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This study reports the diagnosis and treatment of 2 children with isolated testicular recurrence (ITR) of acute B lymphoblastic leukemia (B-ALL) treated with CD 19 targeted chimeric antigen receptor T (CD 19 CAR-T) cells in May and December 2019 in the Department of Hematology and Oncology, Children′s Hospital of Soochow University, and explores the efficacy of CD 19 CAR-T cells therapy versus conventional radiotherapy and chemotherapy through literature review.Both cases were diagnosed as B-ALL by the morphologic, immunologic, cytogenetic and molecular biology methods.ITR was diagnosed by testicular biopsy at 60 months and 38 months after initial diagnosis in 2 cases, respectively.After infusion of CD 19 CAR-T cells at 7.0×10 6/kg and 1.5×10 7/kg, respectively for 7-10 days, testicular leukemia cell infiltration disappeared and complete remission was obtained.Among them, case 2 developed cytokine release syndrome and immune effector cell-related neurotoxicity syndrome after treatment, which was improved after drug intervention.It is suggested that CD 19 CAR-T cells are effective in the treatment of ITR in children, which may be an alternative to orchiectomy or local radiotherapy for ITR in children with B-ALL.
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A scientific appointment-driven outpatient service proves vital for the medical quality improvement initiative, and a key part of public hospital reform as well. The authors introduced the approaches taken by Northern Jiangsu People′s Hospital as follows. The hospital-wide appointment-drive service was coordinated in terms of top-level design, appointment items, appointment channels, supporting services, and monitoring regulations. This service could optimize the allocation of medical resources, enrich the connotation of appointment for registration, examination, bed, examination, operation and treatment. These efforts were expected to provide references for the implementation of overall management of the appointment-driven service of the hospital.
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PURPOSE: The aim of this study was to explore the function of microRNA-27b (miR-27b) in fibroblast-like synoviocytes (FLSs) stimulated by tumor necrosis factor α (TNF-α). MATERIALS AND METHODS: mRNA expression of miR-27b in FLS cells (MH7A) treated with or without TNF-α was determined by q-PCR. MiR-27b mimics was transfected into MH7A cells to upregulate miR-27b expression. MTT assay and flow cytometry analysis were performed to investigate the effect of miR-27b on MH7A cell viability and apoptosis. The targets of miR-27b were predicted by TargetScan. The direct regulation of miR-27b on IL-1β expression was verified by luciferase assay. The protein expression levels of apoptosis-related proteins, IL-1β, and NF-κB signaling-related proteins were detected by Western blot. RESULTS: We discovered that miR-27b expression was decreased in MH7A cells stimulated by TNF-α. Upregulation of miR-27b by miR-27b mimics significantly inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated MH7A cells. Consistently, upregulation of miR-27 decreased the level of Bcl-2 and increased Bax and caspase-3 expression in MH7A cells stimulated by TNF-α. Luciferase assay revealed that IL-1β was indeed a target of miR-27b. By quantitative real-time PCR and Western blot, we found that the expression of IL-1β is negatively regulated by miR-27b. Moreover, the NF-κB signaling pathway was significantly inhibited by miR-27b. CONCLUSION: Taken together, our results illustrated that enhanced miR-27b expression results in the suppression of proliferation and the promotion of apoptosis in FLSs stimulated by TNF-α, partially by regulating IL-1β expression and NF-κB signaling.
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Apoptosis , Arthritis, Rheumatoid , Blotting, Western , Caspase 3 , Cell Survival , Flow Cytometry , Luciferases , Real-Time Polymerase Chain Reaction , RNA, Messenger , Tumor Necrosis Factor-alpha , Up-RegulationABSTRACT
Objective To investigate clinical features of hair collar sign in children and their implications.Methods Children with confirmed hair collar signs were collected from Department of Dermatology,Children's Hospital of Chongqing Medical University between January 2014 and December 2017.The morphology,distribution and quantity of skin lesions and auxiliary examination results were analyzed retrospectively in 15 patients with complete clinical records.Results The center of skin lesions manifested as a round cystic lesion or a slightly depressed atrophic patch or plaque with lack of hair on the surface of the lesions.The lesions were surrounded by thick and long hair in 13 patients.The skin lesions occurred on the parietal lobe in 9 patients,and on occipital or temporal region in other patients.Of the 15 patients,14 had solitary lesions,and 1 had multiple lesions.Six patients were complicated by nevus flammeus.Brain magnetic resonance imaging examination of 11 patients revealed abnormalities in 2,including 1 with potential skull defect and brain tissue bulging,and 1 with cystic changes on the outer side of the cranial plate.B-mode ultrasound of the brain was performed in 4 patients,and no abnormality was found.Conclusions The skin lesions of hair collar sign are various,and most are solitary lesions.It mostly occurs on the parietal lobe,and is often complicated by nevus flammeus.This sign may suggest the presence of central nervous system malformation in patients.
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Objective To observe the curative effect of Bushen-Tongdu decoction combined with percutaneous minimally invasive decompression for degenerative lumbar spinal stenosis. Methods A total of 80 patients with degenerative lumbar spinal stenosis were selected and divided into two groups of 40 cases by random number table. The control group was treated with percutaneous transforaminal minimally invasive decompression. The treatment group was given Bushen-Tongdu decoction on the basis of the control group. Both groups were treated for 14 days. The Japanese orthopedic Society back pain evaluation criteria for waist pain, leg pain and numbness, walking ability, sensory dysfunction, dyskinesia, straight leg raising test score were collected and compared. Results The total effective rate was 95.00％ (38/40) in the treatment group and 82.50％ (33/40) in the control group. The total effective rate of the two groups was statistically significant (Z=-2.357,P=0.018). After treatment, the levels of waist pain score, leg pain and numbness score, walking ability score, sensory dysfunction score, dyskinesia score and the straight leg raising test score in the treatment group were significantly higher than those in the control group(t=-2.180, -2.059, -1.985, -2.177, -2.045, -2.238, P<0.05).Conclusions The Bushen-Tongdu decoction combined with percutaneous minimally invasive decompression can reduce pain, improve walking ability, improve sensory and motor dysfunction, and improve clinical efficacy of the patients with degenerative lumbar spinal stenosis.
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Objective@#To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell.@*Methods@#The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay.@*Results@#①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8+ T cell acquired dim expression of CD4 membrane protein after activation. CD4+T cell and CD8+CD4dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01).@*Conclusions@#CD4 targeted CAR-T has an immunophenotype of CD8+CD4-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4+T cell and CD4+T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4dim target cell.
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Objective To compare cortical bone screwing and Endobutton plating for the treatment of ankle joint fracture complicated with injury to the distal tibiofibular syndesmosis. Methods Fifty-eight pa-tients with ankle joint fracture and injury to the distal tibiofibular syndesmosis were treated at Department of Orthopedic Surgery, The Affiliated Hospital to Guangdong Medical University from January 2014 to June 2016. Half of them were treated by conventional cortical bone screwing. They were 16 males and 13 females with an average age of 43.2 ± 4.1 years. The other half were treated by Endobutton plating. They were 15 males and 14 females with an average age of 44.1 ± 3.9 years. The 2 groups were compared in terms of intraoperative bleed-ing, operation time, tibiofibular clear space ( TBCS ) , tibiofibular overlap ( TBOL ) , the American Orthopedic Foot Ankle Society (AOFAS) ankle-hindfoot scale and complications. Results The cortical bone screwing group needed significantly shorter operation time (63.4 ± 5.4 min) than the plating group (89.6 ± 6.2 min) ( P ＜0.05) . There were no significant differences between the 2 groups in intraoperative bleeding ( 68.9 ± 6.3 mL versus 67.4 ± 6.4 mL ) , TBCS ( 4.6 ± 0.3 mm versus 4.7 ± 0.3 mm) , TBOL ( 7.5 ± 0.4 mm versus 7.4 ± 0.4 mm ) , good to excellent rate by AOFAS score ( 72.4% versus 75.9%) , or rate of complications ( 6.9% versus 10.3%) ( P ＞ 0.05 ). Conclusion Since cortical bone screwing and Endobutton plating show no signifi-cant difference for the treatment of ankle joint fracture complicated with distal tibiofibular syndesmosis injury, a proper surgical procedure should be decided according to the specific conditions of the patient.
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Objective To summarize the clinical features of graft failure (GF)after non-T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HCT), and to investigate the causes and treatment. Methods A retrospective analysis was carried out on 174 patientswho accepted the non-T-cell depleted Haplo-HCT from Jan 2012 to Dec 2013. The patients′ donor specific anti human leukocyte antigen antibodies (DSA) from the peripheral blood serum were detected and those DSA positive patients were treated by immunoglobulin or plasma exchange before transplatation. Results A total of three patients with acute myeloid leukemia got GF, the incidence rate was 1.72%. The patient with primary GF was given a secondHaplo-HCT, but did not get implanted with leukemia remission and three lineages persistently low , he was died of pulmonary infection eight monthes after the second transplant. One of the secondary GF patients was given peripheral blood mononuclear cells(PBMNCs) mobilized by granulocyte colony stimulating factor (G-CSF) from the donor, and got full donor chimerism on day 16 after infusion. The disease-free survival has been for 18 months. The other case was found that DSA was positive, the mean fluorescence intensity (MFI) value was 15000, then Rituximab and PBMNCs mobilized by G-CSF were administrated successively. On day 14 after infusion the partient got full donor chimerism , and MFI turned negative. The patient has been disease-free survival for 41 months. Conclusion Graft failure is a rare but fatal complication after non-T-cell depletedHaplo-HCT, Rituximab followed by PBMNCs are effective measures for DSA related GF, as were worthy of further study.
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<p><b>OBJECTIVE</b>To investigate the correlation between CMV reactivation and obliterative bronchiolitis (BO) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>From January 2011 to December 2013, 769 patients underwent allo-HSCT. The CMV infection was diagnosed by fluorescence quantitative PCR method for detecting the level of CMV-DNA and immunofluorescence staining of PP65 antigen in white blood cell. The frequency of BO in patients with and without CMV infection was compared, and the correlation between CMV infection and BO was analyzed. The clinical data of CMV infection patients with and without BO were analyzed and compared.</p><p><b>RESULTS</b>Of 259 diagnosed CMV infection patients, BO occurred in 32 cases, the incidence rate was 12.35%, while in 510 cases without CMV infection, BO occurred in 8 cases, the incidence was 1.56%. The incidence rate of BO is significantly higher in patients with CMV infection than that in patients without CMV infection (P<0.001). The CMV related clinical data between the 32 cases with BO and 227 cases without BO were analyzed among the 259 cases of diagnosed CMV infection patients. BO incidence is higher in patients with more than 10⁵ copies/ml CMV-DNA than that in patients with less than 10² copies/ml CMV-DNA.</p><p><b>CONCLUSION</b>Among the risk factors related to BO post allo-HSCT, CMV infection is one of them to be worthy of attention. CMV reactivation with high virus titer, multiple CMV reactivations and CMV pneumonia are the risk factors.</p>
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Humans , Allografts , Bronchiolitis , Bronchiolitis Obliterans , Cytomegalovirus , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Real-Time Polymerase Chain Reaction , Risk Factors , Viral Load , Virus ActivationABSTRACT
A 54-year-old female patient with congenital heart disease had a persistent complete left bundle branch block three months after closure by an Amplatzer ventricular septal defect occluder. Nine months later, the patient suffered from chest distress, palpitation, and sweating at daily activities, and her 6-min walk distance decreased significantly (155 m). Her echocardiography showed increased left ventricular end-diastolic diameter with left ventricular ejection fraction of 37%. Her symptoms reduced significantly one week after received cardiac resynchronization therapy. She had no symptoms at daily activities, and her echo showed left ventricular ejection fraction of 46%and 53%. Moreover, left ventricular end-diastolic diameter decreased 6 and 10 months after cardiac resynchronization therapy, and 6-min walk dis-tance remarkably increased. This case demonstrated that persistent complete left bundle branch block for nine months after transcatheter closure with ventricular septal defect Amplatzer occluder could lead to left ventricular enlargement and a significant decrease in left ventricular systolic function. Cardiac resynchronization therapy decreased left ventricular end-diastolic diameter and increased left ventricular ejection fraction, thereby improving the patient’s heart functions.
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<p><b>OBJECTIVE</b>To investigate the role of imatinib in induction therapy for newly diagnosed adult patients with Philadephia chromosome-positive acute lymphoblastic leukemia (Ph⁺ALL), as well as the status of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of adult Ph⁺ ALL in imatinib era.</p><p><b>METHODS</b>Retrospectively analyzed 97 newly diagnosed adult Ph⁺ ALL patients from 2005 to 2013. According to whether administrated imatinib in the induction therapy and the administrating duration (≥3 d) , they were divided into imatinib (n=37) and non-imatinib group (n=60), and the former group was further divided into early-use (n=26) and late-use imatinib groups (n=11) (bounded by the fourteenth day of induction chemotherapy). We compared the overall response rate (ORR) and the negative rate of BCR-ABL fusion gene in patients who achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) among the three groups at the end of the first induction therapy. There were 44 cases underwent allo-HSCT (transplant group) and 33 cases only adopted imatinib-based chemotherapy (non-transplant group) in 77 patients who administrated imatinib as a maintenance therapy, we further compared the incidences of overall survival (OS) , disease-free survival (DFS), relapse and nonrelapse mortality (NRM) between the two groups; and dynamically monitor polymerase chain reaction (PCR) negativity of patients who were in CR1 state before transplant (n=34) at the following timepoints of achieving CR or CRi, the first consolidation therapy, beginning the pretreatment of transplant and attaining hematopoietic reconstruction after transplant.</p><p><b>RESULTS</b>After the first induction therapy, the ORR of imatinib group was significantly higher than of non-imatinib group (97.3%, 72.9% respectively, P=0.002), but early-use and late-use imatinib groups had no statistical significance in ORR (100% , 90.9% respectively, P=0.297); the rate of negativity of imatinib and non- imatinib groups were 20.0% and 0 respectively (P=0.041) in patients who achieved CR or CRi. The negative rate of patients in CR1 state before transplant attained 20.8%, 42.3%, 51.8%, 76.8%, respectively at the previously described 4 timepoints. And the differences between the fourth and the third, the third and the first timepiont all reached statistical significance (P=0.044, 0.022, respectively). The 5-year OS of transplant and non- transplant groups showed statistical difference (47.0%, 28.0% respectively, P=0.016), also for 5-year DFS (P=0.001) and the cumulative rate of relapse (P=0.000) of the former surpassing the latter; the cumulative rate of NRM between these two groups had no statistical significance (P=0.370).</p><p><b>CONCLUSION</b>Conventional induction chemotherapy in combination with imatinib in the first induction therapy of adult Ph⁺ ALL, not only improved the rate of hematologic remission, also the rate of molecular response. Imatinib used as a consolidation and maintenance therapy after remission, and allo-HSCT scheduled as soon as possible improved the prognosis.</p>
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Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Benzamides , Therapeutic Uses , Disease-Free Survival , Hematopoietic Stem Cell Transplantation , Imatinib Mesylate , Philadelphia Chromosome , Piperazines , Therapeutic Uses , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Therapeutics , Protein Kinase Inhibitors , Therapeutic Uses , Pyrimidines , Therapeutic Uses , Retrospective Studies , Transplantation, Homologous , Treatment OutcomeABSTRACT
Viral infections remain the common cause of morbidity and mortality in immunocompromised patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).Virus antigens can be recognized by cytotoxic T-lymphocytes (CTL) in the context of HLA class Ⅰ molecules.T-cell-based immunotherapies are now being included in the clinical practice of transplant recipients to prevent and treat viral infections and complications associated with CMV,AdV and EBV.Here,the current status and future feasibility of CTL immunotherapy for virus infections after allo-HSCT are discussed.
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ObjcetiveTo study the chimerism status ot bone marrow mesenchymal stem cells (BMSC) following double-unit cord blood stem cell transplantation (DCBT).MethodsBone marrow mononuclear cells were isolated by ficoll density gradient centrifugation from the patient following DCBT and healthy donors.After cultured for about 20 days,BMSC surface makers,the ability to differentiate into adipocytes and osteoblast and the expression of hematopoietic and immune molecules were detected,moreover,chimerism status of BMSC were also evaluated by STR-PCR.ResultsMSC derived from the patient were similar to normal adult BMSC in morphology,surface and differentiation ability.Besides,MSC from the patient can express a variety of hematopoietic and immune molecules normally.The results of STR-PCR showed that the patient demonstrated complete donor chimerism,hematopoiesis in BM and PB were from a single unit cord blood (donor chimerism was 96.4％ and 95.7％,respectively).But the predominant cord blood chimerism of BMSC was 5.4％,the remaining part was from the patient himself.ConclusionSustained hematopoiesis was derived from a single unit cord blood following DCBT.The majority of BMSC were origin from host tissue,mixed chimerism donor part of MSC stemed from the engrafted unit of cord blood.
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The prevalence of allergy diseases is increasing globally. Epidemiological surveies showed that the increased allergy prevalence rates followed the time trend of rickets prophylaxis in western countries. and vitamin D supplement increased the risk of allergy in early stage.Currently,most of investigators think that vltamin D deficiency may be one of the risk factors for allergy diseases.Laboratory investigations showed that vitamin D inhibited Th1、dendritic cell(DC)and Th2 cell proliferating,and keeped on epithelial suIfaces barrier tunction.However,no study has found generating of allergy disease is associated with vitamin D deftciency or excess.
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Objective To investigate the correlation between the CD40 gene( - 1 C/T)single nucleotide polymorphism(SNP) and acute coronary syndromes(ACS), and the expression of CD40 on platelets. Method A total of 562 patients with ACS canfirmed by coronary angiography were divided into 3 groups according to the clinical characteristics, namely ACS patients( n = 210), stable angina(SA) patients( n = 189) and control group( n = 163).ACS was defined as ischemic chest pain at rest resulting in admission to hospital and > 50% stenosis in a major coronary artery with or without a rise in troponin Ⅰ. SA was defined as stable effort-related angina without change in angina pattern in 3 months. Patients with infection, tumor, or liver or kidney disease were excluded The gene polymorphism was measured by the polymerase chain reaction and restriction fragment length polymorphism(PCR-RFIP) and identiffed by sequencing. The expression of CD40 on platelets was detected by flow cytometry. The frequency, distribution of genotypes was compared using cross-tabulation and standard X~2 test. Result The CC genotype(31% ) and C allele of frequency(57.9%)of CD40 gene in ACS patients were significantly higher than those in SA(15.9%, 43.1% ) and control groups( 16.1%, 42.6% ). No significant difference of the genotypes or allele frequencies was found between SA and control group(X~2 = 0.053, P = 0.974;X~2 = 0.017, P = 0.897). 1he expression of CD40 on platelets in patients with C alleles carries was significandy higher than that of T allele carries in each group( P <0.0001). Conclusions CD40- 1C/T polymorphism was associated with ACS in Chinese Han nationallity.
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Objective To explore the characteristics of deficit in action imitation upon objects for the children with autistic spectrum disorder(ASD). Methods Imitative tasks involved objects under the condition of different time after the modelling action ,different action number, different action meaning were used to examine the variations between 12 young children with ASD,and with deaf children(D) matched with the non-verbal IQ and CA( n= 12) ,and children with mental retardation (MR) matched with verbal IQ and CA( n= 12). Results Analyses of repeated ANOVA revealed that: there were significant main effect on the imitation of action involved objects within three subjects(F(2.33) = 10. 138, P＜0.01 ) ;the individuals with ASD achieved lower scores(0.766 ±0.029 ) than the children with MR (0.861 ± 0. 029 ), and the children with deaf significantly ( 0. 949 ± 0. 029). Especially,the autistic imitation deficit was shown on tasks of deferred and meaningless action imitation. Conclusion Children with ASD show deficit on imitation involved objects significantly.