Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Aim To investigate the effect and role of neuronal restriction silencing factor(REST/NRSF)in epilepsy disorder.Methods Immunohistochemistry,immunofluorescence,Western blot and qPCR tech-niques were used to detect REST/NRSF expression levels in hippocampal tissues of mice induced by kainic acid and human brain tissue.Viral injections,EEG re-cordings and behavioral methods were used to test the effects on epileptic mice after knockdown and overex-pression of REST/NRSF in the hippocampal CA1 re-gion,respectively.Results The positive rate of REST/NRSF in the lesions of epileptic patients was significantly higher compared with that in the control group.The levels of REST/NRSF protein and mRNA in the CA1 region of the hippocampus of mice in the KA model group were significantly higher.Kv7.2 and Kv7.3 potassium channel mRNA expression levels were significantly down-regulated.Significant up-regu-lation of REST/NRSF expression levels was observed in mouse hippocampus after NMDA injection.Knock-down of REST/NRSF in the CA1 region of hippocam-pus significantly elevated the expression levels of Kv7.2 and Kv7.3 potassium channel mRNAs.The fre-quency of EEG spiking and sharp-wave issuance and epileptic seizure grade were significantly lower.Over-expression of REST/NRSF in the CA1 region of hippo-campus significantly reduced the mRNA expression lev-els of Kv7.2 and Kv7.3 potassium channels.The fre-quency of EEG spiking and sharp-wave issuance was significantly higher and epileptic symptoms were exac-erbated.Conclusion REST/NRSF in mouse hipp-ocampal brain regions is involved in epileptic disease development through transcriptional regulation of Kv7.2 and Kv7.3 potassium channels.

Flavonoids are a class of compounds with a variety of biological activities widely found in nature,mainly including an-tioxidant,anti-inflammatory,antibacterial,anti-tumor,anti-al-lergic,hypoglycemic,cardiovascular protection and other phar-macological effects.In recent years,the anti-neuroinflammatory effects of flavonoids have received widespread attention,and studies have found that they can improve neuroinflammation and exert neuroprotective effects through multiple pathways and chan-nels.Neuroinflammation,as one of the important etiological and predisposing factors of neurodegenerative diseases,suppression of neuroinflammation is considered an important tool for the pre-vention and treatment of neurodegenerative diseases.This paper reviews the relationship between neuroinflammation and neurode-generative diseases,and summarizes the possible mechanisms of action of flavonoids intervening in neuroinflammation to treat neurodegenerative diseases,with a view to providing references for further basic research on flavonoid components and new re-search ideas and methods for the development of drugs for the treatment of neurodegenerative diseases.

Objective:To determine divalent mercury,methylmercury and ethylmercury in Huoxue Zhitong capsules,and to provide data support for the risk assessment and management of traditional medicines products.Methods:High performance liquid chromatography-hydrogenation-atomic fluorescence spectrometry(HPLC-HG-AFS)was used to determine the content of three forms of mercury(divalent mercury,Hg2+;methyl mercury,CH3 Hg;ethyl mercury,C2H5Hg)in different batches of Huoxue Zhitong capsules.Chromatographic conditions were C18 column(250 mm ×4.6 mm,5 μ·m)and acetonitrile-0.06 mol·L-1 ammonium acetate solution(containing 0.01 mol·L-1 L-cysteine)(5∶95)as a mobile phase.Hydride generation parameters were oxidant agent of 1％potassium persulfate-0.35％potassium hydroxide mixed solution,reducing agent of 2.0％potassium borohydride-0.35％potassium hydroxide mixed solution,carrier solution of 7％hydrochloric acid,negative high pressure of 285 V,and atomizer height of 10 mm.Results:The linear range of mercury species was 1.00-10.0 μg·L-1 with r＞0.999.The detection limit values were 0.088-0.131 ng·L-1,and the average recoveries ranged from 91.98％to 93.10％with RSD of＜5.73％(n=3).Three mercury forms in different batches of Huoxue Zhitong capsules by HPLC-HG-AFS were below the detection limits.Conclusion:The validated method can be used for the determination of mercury speciation in Huoxue Zhitong capsules and other Chinese patent medicines,which pro-vides a reference for the safety assessment of Chinese patent medicines.

In recent years,studies have shown that C/EBP β plays an important role in the occurrence and development of liver cancer,but its specific molecular regulatory mechanism is still unclear.In this study,we analyzed the GEO database and the Kaplan-Meier Plotter database and found that the mRNA expression of C/EBP β was low in hepatocellular carcinoma(HCC)cells(P＜0.05),and its low ex-pression was closely related to the prognosis of HCC patients.Furthermore,functional enrichment analy-sis and TIMER database analysis showed that C/EBP β was mainly involved in biological processes such as cell cycle and DNA transcription,and the expression level of C/EBP β had a strong correlation with the immune infiltration of CD4+T cells and macrophages(P＜0.05).To further investigate the effect of C/EBP β on the proliferation and migration of HCC cells.In the experiment,HCC cells were transiently transfected with C/EBP β siRNA and divided into si-NC group and siC/EBP β group.The mRNA and protein levels of C/EBP β in HCC cells were significantly reduced by qRT-PCR and Western blot(P＜0.05),and MTT detection,plate cloning assay,and 5-ethynyl-2'deoxyuracil nucleoside(Edu)assay confirmed that knockdown of C/EBP β promotes the proliferation of HCC cells(P＜0.05);Transwell and scratch assays confirmed that knockdown of C/EBP β promote the migration of HCC cells;Western blot method was used to detect the effect of knockdown of C/EBP β on the expression of migration-related proteins(E-cadherin,N-cadherin)and Wnt/β-catenin signaling pathway proteins.The results showed that knockdown of C/EBP β promotes epithelial-mesenchymal transition(EMT)and activates gene ex-pression of Wnt/β-catenin signaling pathway in HCC cells(P＜0.05).In conclusion,C/EBP β was un-derexpressed in HCC tissues and was positively correlated with the survival prognosis of patients.Knock-down of C/EBP β may promote the proliferation,migration,and epithelial-mesenchymal transformation of HCC cells by activating the Wnt/β-catenin signaling pathway,which provides a basis for the role of C/EBP β in the occurrence and development of HCC and may be a potential target in the diagnosis and treatment of HCC.

Objective:To investigate the correlation of miR-155 expression with drug sensitivity of FLT3-ITD+acute myeloid leukemia(AML)cell line and its potential regulatory mechanism.Methods:By knocking out miR-155 gene in FLT3-ITD+AML cell line MV411 through CRISPR/Cas9 gene-editing technology,monoclonal cells were screened.The genotype of these monoclonal cells was validated by PCR and Sanger sequencing.The expression of mature miRNA was measured by RT-qPCR.The treatment response of doxorubicin,quizartinib and midostaurin were measured by MTT assay and IC50 of these drugs were calculated to identify the sensitivity.Transcriptome sequencing was used to analyze change of mRNA level in MV411 cells after miR-155 knockout,gene set enrichment analysis to analyze change of signaling pathway,and Western blot to verify expressions of key molecules in signaling pathway.Results:Four heterozygotes with gene knockout and one heterozygote with gene insertion were obtained through PCR screening and Sanger sequencing.RT-qPCR results showed that the expression of mature miR-155 in the monoclonal cells was significantly lower than wild-type clones.MTT results showed that the sensitivity of MV411 cells to various anti FLT3-ITD+AML drugs increased significantly after miR-155 knockout compared with wild-type clones.RNA sequencing showed that the mTOR signaling pathway and Wnt signaling pathway were inhibited after miR-155 knockout.Western blot showed that the expressions of key molecules p-mTOR,Wnt5α and β-catenin in signaling pathway were down-regulated.Conclusion:Drug sensitivity of MV411 cells to doxorubicin,quizartinib and midostaurin can be enhanced significantly after miR-155 knockout,which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.

Objective:To screen interleukin(IL)-1β secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice.Methods:THP-1 cell line was differentiated to obtain human THP-1-derived macrophages,and the primary macrophages were obtained from human peripheral blood.FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice.The macrophages in abdominal cavity and bone marrow of mice were cultivated.The cells were treated with ABCC1/MRP1,ABCG2/BCRP,ABCB1/P-gp,OATP1B1,and MATE transporter inhibitors,then stimulated by lipopolysaccharide and adenosine triphosphate.The secretion level of IL-iβ was detected by ELISA,Western blot,and immunofluorescence.Results:After inhibiting ABCC1/MRP1 transporter,the secretion of IL-1β decreased significantly,while inhibition of the other 4 transporters had no effect.In animal experiment,the level of IL-1 β secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group(P＜0.05).Conclusion:ABCC1/MRP1 transporter is a newly discovered IL-1β secretion pathway,which is expected to become a new target for solving clinical problems such as cytokine release syndrome.

Objective:To investigate the correlation of the clinical characteristics,fever characteristics,serum biomarkers with cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma (R/R MM) treated with chimeric antigen receptor T cell (CAR-T) immunotherapy. Methods:104 R/R MM patients who received CAR-T cell therapy at the Affiliated Hospital of Xuzhou Medical University from June 2017 to November 2021 were included,and the correlations of their clinical characteristics,fever characteristics,serum biomarkers with the severity of CRS were analyzed. Results:Among 104 R/R MM patients receiving CAR-T treatment,no CRS was observed in 8 cases (7.7％),and 96 cases (92.3％) developed CRS. Patients with high-risk cytogenetics had a higher risk of developing CRS (P=0.040),while patients who had previously received autologous hematopoietic stem cell transplantation (ASCT) had a lower risk of developing CRS (P=0.004). There was a significant difference in the duration of fever between patients with grade 1-2 and grade 3-5 CRS (P=0.006). The highest body temperature varied among patients with different treatment regimens (P=0.001). The decrease in total protein in patients with CRS was more significant than in patients without CRS (P=0.002). Within one month after CAR-T cell infusion,the degree of albumin recovery in patients with grade 3-5 CRS was lower than that in patients with grade 0-2 CRS (P=0.037). Compared to patients with grade 1-2 CRS,patients with grade 3-5 CRS showed a significant increase in heart rate after CAR-T cell infusion (P=0.013),while IL-6,C-reactive protein (CRP),and serum ferritin (SF) also showed significant increases (P=0.007,P<0.001,P=0.003). Conclusion:High-risk cytogenetics is a risk factor for severe CRS. Long duration of fever is a clinical characteristic of severe CRS. CRP can better reflect the severity of CRS.