[Recent research on chimeric antigen receptor T cells in children with refractory/relapsed acute lymphoblastic leukemia]. / 嵌合抗原受体Tç»†èƒžåœ¨å„¿ç«¥å¤å‘éš¾æ²»æ€§æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— ä¸­çš„ç ”ç©¶è¿›å±•.

At present, the treatment of refractory/relapsed acute lymphoblastic leukemia is still in a difficult situation, and even if the intensity of chemotherapy is increased or it is combined with hematopoietic stem cell transplantation, some children may have a poor prognosis and a short survival time. Chimeric antigen receptor T-cell (CAR-T) immunotherapy uses genetically engineered T cells and does not rely on the human leukocyte antigen pathway to recognize tumor-specific antigens, and then CAR-T cells bind to target antigen cells to trigger immune response, thereby exerting a sustained anti-leukemia effect. As the most rapidly developed tumor immunotherapy, major breakthroughs have been made for CAR-T cells in the treatment of various hematological tumors, but there still lacks a comprehensive system for the research, development, and production of CAR-T cells and standardized diagnosis and treatment protocols in China. This article reviews the recent research on CAR-T cells in children with refractory/relapsed acute lymphoblastic leukemia.

Preoperative QRS Duration Predicts the Responsiveness of Chronic Heart Failure Patients with Pacemaker Indications to Left Bundle Branch Area Pacing Treatment.

BACKGROUND: This study investigated the predictive value of preoperative QRS duration (QRSd) in responsiveness of chronic heart failure (CHF) patients with pacemaker indications to the left bundle branch area pacing (LBBAP). METHODS: Thirty-one CHF patients with cardiac function categorized as NYHA class II or above and indications for pacemaker therapy who successfully underwent LBBAP treatment were enrolled in this study. Based on the 12-month postoperative responsiveness to treatment, patients were divided into a responsiveness group (N = 16) and a no-responsiveness group (N = 15). Data from all patients were collected for analysis. Multivariate binary logistic regression analysis was used to determine the independent factors associated with the responsiveness to LBBAP treatment. RESULTS: Among the 31 patients with LBBAP, 16 patients (51.6%) responded to the treatment, and 15 patients (48.4%) had no response. There were significant differences between the two groups with regard to complete left bundle branch block (CLBBB), preoperative QRSd, and preoperative left ventricular peak time (LVAT). Univariate logistic regression analysis showed that CLBBB, preoperative QRSd, and preoperative LVAT all were significantly correlated with responsiveness to LBBAP. Multivariate binary logistic regression analysis showed that QRSd was an independent predictor of responsiveness to LBBAP. The maximum area under the ROC curve for QRSd was 0.827 (95%C.I.:0.663-0.991), the maximum Youden index was 0.679, with the optimal cutoff point of QRSd ≥ 153 ms, a sensitivity of 81.3%, and a specificity of 86.7%. CONCLUSION: Preoperative QRSd predicts the responsiveness of CHF patients with pacemaker indications to LBBAP.

Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis.

BACKGROUND: Studies have found that circular RNAs (circRNAs) play key roles in cardiovascular diseases. However, the function of circROBO2 in acute myocardial infarction (AMI) is unclear. This study aimed to investigate the pathogenesis of circROBO2 in AMI. METHODS: qRT-PCR and Western blot were used to determine the expression levels of circROBO2, miR-1184, and TRADD in AMI and sham-operated mouse models at mRNA and protein level, respectively. The relationship among miR-1184, circROBO2 and TRADD was evaluated by RNA immunoprecipitation (RIP) analysis and luciferase reporter gene analysis. The roles of circROBO2, miR-1184, and TRADD in myocardial cell apoptosis were evaluated using flow cytometry. Ultrasound echocardiography, serum creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH), myocardial infarction area, and myocardial cell apoptosis were measured to examine the effects of circROBO2 on myocardial injury. RESULTS: The expression levels of miR-1184 were significantly reduced, and the expression levels of circROBO2 and TRADD were significantly increased in MI group. CircROBO2 acted as a sponge for miR-1184 by upregulating the expression of TRADD. In addition, overexpression of miR-1184 enhanced the protective effect of knockdown of circROBO2 by partially inhibiting the expression of TRADD in vivo and in vitro. CONCLUSION: Knockdown of circROBO2 reduced the apoptosis of cardiomyocytes by increasing the expression levels of miR-1184, which in turn decreased the expression levels of TRADD in the myocardium post-MI.

Development and validation of a novel nomogram for predicting overall survival patients with neuroblastoma.

PURPOSE: The aim of this study was to develop a nomogram specially for predicting overall survival (OS) for Chinese patients with neuroblastoma (NB). METHODS: Patients with pathologically confirmed NB who were newly diagnosed and received treatments at our hospital from October 2013 to October 2021 were retrospectively reviewed. The nomogram for OS were built based on Cox regression analysis. The validation of the prognostic model was evaluated by concordance index (C-index), calibration curves, and decision curve analyses (DCAs). RESULTS: A total of 254 patients with NB were included in this study. They were randomly divided into a training cohort (n = 178) and a validation cohort (n = 76) at a ratio of 7:3. Multivariate analyses revealed that prognostic variables significantly related to the OS were age at diagnosis, bone metastasis, hepatic metastasis, INSS stage, MYCN status and DNA ploidy. The nomogram was constructed based on above 6 factors. The C-index values of the nomogram for predicting 3-year and 5-year OS were 0.926 and 0.964, respectively. The calibration curves of the nomogram showed good consistency between nomogram prediction and actual survival. The DCAs showed great clinical usefulness of the nomograms. Furthermore, patients with low-risk identified by our nomogram had much higher OS than those with high-risk (p < 0.001). CONCLUSION: The nomogram we constructed exhibited good predictive performance and could be used to assist clinicians in their decision-making process.

[The Effects of IGHG1 on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia THP-1 Cells].

OBJECTIVE: To investigate the effects of the immunoglobulin G1 heavy chain constant region (IGHG1) on the proliferation and apoptosis of acute myeloid leukemia (AML) THP-1 cells and its possible mechanism of action. METHODS: Human AML THP-1 cells were cultured in vitro and divided into control (normally cultured THP-1 cells), pcDNA3.1 ï¼»THP-1 cells transfected with IGHG1 overexpression (pcDNA3.1-IGHG1) negative control plasmidï¼½, pcDNA3.1-IGHG1 (THP-1 cells transfected with plasmid containing pcDNA3.1-IGHG1), LY364947 ï¼»transforming growth factor-ß (TGF-ß)/signal transduction protein (Smad) inhibitor LY364947 20 µmol/L treated THP-1 cellsï¼½, si-NC ï¼»THP-1 cells transfected with IGHG1-small interfering RNA (siRNA) negative controlï¼½, si-IGHG1 (THP-1 cells transfected with IGHG1-siRNA), and si-IGHG1+LY364947 (IGHG1-siRNA and LY364947 co-treated THP-1 cells) a total of 7 groups. Fluorescence quantitative PCR was used to detect the expression of IGHG1 and immunoglobulin G (IgG) mRNA of THP-1 cells in each group; CCK-8 was used to detect THP-1 cells proliferation activity; flow cytometry was used to detect THP-1 cells apoptosis and cell cycle in each group; Western blot was used to detect the THP-1 cells proliferation, apoptosis and the expression of TGF-ß/Smad signaling pathway related proteins. RESULTS: Compared with the control group, after overexpression of IGHG1, the expression of IGHG1 and IgG mRNA, cell proliferation viability, S phase cell ratio, expressions of Cyclin D1, B cell lymphoma-2 (Bcl-2), IgG, TGF-ß1, phosphorylated Smad3 (p-Smad3)/Smad3 protein in THP-1 cells were significantly increased (P<0.05), the apoptosis rate, G0/G1 phase cell ratio, expression of p21, Bcl-2 related X protein (Bax), Caspase-3 protein were significantly reduced (P<0.05); after inhibiting TGF-ß/Smad signaling pathway or silencing IGHG1, the expression of IGHG1 and IgG mRNA, cell proliferation viability, S phase cell ratio, expression of Cyclin D1, Bcl-2, IgG, TGF-ß1, p-Smad3/Smad3 protein in THP-1 cells were significantly reduced (P<0.05), the apoptosis rate, G0/G1 phase cell ratio, expressions of p21, Bax, and Caspase-3 protein were significantly increased (P<0.05); and compared with silencing IGHG1, after co-treatment of IGHG1 gene silencing and TGF-ß/Smad pathway inhibition, the expression of IGHG1 and IgG mRNA, cell proliferation viability, S phase cell ratio, expressions of Cyclin D1, Bcl-2, IgG, TGF-ß1, p-Smad3/Smad3 protein in THP-1 cells were significantly reduced (P<0.05), the apoptosis rate, G0/G1 phase cell ratio, expression of p21, Bax, and Caspase-3 protein were significantly increased (P<0.05). CONCLUSION: Silencing IGHG1 gene can down-regulate the expression of IgG, inhibit the proliferation of human AML THP-1 cells, block cell cycle progression, and induce cell apoptosis; its mechanism may be related to the inhibition of the TGF-ß/Smad pathway activation.

The Implantation of Left Bundle Branch Area Pacing in Patients with and without Bundle Branch Block.

OBJECTIVE: To investigate the clinical safety and electrocardiogram (ECG) characteristics in patients with left bundle branch area pacing (LBBAP). STUDY DESIGN: Retrospective study. PLACE AND DURATION OF STUDY: Department of Cardiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, from May 2018 to January 2020. METHODOLOGY: Patients scheduled for Left Bandle Branch Area Pacing (LBBAP), who were admitted due to bradycardia, had been prospectively recruited. The Medtronic 3830 pacing lead was first placed at the right ventricular (RV) side of the interventricular septum (IVS) with pacing parameters (pacing threshold, pacing impedance and sensing amplitude) and ECG characteristics [QRS morphology, paced QRS duration and stimulus to peak left ventricular activation time (Sti-LVAT)] measured, which was called the right ventricular septum pacing group (RVSP). Then the pacing lead was screwed towards the left ventricular (LV) side of the IVS; and the corresponding parameters and ECG characteristics were assessed, which was called LBBAP group. RESULTS: RVSP caused left bundle block (LBBB) morphology on ECG, while pacing at left bundle area led to right bundle branch block (RBBB) morphology, without remarkable difference in pacing threshold and pacing impedance. The sensing amplitude during LBBAP was significantly higher compared with RVSP (p <0.05). QRS duration and Sti-LVAT were significantly shorter when paced on LBBAP compared with RVSP (p <0.05). Patients with LBBB morphology in intrinsic rhythm showed the greatest reduction in paced QRS duration and Sti-LVAT compared to patients with RBBB morphology or no bundle branch block morphology (p <0.001). There were no complications during pacemaker implantation and no adverse events observed during follow-up. The pacing parameters remained stable during the follow-up (9.2 ± 3.7 months). CONCLUSION: Compared with pacing on RVSP, patients with LBBAP showed RBBB morphology with significantly reduced QRS duration and LV Sti-LVAT under similar pacing parameters. LBBAP is safe and feasible and may be a promising strategy for patients with LBBB morphology who are indicated for ventricular pacing. Key Words: Physiological pacing, Left bundle branch pacing, Right ventricular pacing, Left bundle branch block, Pacemaker.

[Effects of simvastatin on aortic vascular endothelial cell apoptosis and Bcl-2 protein expression in a rat model of atherosclerosis].

OBJECTIVE: To explore the effects of simvastatin on vascular endothelial cell apoptosis and Bcl-2 protein expression in the aorta in a rat model of atherosclerosis. METHODS: Thirty-six rats were randomized into control group (n=10), atherosclerosis model group (n=13) and simvastatin intervention group (n=13). In the latter two groups, rat models of atherosclerosis were established by intraperitoneal injection of vitamin D3 combined with high-fat feeding for 6 weeks, and the control rats were fed with regular diet. In the intervention group, the rats were further fed with high-fat diet with daily simvastatin treatment for 4 weeks. After the treatments, the pathological changes and plaque in the thoracic aorta were observed, and the expression of Bcl-2 protein was detected with immunohistochemistry. TUNEL assay was used to determine the apoptosis index (AI) of the vascular endothelial cells. RESULTS: Compared with that in the control group, Bcl-2 protein expression in the aorta of atherosclerotic rats was significantly decreased (P<0.05); simvastatin treatment obviously increased the expression of Bcl-2 protein in atherosclerotic rats (P<0.05) to a level similar to that in the control group. The AI was the highest in the model group (P<0.05) and comparable between the control and simvastatin treatment group. CONCLUSION: The therapeutic effect of simvastatin against atherosclerosis is probably mediated by up-regulation of Bcl-2 protein, which inhibits vascular endothelial cell apoptosis in rats with aortic atherosclerosis.

Stability Analysis of Learning Algorithms for Blind Source Separation.

Recently a number of adaptive learning algorithms have been proposed for blind source separation. Although the underlying principles and approaches are different, most of them have very similar forms. Two important issues remained to be elucidated further: the statistical efficiency and the stability of learning algorithms. The present letter analyzes a general form of statistically efficient algorithms and gives a necessary and sufficient condition for the separating solution to be a stable equilibrium of a general learning algorithm. Moreover, when the separating solution is unstable, a simple method is given for stabilizing the separating solution by modifying the algorithm.