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.

Objective To study the change of lipidomics in chronic cadmium-exposed mice,thereby screening out lipid subclasses,lipid molecules and enriched metabolic pathways with significant differences.Methods Twelve SPF male C57BL/6J mice(8 weeks old)were randomly divided into the control group(normal water feeding)and the experimental group[cadmium water(0.6 mg/L of CdCl2)feeding],with 6 mice in each group.Mice were sacrificed after 6 months of cadmium exposure,and fresh liver tissues were collected immediately.Lipid oil red O staining and lipidomics analysis were performed on liver tissue.Results Compared with the control group,the liver tissue of mice in the experimental group did not appear red after lipid oil red O staining.Seventeen lipid subclasses with significant differences and 144 lipid molecules with significant differences were screened out by lipidomics.These lipid molecules with significant differences were enriched in glycerophospholipid metabolism,linoleic acid metabolism,alpha-linolenic acid metabolism,glycosylphosphati-dylinositol biosynthesis,glycerolipid metabolism and arachidonic acid metabolism by KEGG.Conclusion This study reveals that chronic cadmium exposure can induce the disorder of lipid subclasses and lipid metabolites in the liver of mice,which provides a basis for understanding the non-alcoholic fatty liver disease caused by chronic cadmium exposure.

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

[Abstract] Objective: To investigate the mechanisms of carnitine palmitoyltransferase 1c (CPT1c) expression to affect the proliferation and apoptosis of human thyroid papillary cancer B-CPAP cells through the AMP-dependent/activated protein kinase (AMPK) pathway in the low glucose and hypoxic conditions. Methods: Firstly,humanthyroidpapillarycarcinomaB-CPAP cells were cultured under normal condition or low glucose and hypoxic condition respectively, followed with the treatment of AMPK inhibitor compound C. Western blotting was used to detect the expressions of AMPK, p-AMPK, peroxisome proliferator-activated receptor α (PPARα) and CPT1c; the proliferation and apoptosis were detected by CCK-8 and Flow cytometry, respectively. Then PPARα-siRNA was synthesized and transfected into B-CPAP cells to knock down PPARα, and then the cells were cultured under normal or low glucose and hypoxic condition respectively.Above indicators were also detected to verify the regulation of PPARα on CPT1c. Finally, the human luciferase reporter plasmid containing CPT1c gene promoter was constructed, and the effect of PPARα on the activity of CPT1c promoter luciferase activity was observed by immunofluorescence. Results: The expressions ofAMPK, p-AMPK, PPARα and CPT1c were significantly increased in B-CPAP cells under low glucose and hypoxia condition (P<0.05 or P<0.01), while cell proliferation and apoptosis rate did not change significantly (P>0.05). After the treatment of AMPK inhibitor compound C, the expressions of p-AMPK, PPARα and CPT1c in low glucose and hypoxia group were significantly decreased (P<0.05 or P<0.01), the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). However, the change range was smaller than that in the normal culture + compound C group (P<0.05).After PPARα knockdown, the expressions ofAMPK, p-AMPK, PPARα and CPT1c in cancer cells cultured under normal conditions were significantly decreased (P<0.05 or P<0.01), and the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). While under low glucose and hypoxia condition, the expression of CPT1c in cells after transfection was significantly decreased (P<0.05), and the inhibition rate on cell proliferation and the apoptosis rate were significantly increased (P<0.05); However, the change range was still lower than that of normal condition group after transfection (P<0.05).After PPARα overexpression, the ratio of fluorescence in the empty vector group was not significantly different from that of the blank group (P>0.05), and the ratio of fluorescence was significantly increased in PPARα over-expression group (P<0.05). Conclusions: AMPK can increase the expression of PPARα to promote the expression of CPT1c in thyroid cancer B-CPAP cells under low glucose and hypoxia conditions, thereby inhibiting cell apoptosis and maintaining cell proliferation ability.