyte (CFU-GM)?colony forming unit-granulocyte/ erythrocyte/ megakaryocyte/ monocyte (CFU-GEMM)?cobble-stone area forming cells (CAFC)?long-term culture initiating cells (LTC-IC) were observed.Results:CBS had certain cytokine-like stimulating activity that could promote the proliferation and differentiation of hematopoietic cells of bone marrow in vitro. By comparison with cytokines, its GM-CSF-like activity was equal to 65.6 ?g/L rhGM-CSF, and its IL-3-like activity was equal to 2.9 ?g/L rhIL-3.Conclusion:CBS contains stimulating activities for proliferating and differentiating of hematopoietic cells. CBS alone can maintain hematopoietic cells culture in vitro. This study showed the prospect of clinical application of CBS.

Effect of Estriol Sodium Succinate on Colony-Stimulating Factor Level in the Serum of Mice / 第二军医大学学报

We studied the changes of colony-stimu lating factor (CSF) level, the type of CSF after intraperi-toncal injection of estriol sodium succinate (E3?SNa) and the effect of E3?SNa itself on the proliferation of bone marrow precursors with the use of both agar colony assay and [3H]-TdR incorporation assay. Our experiment shows that CSF was at high level 6 h after E3?SNa administration and reached a peak by 24 h, and that elevation of CSF in the serum was maintained for at least 30 d. Using 0.14-28 mg of E3?SNa there was a dose-dependent increase in serum CSF when tested 24 h after E3?SNa treatment. The main type of CSF was GM-CSF. There was no direct stimulation of E32?SNa itself on the proliferation of mouse bone marrow precursors. So we think that the effect of estrogens on the hematopoiesis may, at least in part, be mediated by altered CSF activity.