Objective To investigate whether human monocyte-derived dendritic cells (DCs) can express p210 Bcr-Abl protein and induce antigen-specific CTL responses in vitro after transfection with total RNA of K562 cells (K562-RNA).Methods Immature DCs were derived from human peripheral blood monocytes after 5 day incubation in the presence of GM-CSF and IL-4. The cells were then transfected with K562-RNA using electroporation or DOTAP lipofection. To verify the successful transfection of DCs with K562-RNA, Bcr-Abl fusion gene expression was determined by RT-PCR and Western blot. The immune phenotypes of the DCs were analyzed by flow cytometry. CTL cytotoxicity was assayed by propidium iodide (PI) stain and flow cytometry. The amount of DCs, CD1a expression and purity of DCs were measured by FACS.Results Bcr-Abl fusion gene appeared in the DCs after transfection with K562 cell total RNA. But 24 hours later, the Bcr-Abl mRNA from the K562-RNA transfected DCs disappeared, while the cells were expressing p210 Bcr-Abl protein. The transfected DCs could significantly promote T lymphocytes to kill the target K562 cells. We found that PBMC can be induced to DC in culture medium containing human plasma, suggesting a potential for clinical application.Conclusion Human dendritic cells transfected by K562 total RNA can induce effective p210 Bcr-Abl protein-specific immune responses, which might broaden the spectrum of possible DC-based clinical applications.

Objective:To investigate the predictive value of the National Institutes of Health Stroke Scale (NIHSS) score at 24 h after endovascular treatment on the outcomes in patients with acute basilar artery occlusion (ABAO).Methods:Consecutive patients with ABAO received endovascular treatment at the Department of Neurology, Shengli Oilfield Central Hospital from January 2019 to December 2020 were retrospectively included. According to the modified Rankin Scale scores at 90 days after onset, the patients were divided into a good outcome group (0-3) and a poor outcome group (4-6), as well as a survival group and a death group. The demographic and clinical data between the groups were compared respectively. Multivariate logistic regression analysis was use to identify independent influencing factors for clinical outcomes and mortality. The predictive value of postprocedural 24 h NIHSS score on the outcomes was evaluated using the receiver operating characteristic (ROC) curves. Results:A total of 35 patients with ABAO were included. Their age was 62 years (interquartile range, 56-66 years), and 28 patients were males (80%); 19 (54.3%) had a good outcome, 16 (45.7%) had a poor outcome, and 7 (20.0%) died. Univariate analysis showed that there were statistically significant differences in hypertension, low-density lipoprotein cholesterol, fasting blood glucose, collateral circulation grading, vascular recanalization, and postprocedural 24 h NIHSS scores between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the postprocedural 24 h NIHSS score was independently correlated with the poor outcome (odds ratio 1.131, 95% confidence interval 1.017-1.258; P=0.023). Multivariate analysis did not find the independent influencing factors for death. ROC curve analysis showed that the area under the curve of the postprocedural 24 h NIHSS score for predicting poor outcome was 0.814 (95% confidence interval 0.668-0.960; P=0.011). The optimal cutoff value was 19 points, and the corresponding sensitivity and specificity were 85.7% and 71.4% respectively. Conclusions:In patients with ABAO receiving endovascular treatment, the postprocedural 24 h NIHSS score has good predictive value for poor outcomes at 90 d after procedure.

Objective:To investigate the predictive value of fasting blood glucose on clinical outcome after intravenous thrombolysis in patients with severe acute ischemic stroke (AIS).Methods:From January 2016 to November 2020, consecutive patients with severe AIS receiving intravenous thrombolysis in the Department of Neurology, Shengli Oilfield Central Hospital were enrolled retrospectively. Severe AIS was defined as the baseline National Institutes of Health Stroke Scale (NIHSS) score ≥15. The primary endpoint was the clinical outcome evaluated according to the modified Rankin Scale at 90 d after onset. 0-2 was defined as a good outcome and a score of >2 were defined as a poor outcome. The secondary endpoint events were any intracranial hemorrhage and symptomatic intracranial hemorrhage (sICH). Intracranial hemorrhage was defined as any local or distant parenchymal hemorrhage shown by craniocerebral imaging during the hospitalization. sICH was defined as any intracranial hemorrhage and the NIHSS score increased by ≥4 within 7 d after treatment. Univariate and multivariate logistic regression analysis were used to determine the independent influencing factors of various endpoint events. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of fasting blood glucose levels for endpoint events. Results:A total of 113 patients with severe AIS treated with intravenous thrombolysis were included, and 73 (64.6%) had a poor outcome; 29 (25.7%) had intracranial hemorrhage, of which 10 (8.8%) were sICH. Multivariate analysis showed that fasting blood glucose was the independent risk factors for poor outcome (odds ratio [ OR] 1.451, 95% confidence interval [ CI] 1.053-2.000; P=0.023) and sICH ( OR 1.235, 95% CI 1.013-1.504; P=0.036). The ROC curve analysis showed that the area under the curve of fasting blood glucose predicting poor clinical outcome at 90 d after onset was 0.731 (95% CI 0.637-0.824), the optimal cut-off value was 6.25 mmol/L, and the corresponding sensitivity and specificity were 63.0% and 82.5% respectively. The area under the curve of fasting blood glucose predicting sICH was 0.728 (95% CI 0.577-0.878), the optimal cut-off value was 7.98 mmol/L, and the corresponding sensitivity and specificity were 70.0% and 77.7% respectively. Conclusion:Fasting blood glucose is an independent predictor of sICH and poor outcome at 90 d after onset in patients with severe AIS receiving intravenous thrombolysis.

Objective:To investigate the clinical significance and correlation of serum alpha fetoprotein(AFP), alkaline phosphatase (ALP), and protein induced by vitamin K antagonist-Ⅱ(PIVKA-Ⅱ) in patients with primary hepatoculellar carrcinoma (PHC).Methods:A total of 72 patients with PHC who admitted to Dajiangdong Hospital from May 2017 to June 2019 were selected as observation group and they were divided into metastasis group (25 cases) and non-metastasis group (47 cases) according to the presence or absence of lymph node metastasis.Another 72 healthy people who had physical examinations during the same period were selected as the control group.The serum levels of AFP, ALP and PIVKA-Ⅱ were measured in all patients.ROC curves were used to analyze the clinical value of these three indicators in the early diagnosis and prognosis of PHC.The correlation between serum AFP, ALP, PIVKA-Ⅱ levels and clinical stage of PHC was analyzed by Pearson method.Results:The serum levels of AFP, ALP and PIVKA-Ⅱ in the observation group were significantly higher than those in the control group( t=36.64, 24.53, 47.89, P=0.012, 0.005, 0.001). The serum AFP, ALP and PIVKA-Ⅱ levels were higher in the metastasis group than in the non-metastatic group( t=20.98, 38.12, 54.17, P=0.04, 0.001, 0.000). ROC analysis showed that the serum AFP, ALP and PIVKA-Ⅱ had diagnostic value for PHC, and the combined detection had higher diagnostic efficacy ( P=0.021, 0.014, 0.003, 0.001). Compared with single index, the clinical value of three indicators in predicting whether PHC had lymph node metastasis increased significantly( P=0.036, 0.027, 0.018, 0.005). The specificity(89.57%), sensitivity(92.60%), positive predictive value(89.53%) and negative predictive value(83.75%) of the three indicators in detecting PHC increased significantly( P<0.05). Pearson analysis showed positive correlations between serum AFP, ALP, PIVKA-Ⅱ and tumor stage( P<0.05). Conclusion:Serum AFP, ALP and PIVKA-Ⅱ have certain clinical value in the early diagnosis of PHC, and the combination of these three indicators can improve the diagnostic efficacy.

Cerebrovascular diseases and cardiovascular diseases are among the top causes of death worldwide. In recent years, the concept of "brain-heart co-treatment" has gradually gained popularity. Cerebrovascular and cardiovascular diseases have similar pathological foundations, pathogenesis, comorbidities, and treatment methods. However, there is currently limited research on whether the two have a chronological order of the first onset and which is the index event of the other. However, elucidating the above issues is of great significance for the secondary prevention of cardiocerebrovascular diseases. This article reviews the correlation of onset time and influencing factors for ischemic stroke and myocardial infarction.

Objective To investigate the feasibility of using anti-sense RNA against classⅡmajor histocompatibility complex(MHCⅡ)transactivator(CⅡTA),which might regulate MHCⅡexpression,to suppress the relative immune response.Methods Stable transfectants of dermal fibroblasts with pDarⅡ(pDarⅡ-D)were tested for the expression of classic MHCⅡ(HLA-DR,-DP,-DQ)antigens induced with recombinant human interferon-gamma(IFN-?).mRNA abundance of CⅡTA,and classic MHCⅡwas mea-sured by RT-PCR.IL-2mRNA expressed in T cells,stimulated by transfected dermal fibroblasts,was de-termined by mixed lymphocyte reaction.Results When induced with IFN-?,the expression of HLA-DR and-DP antigens on pDarⅡ-D was reduced by95.63%and87.89%,respectively.Meanwhile,the mRNA contents of CⅡTA and classic MHCⅡwere decreased significantly(P

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.