Regressive vision transformer for dog cardiomegaly assessment.

Cardiac disease is one of the leading causes of death in dogs. Automatic cardiomegaly detection has great significance in helping clinicians improve the accuracy of the diagnosis process. Deep learning methods show promising results in improving cardiomegaly classification accuracy, while they are still not widely applied in clinical trials due to the difficulty in mapping predicted results with input radiographs. To overcome these challenges, we first collect large-scale dog heart X-ray images. We then develop a dog heart labeling tool and apply a few-shot generalization strategy to accelerate the label speed. We also develop a regressive vision transformer model with an orthogonal layer to bridge traditional clinically used VHS metric with deep learning models. Extensive experimental results demonstrate that the proposed model achieves state-of-the-art performance.

Venetoclax in adult acute myeloid leukemia.

Venetoclax is a potent inhibitor that specifically targets B-cell lymphoma-2 (BCL-2), which has been demonstrated to be effective in preclinical studies utilizing acute myeloid leukemia (AML) cell lines and xenograft models. Significant antileukemic activity was also observed in clinical trials, both as a monotherapy and in combination with other drugs. This novel therapeutic approach has revolutionized the treatment prospects for AML patients with unfavorable prognoses and those who are unable to tolerate intensive chemotherapy. Nevertheless, further investigations are required to establish the optimal dosing, sequencing, and combinational strategies of venetoclax for AML treatments. Additionally, identifying biomarkers is crucial for predicting response and resistance to this targeted intervention. In this review, we provide an overview of venetoclax-based therapy for AML and explore potential avenues for future research.

The efficacy and safety of eltrombopag in treating TKI-induced thrombocytopenia in patients with chronic myeloid leukemia.

ABSTRACTThrombocytopenia is one of the most common hematological adverse reactions in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKI) therapy, causing life-threatening bleeding cases. However, there are fewer therapeutic drugs for TKI-induced thrombocytopenia. Eltrombopag is a non-peptide thrombopoietin receptor agonist used for the treatment of immune thrombocytopenia， aplastic anemia, and hepatitis C-associated thrombocytopenia. Nevertheless, studies of eltrombopag for TKI-induced thrombocytopenia are still lacking. This study retrospectively analyzed the clinical and test data of 21 CML patients with TKI-related thrombocytopenia. The results demonstrated that the median baseline value of thrombocytopenia in the 21 CML patients was 15.57 × 109/L [2-28 × 109/L]. Following treatment with eltrombopag, 16 patients had a significant increase in their platelet levels. The peak median for platelet increase in effective responders was 145.12 × 109/L (51-460 × 109/L). However, 5 patients failed to respond to eltrombopag. Moreover, 4 of the 21 patients enrolled had adverse reactions, including reversible liver function impairment, palpitation, headache, insomnia, and loss of appetite. Nonetheless, no cases of disease progression, thrombotic events, or myelofibrosis were observed. Hence, eltrombopag may be a useful adjunctive therapy for relieving TKI-related thrombocytopenia in patients with CML.

Artificial intelligence 101 for veterinary diagnostic imaging.

The prevalence and pervasiveness of artificial intelligence (AI) with medical images in veterinary and human medicine is rapidly increasing. This article provides essential definitions of AI with medical images with a focus on veterinary radiology. Machine learning methods common in medical image analysis are compared, and a detailed description of convolutional neural networks commonly used in deep learning classification and regression models is provided. A brief introduction to natural language processing (NLP) and its utility in machine learning is also provided. NLP can economize the creation of "truth-data" needed when training AI systems for both diagnostic radiology and radiation oncology applications. The goal of this publication is to provide veterinarians, veterinary radiologists, and radiation oncologists the necessary background needed to understand and comprehend AI-focused research projects and publications.

Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China.

Background: To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. Objective: To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. Methods: We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. Results: A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. Conclusion: The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown; the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

Lightweight mobile network for real-time violence recognition.

Most existing violence recognition methods have complex network structures and high cost of computation and cannot meet the requirements of large-scale deployment. The purpose of this paper is to reduce the complexity of the model to realize the application of violence recognition on mobile intelligent terminals. To solve this problem, we propose MobileNet-TSM, a lightweight network, which uses MobileNet-V2 as main structure. By incorporating temporal shift modules (TSM), which can exchange information between frames, the capability of extracting dynamic characteristics between consecutive frames is strengthened. Extensive experiments are conducted to prove the validity of this method. Our proposed model has only 8.49MB parameters and 175.86MB estimated total size. Compared with the existing methods, this method greatly reduced the model size, at the cost of an accuracy gap of about 3%. The proposed model has achieved accuracy of 97.959%, 97.5% and 87.75% on three public datasets (Crowd Violence, Hockey Fights, and RWF-2000), respectively. Based on this, we also build a real-time violence recognition application on the Android terminal. The source code and trained models are available on https://github.com/1840210289/MobileNet-TSM.git.

Comparisons of Modified Post-Transplantation Cyclophosphamide and Granulocyte Colony-Stimulating Factor/Antithymocyte Globulin Regimens for Haploidentical Stem Cell Transplantation in Patients with Aplastic Anemia.

Haploidentical stem cell transplantation (HSCT) has become an alternative treatment option for patients with aplastic anemia (AA) without matched sibling donors or matched unrelated donors. Recently, post-transplantation cyclophosphamide (PTCy) and granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG) regimens have become the most common protocols used worldwide. In this retrospective study, we retrospectively reviewed and analyzed the clinical data of 130 AA patients who underwent haploidentical HSCT and received the modified PTCy (mPTCy) regimen (n = 55) or G-CSF/ATG regimen (n = 75) between January 2013 and June 2021 across 7 transplantation centers. Neutrophil engraftment was successful in all patients within 30 days in the G-CSF/ATG group. The cumulative neutrophil engraftment rate in the mPTCy group was 96.36% (95% confidence interval [CI], 94.57 to 97.57; P = .010). The median time to neutrophil engraftment in the G-CSF/ATG group was 10 days (range, 7 to 28 days), which was more rapid than that observed in the mPTCy group (P < .001). There was no significant difference in the incidence of graft-versus-host disease (GVHD) between the 2 groups. The cumulative incidence of grade II-IV acute GVHD was 18.40% (95% CI, 4.27% to 40.31%) in the mPTCy group and 19.32% (95% CI, 5.86% to 38.58%) in the G-CSF/ATG group, whereas the cumulative incidence of grade III-IV acute GVHD was 7.31% (95% CI, .09% to 37.48%) in the mPTCy group and 7.57% (95% CI, .20 to 34.19) in the G-CSF/ATG group. Similarly, there were no significant between-group differences in overall survival (OS), failure-free survival (FFS), and GVHD-free relapse-free survival (GRFS). The 2-year OS, FFS, and GRFS rates were 95.91% (95% CI, 84.59% to 98.96%), 92.25% (95% CI, 80.59% to 97.03%), and 86.68% (95% CI, 73.98% to 93.44%), respectively, in the mPTCy group and 86.67% (95% CI, 76.64% to 92.59%), 81.28% (95% CI, 70.45% to 88.46%), and 77.20% (95% CI, 65.89% to 85.16%), respectively, in the G-CSF/ATG group. Transplantation-related mortality (TRM) was significantly higher in the G-CSG/ATG group than in the mPTCy group (13.33% versus 1.96%; P = .022). In multivariate analysis, the use of a female donor, a higher Hematopoietic Cell Transplantation Comorbidity Index, and grade III-IV acute GVHD were associated with worse survival outcomes. The mPTCy and G-CSF/ATG regimens led to similar outcomes in AA patients, but quicker engraftment was observed with the ATG/G-CSF regimen, and a lower incidence of TRM was observed with the mPTCy regimen.

Separable Confident Transductive Learning for Dairy Cows Teat-End Condition Classification.

Teat-end health assessments are crucial to maintain milk quality and dairy cow health. One approach to automate teat-end health assessments is by using a convolutional neural network to classify the magnitude of teat-end alterations based on digital images. This approach has been demonstrated as feasible with GoogLeNet but there remains a number of challenges, such as low performance and comparing performance with different ImageNet models. In this paper, we present a separable confident transductive learning (SCTL) model to improve the performance of teat-end image classification. First, we propose a separation loss to ameliorate the inter-class dispersion. Second, we generate high confident pseudo labels to optimize the network. We further employ transductive learning to narrow the gap between training and test datasets with categorical maximum mean discrepancy loss. Experimental results demonstrate that the proposed SCTL model consistently achieves higher accuracy across all seventeen different ImageNet models when compared with retraining of original approaches.

Identification and construction of lncRNA-associated ceRNA network in diabetic kidney disease.

ABSTRACT: Diabetic kidney disease (DKD) has become the major contributor to end-stage renal disease with high incidence and mortality. The functional roles and exact mechanisms of long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network in DKD are still largely unknown. This study sought to discover novel potential biomarkers and ceRNA network for DKD.The candidate differentially expressed genes (DEGs), lncRNAs and microRNAs (miRNAs) in human glomerular and tubular tissues derived from Gene Expression Omnibus database were systematically selected and analyzed. Functional enrichment analysis and protein-protein interaction network analysis were conducted to identify hub genes and reveal their regulatory mechanisms involved in DKD. Following this, the integrated ceRNA network was constructed by bioinformatics methods.A total of 164 DEGs, 6 lncRNAs and 18 miRNAs correlated with DKD were finally filtered and identified. It is noteworthy that the global lncRNA-associated ceRNA network related to DKD was constructed, among which lnc-HIST2H2AA4-1, VCAN-AS1 and MAGI2-AS1 were identified as the 3 key lncRNAs, and VCAN, FN1, CCL2, and KNG1 were identified as the predominant genes. Consistent with that observed in the training set, 3 of the key genes also showed significant differences in the 2 validation datasets. Integrating with functional enrichment analysis results, these key genes in the ceRNA network were mainly enriched in the immune and inflammation-related pathways.This study first identified key lncRNAs, miRNAs and their targets, and further revealed a global view of lncRNA-associated ceRNA network involved in DKD by using whole gene transcripts analysis.

Study on the efficient removal of azo dyes by heterogeneous photo-Fenton process with 3D flower-like layered double hydroxide.

As organic dyes are the main pollutants in water pollution, seeking effective removal solutions is urgent for humans and the environment. A novel environmentally friendly three-dimensional CoFe-LDHs (3D CoFe-LDHs) catalyst was synthesized by one-step hydrothermal method. Scanning electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectra, X-ray diffraction, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller technique as well as UV-Vis diffuse reflectance spectra were used to characterize the prepared samples. The experimental results revealed that 3D CoFe-LDHs exhibited a rapid decolorization of methyl orange and Rhodamine B by heterogeneous photo-Fenton process after reaching the adsorption equilibrium, and the final decolorization efficiency reached 91.18% and 93.56%, respectively. On the contrary, the decolorizing effect of 3D CoFe-LDHs on neutral blue was relatively weak. The initial concentrations of azo dyes, pH and H2O2 concentration affected the decolorization of dyes and the catalyst maintained excellent reusability and stability after reuse over five cycles. The quenching experiments found that •OH, •O2 - and h+ were the main active substances and reaction mechanisms were further proposed. The study suggests that the synergistic effect of photocatalysis and Fenton oxidation process significantly improved the removal of azo dyes and the synthesized catalyst had potentially promising applications for difficult-to-biodegrade organic pollutants in wastewater.

COVID-19 in persons with chronic myeloid leukaemia.

We studied by questionnaire 530 subjects with chronic myeloid leukaemia (CML) in Hubei Province during the recent SARS-CoV-2 epidemic. Five developed confirmed (N = 4) or probable COVID-19 (N = 1). Prevalence of COVID-19 in our subjects, 0.9% (95% Confidence Interval, 0.1, 1.8%) was ninefold higher than 0.1% (0, 0.12%) reported in normals but lower than 10% (6, 17%) reported in hospitalised persons with other haematological cancers or normal health-care providers, 7% (4, 12%). Co-variates associated with an increased risk of developing COVID-19 amongst persons with CML were exposure to someone infected with SARS-CoV-2 (P = 0.037), no complete haematologic response (P = 0.003) and co-morbidity(ies) (P = 0.024). There was also an increased risk of developing COVID-19 in subjects in advanced phase CML (P = 0.004) even when they achieved a complete cytogenetic response or major molecular response at the time of exposure to SARS-CoV-2. 1 of 21 subjects receiving 3rd generation tyrosine kinase-inhibitor (TKI) developed COVID-19 versus 3 of 346 subjects receiving imatinib versus 0 of 162 subjects receiving 2nd generation TKIs (P = 0.096). Other co-variates such as age and TKI-therapy duration were not significantly associated with an increased risk of developing COVID-19. Persons with these risk factors may benefit from increased surveillance of SARS-CoV-2 infection and possible protective isolation.

Accuracy and Safety of Lateral Vertebral Notch-Referred Technique Used in Subaxial Cervical Pedicle Screw Placement.

BACKGROUND: Biomechanical studies revealed that pedicle screw instrumentation has a superior stabilizing effect compared with other internal fixations in reconstructing the subaxial cervical spine. However, severe neurovascular risks preclude surgeons from routinely conducting pedicle screw manipulation in cervical spine. OBJECTIVE: To evaluate the accuracy and safety of the lateral vertebral notch (LVN)-referred technique used in subaxial cervical pedicle screw (CPS) placement. METHODS: One hundred thirty-five consecutive retrospective patients with cervical disorders underwent the LVN-referred technique for CPS placements in 3 spine centers. Postoperative pedicle perforations were confirmed by CT scans to assess the technical accuracy. Neurovascular complications derived from CPS misplacements were recorded to evaluate the technical safety. RESULTS: A total of 718 CPSs were inserted into subaxial cervical spine. Postoperative CT scans revealed that the accuracy of CPS placement was superior. Neither vertebral artery injury nor spinal cord injury occurred. One radiculopathy was from a unilateral C6 nerve root compression. A screw-related neurovascular injury rate of 0.7% occurred in this cohort. Additionally, there was no significant difference in the accuracy of CPS placement among 3 surgeons (H = 1.460, P = .482). The relative standard deviation values revealed that technical reproducibility was acceptable. Furthermore, there was no significant difference between the patients' pedicle transverse angles and inserted CPS transverse angles from C3 to C7 (all P > .05). CONCLUSION: The LVN is a reliable and consistent anatomic landmark for CPS placement. The accuracy and safety of subaxial CPS placement by using LVN-referred technique are highly acceptable, which may endow this technique to be practicably performed in selected patients.

[Relation between single Nucleotide Polymorphisms of CYP3A5 Gene and MDR1 Gene Loci and Risk of CML Cytogenetic Relapse].

OBJECTIVE: To analyze the relation between the signle nucleotide polymorphisms (SNP) of CYP3A5 gene and MDR1 gene loci and the risk of cytogenetic relapse in chronic myeloid leukemia (CML). METHODS: The clinical data of 90 patients with CML treated with imatinib in our hospital were collected.The patients were divided into 2 groups: non-relapse and relapse according to relapse and non-relapse, then the relation between the SNP of CYP3A5 gene and MRD1 gene loci and the risk of cytogenetic relapse in CML patients. RESULTS: The grouping result showed that the patients with non cytogenetic relapse accounted for 41 cases those were enrolled in non-relapse group, and patient-with cytogenetic relapse accounted for 49 cases those were enrolled in relapse group. The follow-up time was 36 months. The detection showed that the incidence of cytogenetic relapse in the patients with CC genotype was significantly higher than that in the patients with TT+CT genotype of C3435T and C1236T at MDR1 gene loci (P<0.05).Compared with the patients with CT+CC genotype in C3435T locus of MDR1 gene, the rate of cytogenetic relapse in the patients with TT genotype decreased significantly (P<0.05). Compared with patients with CT+CC phemotype of C3435T in MDR1 gene locus, the non-relapse survival time of TT genotypes was significantly prolonged (P<0.05). Compared with non-relapse group, the incidence of neutropenia (29.27% vs 71.43%) and blood toxicity (39.02% vs 61.22%) in the relapse group increased significantly (P<0.05). The imatinib dose (OR=2 95, 95% CI:1.37~7.76) and the C3435T genotype in MDR1 genes (OR=0.09, 95% CI:0.05~0.72) were the factors affecting the cytogenetic relapse of the patients with CML (both P<0.05). CONCLUSION: The therapeutic dose of imatinib and the C3435T and C1236T genotypes in MDR1 gene have a certain effect on the cytogenetic relapse of CML patients. C3435T genotypes in the.MDR1 gene showed a certain predictive value for evaluating the risk of cytogenetic relapse, which can be used as a clinical biomarker.

Automated Identification of Hookahs (Waterpipes) on Instagram: An Application in Feature Extraction Using Convolutional Neural Network and Support Vector Machine Classification.

BACKGROUND: Instagram, with millions of posts per day, can be used to inform public health surveillance targets and policies. However, current research relying on image-based data often relies on hand coding of images, which is time-consuming and costly, ultimately limiting the scope of the study. Current best practices in automated image classification (eg, support vector machine (SVM), backpropagation neural network, and artificial neural network) are limited in their capacity to accurately distinguish between objects within images. OBJECTIVE: This study aimed to demonstrate how a convolutional neural network (CNN) can be used to extract unique features within an image and how SVM can then be used to classify the image. METHODS: Images of waterpipes or hookah (an emerging tobacco product possessing similar harms to that of cigarettes) were collected from Instagram and used in the analyses (N=840). A CNN was used to extract unique features from images identified to contain waterpipes. An SVM classifier was built to distinguish between images with and without waterpipes. Methods for image classification were then compared to show how a CNN+SVM classifier could improve accuracy. RESULTS: As the number of validated training images increased, the total number of extracted features increased. In addition, as the number of features learned by the SVM classifier increased, the average level of accuracy increased. Overall, 99.5% (418/420) of images classified were correctly identified as either hookah or nonhookah images. This level of accuracy was an improvement over earlier methods that used SVM, CNN, or bag-of-features alone. CONCLUSIONS: A CNN extracts more features of images, allowing an SVM classifier to be better informed, resulting in higher accuracy compared with methods that extract fewer features. Future research can use this method to grow the scope of image-based studies. The methods presented here might help detect increases in the popularity of certain tobacco products over time on social media. By taking images of waterpipes from Instagram, we place our methods in a context that can be utilized to inform health researchers analyzing social media to understand user experience with emerging tobacco products and inform public health surveillance targets and policies.

Chiral PEDOT-Based Enantioselective Electrode Modification Material for Chiral Electrochemical Sensing: Mechanism and Model of Chiral Recognition.

The development of electrochemical methods for enantioselective recognition is a focus of research in pharmaceuticals and biotechnology. In this study, a pair of water-soluble chiral 3,4-ethylenedioxythiophene (EDOT) derivatives, (R)-2'-hydroxymethyl-3,4-ethylenedioxythiophene ((R)-EDTM) and (S)-2'-hydroxymethyl-3,4-ethylenedioxythiophene ((S)-EDTM), were synthesized and electrodeposited on the surface of a glassy carbon electrode (GCE) via current-time (I-t) polymerization in an aqueous LiClO4 electrolyte. These chiral PEDOT polymers were used to fabricate chiral sensors and to investigate the enantioselective recognition of d-/l-3,4-dihydroxyphenylalanine, d-/l-tryptophan, and (R)-/(S)-propranolol enantiomers, respectively. The results indicated that the (R)-PEDTM/GCE sensor showed a higher peak current response toward the levo or (S) forms of the tested enantiomers, while the opposite phenomenon occurred for (S)-PEDTM/GCE. The mechanism of the stereospecific interaction between these enantiomers and the chiral polymers was determined. Therefore, a model of the chiral recognition by the chiral conducting polymer electrodes and an electrochemical method was proposed. The chirality of the enantiomers was confirmed by two parameters: the chirality of the electrode and the peak current response. These findings pave the way for the application of chiral PEDOT as electrode modification material in the electrochemical chiral recognition field.

Porcine antilymphocyte globulin (p-ALG) plus cyclosporine A (CsA) treatment in acquired severe aplastic anemia: a retrospective multicenter analysis.

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome characterized by pancytopenia and hypocellular bone marrow. Antithymocyte globulin (ATG) is the drug of choice for immunosuppressive therapy (IST) in patients with SAA ineligible for allogeneic stem cell transplantation. This study aimed to evaluate the efficacy and safety profile of porcine antilymphocyte globulin (p-ALG) plus CsA in the treatment of acquired SAA. Clinical information of 69 SAA patients treated with p-ALG plus CsA was collected and retrospectively analyzed for early mortality, response rate, survival rate, side effects, and other complications. The median age at diagnosis was 27 years (range 14 to 52). The overall response rate was 76.8 % with a 90-day median response time (range 30 ~ 360 days). Overall response rates at 3, 6, 12, 18, and 24 months were 63.8, 73.9, 76.8, 75.4, and 75.4 %, respectively. The median follow-up time for surviving patients was 24 months (range 4 ~ 44 months) and the 2-year overall survival (OS) rate was 88.4 %. The disease-free survival (DFS) rate at 2 years was 85.5 %. Older age (≥45 years), very (v)SAA subgroup, and lower baseline absolute lymphocyte count (<1 × 10(9)/L) were independent unfavorable predictors of overall survival (p < 0.05). Less than one third of patients had serum sickness or allergic reaction during ALG therapy, but symptoms could easily be relieved by steroid treatment; 27.54 % had mild hepatic impairment. Taken together, p-ALG showed similar efficacy and safety profiles to rabbit or horse ATG in IST of acquired SAA. It can be a suitable alternative preparation for rabbit ATG with the great advantage of lower medical expenses.

Evaluation of a rapid and convenient method for determination of cytomegalovirus immunoglobulin M.

We evaluated a method for determination of human cytomegalovirus (hCMV) immunoglobulin M (IgM) by CLIA, and analyzed its clinical value in patients with infectious mononucleosis. Serum samples from 407 participants were measured on an automatic CLIA analyzer. At the same time the serum samples were measured by enzyme-linked immunosorbent assay (ELISA). An assessment of technological quality (methodology) in diagnostic tests demonstrated that the sensitivity of CLIA was 1.0 AU/mL and the functional sensitivity was <1.6 AU/mL. The within- and between-assay imprecision values for different concentrations were all under 5%. Recoveries for both methods were 96-110%. The linear regression equation between expected values and measured values was y=0.644+0.986x, and correlation coefficient was 0.9991 (P<0.0001). The receiver operating characteristic (ROC) curve showed that both the sensitivity and specificity of CLIA surpassed 90%. The area under the curve (AUC) was 0.990, which was significantly higher than that of ELISA (P<0.05). The results indicate that CLIA is an excellent method for hCMV IgM measurement, and thus may be useful for clinical diagnoses.

Study on blocking the leukemia immune escape after BMT by Fas-Fas ligand pathway.

BACKGROUND: To investigate if bone marrow transplantation (BMT) with bone marrow mononuclear cells (BMMCs) transducted with murine soluble Fas gene (sFas) using adenovirus vector could block the immune escape of leukemia cells eliminate the residual leukemia cells and reduce their relapse. METHODS: The recombinant adenovirus vector with murine sFas, adsFas, and the control vector adEGFP were constructed using homologous recombination between two plasmids in Escherichia coli. BMT was carried out after the BMMCs were infected with Adenoviruses. The mice models of leukemia/lymphoma were constructed by inoculating female C57BL/6 mice (H-2b) with 10(5) EL4 cells/mouse through caudal vein. Donors of bone marrow grafts were syngeneic male mice. BMMCs were infected with AdsFas or AdEGFP 24 hours before (Group D or E). The following three groups were simultaneously used: Group A, no BMMCs transplanted; Group B, transplanted with BMMCs not infected with adenoviruses; Group C, only transfusing EL4 cells, neither irradiation nor BMT. The hematopoietic reconstitution, generation of leukemia/lymphoma and the survival rate were observed in all groups after BMT. RESULTS: The adenovirus vectors were successfully constructed. The titre of virus after purification was up to 2.5 x 10(11) pfu/ml. Spleen indices examined 11 days after BMT were not obviously different among Group B, D and E (P > 0.05), but indices in Group A were significantly lower than those in the latter three groups (P < 0.01). Counts of leukocytes and platelets on +30 day showed mice were reconstituted satisfactorily in Group B and D, but very low in Group C and E. The Y-chromosomes existed 2 months after BMT and examination of bone marrow cytology showed that Group B and D were almost normal, but Group C and E had plenty of lymphoblast-like tumor cells. Tumors were obviously observed in the mice of Group C and E by histopathological examination, but the mice in Group B and D were normal. The survival rates were 0 (0/4) in Group A, 100% in Group B (6/6) and D (16/16), 12.5% (2/16) in Group C and 6.25% (1/16) in Group E respectively. It is demonstrated that, in contrast with the control (Group EGFP), survival rate was significantly increased in the sFas Group (P < 0.01). CONCLUSIONS: The transfer of sFas gene by adenovirus changed the prognosis state of leukemia/lymphoma mice after auto-BMT. The transduction of sFas might block the effect of the immune escape of EL4 cells through FasL. These results could thus provide a new direction to find a way to treat the leukemia and its recurrence after BMT.

[Experimental study on blocking immune escape of leukemia cells in the recipient after bone marrow transplantation].

OBJECTIVE: To investigate whether murine soluble Fas gene transfected marrow graft could block the immune escape of leukemia cells, so as to eliminate the residual leukemia cells and reduce relapse after bone marrow transplantation (BMT). METHODS: The murine leukemia/lymphoma models were established by inoculating female C57BL/6 mice (H-2b) with 10(5) EL4 cells/mouse through caudal vein. Donors of BM grafts were C57BL/6 male mice. Bone marrow mononuclear cells (BMMCs) were transfected with sFas or EGFP by adenovirus (adsFas or adEGFP) 24 hours before BMT (group D or E). The following three groups were set simultaneously: group A, no BMMCs transplanted; group B, BMMCs transplanted with no adenoviruses transfection; group C, EL4 cells transfusion only. Hematopoietic reconstitution, generation of leukemia/lymphoma and the survival rate were observed in all the groups after BMT. RESULTS: The spleen indices examined 11 days after BMT were not obviously different among group B, D and E (P > 0.05), but in group A were significantly lower than those in the groups B, D, E (P < 0.01). The leukocyte and platelet counts on day 30 after BMT were recovered in group B and D, but were very low in group C and E. The Y-chromosomes appeared 2 months after BMT. Bone marrow pictures in group B and D were almost normal, but in group C and E had plenty of lymphoblast-like tumor cells. Tumors were obviously revealed in the mice of group C and E by histopathology examination, but did not in group B and D. The survival rate was 0 in group A, 100% in group B and D, 12.5% in group C and 6.25% in group E. Compared with that in group E, the survival was significantly increased in the sFas group (P < 0.01). CONCLUSIONS: Graft transfected with sFas gene prolonged the post-BMT survival of leukemia/lymphoma mice. The transfection of sFas might block the effect of the immune escape of EL4 cells through FasL.