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The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy.
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MicroRNAs , Traumatismos da Medula Espinal , Animais , Necroptose/genética , Biologia Computacional , Perfilação da Expressão Gênica , MicroRNAs/genética , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/genéticaRESUMO
The persistence or recurrence of minimal residual disease (MRD) after chemotherapy predicts relapse of B-cell acute lymphoblastic leukemia (B-ALL). CD19-directed chimeric antigen receptor T (CD19 CAR-T) cells have shown promising responses in B-ALL. However, their role in chemotherapy-refractory MRD-positive B-ALL remains unclear. Here we aimed to assess the effectiveness and safety of CD19 CAR-T cells in MRD-positive B-ALL patients. From January 2018, a total of 14 MRD-positive B-ALL patients received one or more infusions of autogenous CD19 CAR-T cells. Among them, 12 patients achieved MRD-negative remission after one cycle of CAR-T infusion. At a median follow-up time of 647 days (range 172-945 days), the 2-year event-free survival rate in MRD-positive patients was 61.2% ± 14.0% and the 2-year overall survival was 78.6 ± 11.0%, which were significantly higher than patients with active disease (blasts ≥ 5% or with extramedullary disease). Moreover, patients with MRD had a lower grade of cytokine release syndrome (CRS) than patients with active disease. However, the peak expansion of CAR-T cells in MRD positive patients showed no statistical difference compared to patients with active disease. Five patients received two or more CAR-T cell infusions and these patients showed a decreased peak expansion of CAR-T cell in subsequent infusions. In conclusion, pre-emptive CD19 CAR-T cell treatment is an effective and safe approach and may confer sustained remission in B-ALL patients with chemotherapy-refractory MRD. The trials were registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).
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Antígenos CD19/imunologia , Linfoma de Células B/imunologia , Neoplasia Residual/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Imunoterapia Adotiva/métodos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Recidiva , Adulto JovemRESUMO
STAT5 is an important transcription factor that is constitutively activated in various types of malignancies, including chronic myelogenous leukemia (CML). Whether the antitumor effects of resveratrol (RES) are linked to its capability to inhibit STAT5 activation in CML cells was investigated. We found that RES inhibited STAT5 activation in K562 and KU812 cell lines; RES also reduced the STAT5 concentration in the nucleus of K562 and KU812 cells. Protein tyrosine phosphatase (PTP) inhibitor, sodium pervanadate, reversed the RES-induced downregulation of STAT5, suggesting the involvement of a PTP. Indeed, we observed that RES decreased the expression of tyrosine phosphatase SHP-1 and SHP-2; moreover, the deletion of SHP-1 and SHP-2 genes by siRNA abolished the ability of RES to inhibit STAT5 activation, which suggested the critical role of both SHP-1 and SHP-2 in its possible mechanism of action. RES downregulated the expression of STAT5-regulated gene products such as Bcl-xL, Bcl-2, Cyclin D1, and Mcl-1, and increased the expression of Bax. This correlated with the suppression of proliferation and induction of apoptosis. Overall, our results suggest that RES is a blocker of STAT5 activation and thus may be potentially useful for the treatment of CML.
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Antineoplásicos Fitogênicos/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteína Tirosina Fosfatase não Receptora Tipo 11/biossíntese , Proteína Tirosina Fosfatase não Receptora Tipo 6/biossíntese , Resveratrol/farmacologia , Fator de Transcrição STAT5/antagonistas & inibidores , Proteínas Supressoras de Tumor/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Transdução de SinaisRESUMO
BACKGROUND/AIMS: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. METHODS: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. RESULTS: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-ß/Smad pathway, evidenced by no change in the expression of TGF-ß and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF-ß-induced fibrosis. CONCLUSIONS: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy.
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Proteína 1 de Resposta de Crescimento Precoce/genética , Espaço Epidural/efeitos dos fármacos , Espaço Epidural/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Taurina/uso terapêutico , Animais , Células Cultivadas , Regulação para Baixo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Espaço Epidural/citologia , Espaço Epidural/metabolismo , Fibrose , Laminectomia , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND/AIMS: Hypertrophic scars (HS) formation results from reduced apoptosis and increased proliferation of fibroblasts. Therefore, apoptosis of fibroblasts is a key target for the development of novel therapeutic strategies for HS. Previous reports demonstrated that FK506 could attenuate scar formation in vivo and FK506 could also induce endoplasmic reticulum stress (ER stress). However, the effects of FK506 on ER stress-mediated apoptosis in fibroblasts remain unclear. METHODS: Rat skin fibroblasts were used in the study. Cell viability was examined using cell counting Kit-8. Apoptosis was detected by Annexin V/Propidium Iodide Double Staining. Gene silencing was performed using Small Interfering RNAs (siRNAs) or via lentiviral infection. The expression of apoptosis-related proteins was determined via Western blot. Interaction between proteins was explored by co-immunoprecipitation. RESULTS: FK506 significantly reduced cell viability and induced apoptosis in fibroblasts. Interestingly, ER stress was also activated after FK506 treatment. We further demonstrated that FK506-induced apoptosis was mediated by ER stress via activating CHOP, evidenced by decreased apoptosis after inhibition of ER stress using TUDCA or silencing expression of CHOP. Furthermore, Co-immunoprecipitation results indicated that treatment of FK506 induced disassociation of FKBP12.6 from RyR2 and its translocation from ER membrane to cytosol, consequently promoting ER stress-mediated apoptosis. CONCLUSION: FK506-induced fibroblasts apoptosis was mediated by ER stress via CHOP signaling pathway.
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Inibidores de Calcineurina/farmacologia , Estresse do Retículo Endoplasmático/genética , Fibroblastos/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Tacrolimo/farmacologia , Fator de Transcrição CHOP/genética , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Apoptose/genética , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Transdução de Sinais , Proteínas de Ligação a Tacrolimo/metabolismo , Fator de Transcrição CHOP/antagonistas & inibidores , Fator de Transcrição CHOP/metabolismoRESUMO
PURPOSE: To ascertain the anatomic and radiological parameters of the atlas (C1) pedicle and to explore a preferable method of C1 pedicle screw insertion. METHODS: Thirty-four conserved human cadaveric cervical spines (20 males, 14 females) underwent computed tomography (CT) scanning. Trajectories P (perpendicular to the coronal plane) and I (with medial inclination) were designed for each C1 pedicle on CT images. External pedicle wall width, medullary cavity width, transverse angle, and optimal entry point along each trajectory were measured. Cortical screws of 3.5 mm in diameter were inserted into C1 pedicles along trajectory P and I, respectively, and wall perforation was assessed (post-operative CT scanning). RESULTS: The external pedicle wall width and medullary cavity width along trajectory I were significantly wider than trajectory P (P < 0.01). Although external pedicle wall widths were all greater than 3.5 mm, medullary cavity width <3.5 mm was found in 16.1 % pedicles along trajectory P and only 2.9 % along trajectory I. Transverse angle was 21.8° along trajectory I and 0° along trajectory P. Optimal entry point of trajectory I was 4.1 mm lateral from that of trajectory P. The lateral wall perforation rate was significantly lower along trajectory I than trajectory P (P < 0.05). CONCLUSIONS: C1 pedicle screw trajectory with medial inclination and more lateral entry points yielded wider medullary cavity width than that perpendicular to the coronal plane, and might minimize lateral wall perforation.
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Atlas Cervical/diagnóstico por imagem , Parafusos Pediculares , Adulto , Cadáver , Atlas Cervical/anatomia & histologia , Atlas Cervical/cirurgia , Feminino , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of osteoporotic fracture. The bilateral pedicular approach is the most frequently used method. However, unilateral PVP is becoming increasingly more attractive for surgeons because of its numerous benefits, including lower radiation exposure, less tissue injury, and less bone cement leakage. The purpose of this study was to investigate the anatomical feasibility of unilateral PVP by exploring the differences in the puncture success rate of the unilateral pedicular approach among different lumbar segments, between men and women, and between the left and right sides. METHODS: Punctures were simulated on magnetic resonance imaging scans of 200 patients (100 men, 100 women) at a maximum angle via a pedicular approach. The distance between the entry point and the midline of the vertebral body, the maximum puncture angle, the puncture success value, and the puncture success rate were measured and compared among different lumbar levels, between the two sexes, and between the left and right sides. RESULTS: The maximum puncture distance between the entry point and the midline gradually increased from L1 to L5, and the maximum puncture angle showed the same tendency from L1 to L5. The puncture success values for L3 and L4 were higher than those for the other lumbar levels (L1, 31.53 ± 34.45; L2, 42.15 ± 28.06; L3, 56.21 ± 18.30; L4, 56.20 ± 12.93; and L5, 48.01 ± 6.88). The puncture success rates varied from 69.5 to 98.0 % among the different lumbar levels; L3 and L4 were the two highest (L3, 95.5 %; L4, 98.0 %). There were significant differences in these measurements between men and women and between the left and right sides. CONCLUSIONS: PVP with the unilateral puncture approach appears more likely to succeed at L3 to L5 than at L1 and L2. The unilateral approach might be more suitable for men than women at levels other than L5. Additionally, the left pedicular approach might be optimal for unilateral PVP procedures.
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Cimentos Ósseos/uso terapêutico , Vértebras Lombares/patologia , Imageamento por Ressonância Magnética , Fraturas por Osteoporose/patologia , Fraturas por Osteoporose/terapia , Fraturas da Coluna Vertebral/patologia , Fraturas da Coluna Vertebral/terapia , Vertebroplastia/métodos , Adolescente , Adulto , Idoso , Pontos de Referência Anatômicos , Estudos de Viabilidade , Feminino , Humanos , Injeções Espinhais , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Punções , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
A fluidized bed enrichment technique was developed to improve sensitivity of near infrared (NIR) spectroscopy with features of rapidness and large volume solution. D301 resin was used as an adsorption material to preconcentrate ß-naphthalenesulfonic acid in solutions in a concentration range of 2.0-100.0 µg/mL, and NIR spectra were measured directly relative to the ß-naphthalenesulfonic acid adsorbed on the material. An improved partial least squares (PLS) model was attained with the aid of multiplicative scatter correction pretreatment and stability competitive adaptive reweighted sampling wavenumber selection method. The root mean square error of cross validation was 1.87 µg/mL at PLS factor of 7. An independent test set was used to assess the model, with the relative error (RE) in an acceptable range of 0.46 to 10.03% and mean RE of 3.72%. This study confirmed the viability of the proposed method for the measurement of a low content of ß-naphthalenesulfonic acid in water.
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Naftalenossulfonatos/química , Espectroscopia de Luz Próxima ao Infravermelho , Poluentes Ambientais/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
OBJECTIVE: To screen the plasma microRNA (miRNA) profile of immune thrombocytopenia (ITP) patients. METHODS: Agilent 19.0 miRNA microarray was used to detect the expression profile of miRNA in plasma from 25 ITP patients and 20 healthy controls from June 2012 to September 2013. The software programs of TargetScan and miRanda were used for predicting target genes associated with differential miRNA. Then gene ontology (GO) and pathway analysis were performed to explore the genes and pathways involved in the pathogenesis of ITP. And differential miRNA was validated by real-time quantitative polymerase chain reaction (PCR). RESULTS: A genome-wide miRNA array revealed 29 differential miRNAs in the plasma samples of ITP patients including 15 up-regulated and 14 down-regulated miRNA. A total of 608 potential genes were predicted by TargetScan and miRanda.GO result showed that there were 475 (78.12%), 491(80.76%) and 533 (87.66%) genes respectively involved in biological process, molecular function and cellular component.Enrichment test showed 9 GO terms had significant difference (P < 0.05). Pathway analysis showed that 157 pathways were associated with 608 genes.Enrichment test showed 25 pathways had significant difference (P < 0.05). As revealed by real-time PCR, the expressions of miRNA4778-5p and miRNA4800-5p became obviously up-regulated while those of miRNA4707-5p, miRNA4721, miRNA3620-3p and miRNA378i decreased (all P < 0.05). The results agreed with those of microarray. CONCLUSIONS: The plasma differential miRNA profiles are identified in ITP patients. And miRNA is involved in calcium signaling pathway and T cell receptor signaling pathway may be associated with ITP pathogenesis.
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MicroRNAs/sangue , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/genética , Adulto , Estudos de Casos e Controles , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Púrpura Trombocitopênica Idiopática/etiologia , Transdução de Sinais/genéticaRESUMO
JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.
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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by autoantibody-mediated platelet destruction. Multiple factors have been implicated in ITP pathogenesis, including T-lymphocyte dysfunctions. The protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene encodes lymphoid-specific phosphatase (LYP), a critical negative regulator of T cell activation. Single nucleotide polymorphisms (SNPs) of PTPN22 have been broadly associated with susceptibilities to various autoimmune disorders. Here we conducted a case-control study investigating whether the PTPN22 -1123G > C SNP contributes to the risk of ITP in Chinese population. The study included 191 ITP cases and 216 ethnically matched normal controls. Genotyping of -1123G > C SNP was performed using a single-base extension (SBE) and mass spectrometry method. Allelic and genotypic frequencies were compared between the case-control groups by the chi-square test. We observed significant overrepresentation of -1123G allele (p = 0.034, odds ratio (OR) = 1.374, 95% confidence interval (CI) [1.024-1.843]) and GG genotype (P = 0.038, OR = 1.951, 95% CI [1.031-3.694]) in the patients compared with the controls. Stratified analysis by gender and age of disease onset revealed comparable observations in both male and adult ITP cohorts. These data suggest a moderate association of PTPN22 -1123G > C SNP with susceptibility to ITP. Together with previous reports, our finding provides further evidence for PTPN22 being a general autoimmunity gene.
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Povo Asiático/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Púrpura Trombocitopênica Idiopática/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Razão de Chances , Adulto JovemRESUMO
UNLABELLED: Idiopathic hypereosinophilic syndrome (HES) is a disease characterized by persistent hypereosinophilia (>1.5×109/L) for more than 6 months in the absence of other causes of reactive eosinophilia. Patients with HES presenting with multiorgan thromboses are rare. Herein we report a 57-year-old man with HES who presented with deep venous thrombosis of the lower extremities, portal thrombosis, pulmonary embolism, and mesenteric venous thrombosis, which led to intestinal obstruction. CONFLICT OF INTEREST: None declared.
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The current study aims to ascertain the anatomical feasibility of transferring the contralateral S1 ventral root (VR) to the ipsilateral L5 VR for treating unilateral spastic lower limb paralysis. Six formalin-fixed (three males and three females) cadavers were used. The VR of the contralateral S1 was transferred to the VR of the ipsilateral L5. The sural nerve was selected as a bridge between the donor and recipient nerve. The number of axons, the cross-sectional areas and the pertinent distances between the donor and recipient nerves were measured. The extradural S1 VR and L5 VR could be separated based on anatomical markers of the dorsal root ganglion. The gross distance between the S1 nerve root and L5 nerve root was 31.31 (± 3.23) mm in the six cadavers, while that on the diffusion tensor imaging was 47.51 (± 3.23) mm in 60 patients without spinal diseases, and both distances were seperately greater than that between the outlet of S1 from the spinal cord and the ganglion. The numbers of axons in the S1 VRs and L5 VRs were 13414.20 (± 2890.30) and 10613.20 (± 2135.58), respectively. The cross-sectional areas of the S1 VR and L5 VR were 1.68 (± 0.26) mm 2 and 1.08 (± 0.26) mm 2, respectively. In conclusion, transfer of the contralateral S1 VR to the ipsilateral L5 VR may be an anatomically feasible treatment option for unilateral spastic lower limb paralysis.
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Accurate discriminating nerve fibers is a prerequisite for right suturing nerves in nerve transfer operation. Various methods have been developed for identification of motor and sensory fibers, but no simple method meets the requirements in clinic. In this study, a surface-enhanced Raman scattering (SERS) lever strategy is designed and developed to detect Acetylcholinesterase (AchE) ultrasensitively, in which using produced thiocholine with weak intrinsic Raman activity (four ounces) to adjust absorbance of Rhodamine B with strong intrinsic Raman activity (thousand catties) on SERS-active substrates is to increase the sensitivity. Employing a miniaturized SERS substrate, SERS-active microneedles, is to decrease the volume of enzymolysis systems. Adopting an internal reference is to increase the repeatability of collected signal. The ultrasensitive AchE detection method discriminate samples with four times of difference in enzyme activity between 1-1 × 10-4 U/mL in about 10 min of enzymolysis time. AchE amounts in 2-mm-long segments of ventral and dorsal roots were about 0.00025-0.001 U and 0.01-0.02 U, respectively. The developed method would be a reliable method met the requirements of identifying motor and sensory fibers in clinic.
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Acetilcolinesterase , Análise Espectral Raman , Análise Espectral Raman/métodos , Tiocolina , Fibras NervosasRESUMO
OBJECTIVE: To explore the method of eliminating donor-specific anti-HLA antibodies (DSA) in haploidentical stem cell transplantation (haplo-SCT). METHODS: We present a refractory B-cell acute lymphoblastic leukemia (ALL) patient who had strongly positive DSA, but had no human leukocyte antigen-matched donor. Although CD38 expression on leukemia cells was negative, daratumumab combined with etoposide and venetoclax therapy was chosen for her. RESULTS: She achieved a significant decrease in DSA levels and complete remission on the combination therapy with daratumumab. She then received a haplo-SCT from a daughter as a donor and had a successful engraftment of donor stem cell. In haplo-SCT, strongly positive DSA levels, directed against donor HLA antigens, could be significantly reduced by daratumumab therapy before transplantation and successfully bridge subsequent haplo-SCT. CONCLUSION: Although CD38 expression is negative in leukemia cells, refractory B-ALL patients may still benefit from combination therapy with daratumumab. We need further clinical observation.
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Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Etoposídeo , Antígenos de Histocompatibilidade , Antígenos HLA , Indução de RemissãoRESUMO
STUDY DESIGN: Eight cadavers were included in this anatomical study. OBJECTIVE: This study aimed to confirm the anatomical feasibility of extradural transfer of the contralateral T11 ventral root (VR) to the ipsilateral L2 level and the contralateral L1 VR to the ipsilateral L3 level to restore lower limb function in cases of paraplegia. SUMMARY OF BACKGROUND DATA: Motor dysfunction due to hemiplegia significantly affects the daily life of patients. To date, unlike in cases of upper limb dysfunction, there are few studies on the surgical management of lower limb movement dysfunction. MATERIALS AND METHODS: Eight cadavers were included in this study to confirm the feasibility of the nerve transfer. After separating the VR and dorsal root at each level, the VRs at the T11 and L1 levels were anastomosed with the VRs of L2 and L3, respectively. The length of the VRs of donor roots and the distance between the donor and recipient nerves were measured. H&E staining was performed to verify the number of axons and the cross-sectional area of the VRs. Lumbar x-rays of 60 healthy adults were used to measure the distance between the donor and recipient nerves. RESULTS: After exposing the bilateral extradural each root, the VRs could be easily isolated from the whole root. The distance between the VRs of T11 and L2, L1, and L3 was significantly longer than the length of the donor nerve. Therefore, the sural nerve was used for grafting. The measurements performed on the lumbar x-rays of the 60 healthy adults confirmed the results. The number of axons and cross-sectional area of the VRs were measured. CONCLUSION: Our study confirmed the anatomical feasibility of transferring the VRs of T11 to L2 and that of L1 to L3 to restore lower limb function in cases of hemiplegia. LEVEL OF EVIDENCE: 5.
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Hemiplegia , Doenças Musculoesqueléticas , Adulto , Cadáver , Humanos , Extremidade Inferior/cirurgia , Paraplegia/cirurgia , Raízes Nervosas Espinhais/anatomia & histologia , Raízes Nervosas Espinhais/cirurgiaRESUMO
STUDY DESIGN: A total of 6 formalin-fixed cadavers were included in the cadaver feasibility study. OBJECTIVE: The aim was to ascertain the anatomical feasibility of extradural contralateral C7 ventral root transfer technique by cervical posterior. SUMMARY OF BACKGROUND DATA: Upper limb spastic hemiplegia is a common sequela after stroke. In our previous study, the authors established a method by transferring contralateral C7 dorsal and ventral roots to the corresponding C7 dorsal and ventral roots on the affected side in the cervical posterior. METHODS: In the present study, six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. Experimental anastomosis in cadavers was conducted. The pertinent lengths of the extradural nerve roots were measured. The tissue structures surrounding regions between the extradural CC7 nerve roots and the vertebral artery were observed. The cervical magnetic resonance imaging scans of 60 adults were used to measure the distance between the donor and recipient nerves. RESULTS: Experimental anastomosis showed that the distance between the donor and recipient nerves was approximately 1 cm; the short segment of the sural nerve needed bridging. The distance between both exit sites of the exit of the extradural dura mater was 33.57±1.55 mm. The length of the extradural CC7 ventral root was 22.00±0.98 mm. The ventral distance (vd) and the dorsal distance (dd) in males were 23.98±1.72 mm and 30.85±2.22 mm ( P <0.05), while those in females were 23.28±1.51 mm and 30.03±2.16 mm, respectively. C7 vertebral transverse process, ligaments, and other soft tissues were observed between the vertebral artery and the extradural C7 nerve root. CONCLUSION: Under the premise of less trauma, our study shows that the extradural contralateral C7 ventral root transfer technique, in theory, yields better surgical results, including better recovery of motor function and complete preservation of sensory function. LEVEL OF EVIDENCE: 5.
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Hemiplegia , Raízes Nervosas Espinhais , Adulto , Cadáver , Estudos de Viabilidade , Feminino , Formaldeído , Hemiplegia/cirurgia , Humanos , Masculino , Raízes Nervosas Espinhais/cirurgia , Extremidade SuperiorRESUMO
The recovery of lower-urinary-tract activity is a top priority for patients with spinal-cord injury. Historically, locomotor training improved micturition function in both patients with spinal cord injury and animal models. We explore whether training augments such as the supraspinal control of the external urethral sphincter results in enhanced coordination in detrusor-sphincter activity. We implemented a clinically relevant contusive spinal-cord injury at the 12th thoracic level in rats and administered forced wheel running exercise for 11 weeks. Awake rats then underwent bladder cystometrogram and sphincter electromyography recordings to examine the micturition reflex. Subsequently, pseudorabies-virus-encoding red fluorescent protein was injected into the sphincter to trans-synaptically trace the supraspinal innervation of Onuf's motoneurons. Training in the injury group reduced the occurrence of bladder nonvoiding contractions, decreased the voiding threshold and peak intravesical pressure, and shortened the latency of sphincter bursting during voiding, leading to enhanced voiding efficiency. Histological analysis demonstrated that the training increased the extent of spared spinal-cord tissue around the epicenter of lesions. Compared to the group of injury without exercise, training elicited denser 5-hydroxytryptamine-positive axon terminals in the vicinity of Onuf's motoneurons in the cord; more pseudorabies virus-labeled or c-fos expressing neurons were detected in the brainstem, suggesting the enhanced supraspinal control of sphincter activity. Thus, locomotor training promotes tissue sparing and axon innervation of spinal motoneurons to improve voiding function following contusive spinal-cord injury.
Assuntos
Contusões , Traumatismos da Medula Espinal , Animais , Humanos , Atividade Motora , Ratos , Traumatismos da Medula Espinal/patologia , Uretra/inervação , Uretra/fisiologia , Bexiga Urinária , Micção/fisiologiaRESUMO
Osteoporotic vertebral compression fracture (OVCF) has become a major public health issue that becomes more pressing with increasing global aging. Percutaneous kyphoplasty (PKP) is an effective treatment for OVCF. Robot-assisted PKP has been utilized in recent years to improve accuracy and reduce complications. However, the effectiveness of robot-assisted PKP in the treatment of multi-segmental OVCF has yet to be proved. This study was designed to compare the efficacy of robot-assisted and conventional fluoroscopy-assisted multi-segmental PKP. A total of 30 cases with multi-segmental OVCF between April 2019 and April 2021 were included in this study. Fifteen cases were assigned to the robot-assisted PKP group (robot group) and 15 cases to the conventional fluoroscopy-assisted PKP group (conventional fluoroscopy group). The number of fluoroscopic exposures, fluoroscopic dose, operation time, cement leakage rate, visual analog scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebral body (HFV) were compared between the 2 groups. The number of fluoroscopic exposures, fluoroscopic doses, and cement leakage rates in the robot group were lower than in the conventional fluoroscopy group ( P<0.05) while the operative time in the robot group was longer than in the conventional fluoroscopy group ( P<0.05). VAS score and VKA were decreased and HFV was increased after surgery in both groups ( P<0.05). Therefore, robot-assisted PKP for the treatment of multi-segmental OVCF can reduce the number of fluoroscopic exposures, fluoroscopic doses, and cement leakage compared to conventional treatment. As such, robot-assisted PKP has good application prospects and is potentially more effective in the treatment of multi-segmental OVCF.
RESUMO
Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.