Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcran...Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcranial magnetic simulation on changes in several nonlinear dynamic electroenceph-alographic parameters in rats with chronic epilepsy and explored the mechanism underlying repeti-tive transcranial magnetic simulation-induced antiepileptic effects. An epilepsy model was estab-lished using lithium-pilocarpine intraperitoneal injection into adult Sprague-Dawley rats, which were then treated with repetitive transcranial magnetic simulation for 7 consecutive days. Nonlinear elec-electroencephalographic parameters were obtained from the rats at 7, 14, and 28 days post-stimulation. Results showed significantly lower mean correlation-dimension and Kolmogo-rov-entropy values for stimulated rats than for non-stimulated rats. At 28 days, the complexity and point-wise correlation dimensional values were lower in stimulated rats. Low-frequency repetitive transcranial magnetic simulation has suppressive effects on electrical activity in epileptic rats, thus explaining its effectiveness in treating epilepsy.展开更多
BAOKGROUND： Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation ...BAOKGROUND： Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation （rTMS） involves an anti-apoptotic effect via regulating Bcl-2 and Fas protein expression remains to be determined. OBJECTIVE： To verify the correlation between the anti-epileptic mechanism following pretreatment of low-frequency rTMS and anti-hippocampal apoptosis. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at Institute of Neurological Disorders, Affiliated Hospital of North Sichuan Medical College between September 2007 and March 2008. MATERIALS： Pilocarpine （053K13011） was provided by Sigma, USA; lithium was provided by Shanghai Biotechnology Co., Ltd., China; Dantec Maglite-r25 rTMS instrument was provided by Dundee, Denmark. METHODS： A total of 21 adult male Wistar rats were randomly divided into control （n = 6）, rTMS pretreatment （n = 9）, and sham-stimulation （n = 6） groups. The rTMS pretreatment group was pretreated with low-frequency rTMS （0.5 Hz, 75% threshold intensity, 20 times/bundle, and 5 bundles/day）, while the sham-stimulation group was sham-stimulated with a similar sound for 7 successive days to establish lithium-pilocarpine-induced epileptic state models. MAIN OUTCOME MEASURES： Epileptic stroke latency; neuronal morphology was observed using hematoxylin and eosin staining; mean positive-reactive cell number and mean absorbance of Bcl-2 and Fas protein in the hippocampal CA1 region was observed using immunohistochemistry. RESULTS： Epileptic latency in the rTMS pretreatment group was significantly enhanced （P 〈 0.01）, and a number of degenerated neurons were observed to be apoptotic. Bcl-2 protein expression increased at each time point, but Fas protein expression decreased （P 〈 0.01）. CONCLUSION： Low-frequency rTMS has an anti-epileptic effect, which may be via regulation of Bcl-2 and Fas protein expression in the hippocampal region.展开更多
Objective To develop a novel prognostic scoring system for severe cytokine release syndrome(CRS)in patients with B-cell acute lymphoblastic leukemia(B-ALL)treated with anti-CD19 chimeric antigen receptor(CAR)-T-cell t...Objective To develop a novel prognostic scoring system for severe cytokine release syndrome(CRS)in patients with B-cell acute lymphoblastic leukemia(B-ALL)treated with anti-CD19 chimeric antigen receptor(CAR)-T-cell therapy,aiming to optimize risk mitigation strategies and improve clinical management.Methods This single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023.These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data,documented CRS grading,and at least 3 months of follow-up.Data on patient demographics,treatment history,laboratory parameters,CAR-T-cell characteristics,safety,and efficacy endpoints were collected.CRS severity was graded according to the 2019 ASTCT consensus criteria.Univariate and multivariate logistic regression analyses were conducted to identify factors associated with CRS severity,and a prognostic model was constructed.Results The overall incidence of CRS was 67.2%,with 13.6%having grade≥3(severe)CRS.Higher baseline and post-lymphodepletion minimal residual disease(MRD)levels and neutropenia on day 7 post-infusion were significantly associated with severe CRS.Inflammatory markers(CRP,ferritin,and IL-6)and coagulation dysfunction(APTT)on day 7 post-infusion were also predictive of CRS severity.The prognostic model incorporating these factors demonstrated robust discriminatory ability,with an area under the ROC curve of 0.875.Conclusion This study developed a novel prognostic scoring system for severe CRS in Chinese B-ALL patients receiving anti-CD19 CAR-T-cell therapy.The model integrates clinical and laboratory parameters to facilitate early identification and management of severe CRS.Further validation in larger,prospective cohorts is warranted.展开更多
基金supported by the Key Project of Sichuan Provincial Education Department,No.(2010)597
文摘Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcranial magnetic simulation on changes in several nonlinear dynamic electroenceph-alographic parameters in rats with chronic epilepsy and explored the mechanism underlying repeti-tive transcranial magnetic simulation-induced antiepileptic effects. An epilepsy model was estab-lished using lithium-pilocarpine intraperitoneal injection into adult Sprague-Dawley rats, which were then treated with repetitive transcranial magnetic simulation for 7 consecutive days. Nonlinear elec-electroencephalographic parameters were obtained from the rats at 7, 14, and 28 days post-stimulation. Results showed significantly lower mean correlation-dimension and Kolmogo-rov-entropy values for stimulated rats than for non-stimulated rats. At 28 days, the complexity and point-wise correlation dimensional values were lower in stimulated rats. Low-frequency repetitive transcranial magnetic simulation has suppressive effects on electrical activity in epileptic rats, thus explaining its effectiveness in treating epilepsy.
基金Youth Foundation Project of Sichuan Province, No. 04ZQ026-010
文摘BAOKGROUND： Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation （rTMS） involves an anti-apoptotic effect via regulating Bcl-2 and Fas protein expression remains to be determined. OBJECTIVE： To verify the correlation between the anti-epileptic mechanism following pretreatment of low-frequency rTMS and anti-hippocampal apoptosis. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at Institute of Neurological Disorders, Affiliated Hospital of North Sichuan Medical College between September 2007 and March 2008. MATERIALS： Pilocarpine （053K13011） was provided by Sigma, USA; lithium was provided by Shanghai Biotechnology Co., Ltd., China; Dantec Maglite-r25 rTMS instrument was provided by Dundee, Denmark. METHODS： A total of 21 adult male Wistar rats were randomly divided into control （n = 6）, rTMS pretreatment （n = 9）, and sham-stimulation （n = 6） groups. The rTMS pretreatment group was pretreated with low-frequency rTMS （0.5 Hz, 75% threshold intensity, 20 times/bundle, and 5 bundles/day）, while the sham-stimulation group was sham-stimulated with a similar sound for 7 successive days to establish lithium-pilocarpine-induced epileptic state models. MAIN OUTCOME MEASURES： Epileptic stroke latency; neuronal morphology was observed using hematoxylin and eosin staining; mean positive-reactive cell number and mean absorbance of Bcl-2 and Fas protein in the hippocampal CA1 region was observed using immunohistochemistry. RESULTS： Epileptic latency in the rTMS pretreatment group was significantly enhanced （P 〈 0.01）, and a number of degenerated neurons were observed to be apoptotic. Bcl-2 protein expression increased at each time point, but Fas protein expression decreased （P 〈 0.01）. CONCLUSION： Low-frequency rTMS has an anti-epileptic effect, which may be via regulation of Bcl-2 and Fas protein expression in the hippocampal region.
基金supported by grants from the National Natural Science Foundation of China(No.82400212).
文摘Objective To develop a novel prognostic scoring system for severe cytokine release syndrome(CRS)in patients with B-cell acute lymphoblastic leukemia(B-ALL)treated with anti-CD19 chimeric antigen receptor(CAR)-T-cell therapy,aiming to optimize risk mitigation strategies and improve clinical management.Methods This single-center retrospective cohort study included 125 B-ALL patients who received anti-CD19 CAR-T-cell therapy from January 2017 to October 2023.These cases were selected from a cohort of over 500 treated patients on the basis of the availability of comprehensive baseline data,documented CRS grading,and at least 3 months of follow-up.Data on patient demographics,treatment history,laboratory parameters,CAR-T-cell characteristics,safety,and efficacy endpoints were collected.CRS severity was graded according to the 2019 ASTCT consensus criteria.Univariate and multivariate logistic regression analyses were conducted to identify factors associated with CRS severity,and a prognostic model was constructed.Results The overall incidence of CRS was 67.2%,with 13.6%having grade≥3(severe)CRS.Higher baseline and post-lymphodepletion minimal residual disease(MRD)levels and neutropenia on day 7 post-infusion were significantly associated with severe CRS.Inflammatory markers(CRP,ferritin,and IL-6)and coagulation dysfunction(APTT)on day 7 post-infusion were also predictive of CRS severity.The prognostic model incorporating these factors demonstrated robust discriminatory ability,with an area under the ROC curve of 0.875.Conclusion This study developed a novel prognostic scoring system for severe CRS in Chinese B-ALL patients receiving anti-CD19 CAR-T-cell therapy.The model integrates clinical and laboratory parameters to facilitate early identification and management of severe CRS.Further validation in larger,prospective cohorts is warranted.
