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The present research focused on identifying necroptosis‐related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI‐related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis‐related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein–protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT‐PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co‐expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy. [ABSTRACT FROM AUTHOR]

This paper synthesizes the differences in the predictive power of multidimensional firm characteristics on organizational resilience and further identifies the key characteristics and their specific impact patterns. It is found that the firm's stability during the crisis depends more on the pre‐crisis firm's operating conditions, while the post‐crisis firm's flexibility depends more on the firm's internal and external resources. Besides, some firm characteristics rank higher in predicting the importance of organizational resilience. This study examines organizational resilience characteristics from a more comprehensive perspective and provides empirical evidence on how managers can better respond to systemic crises and enhance organizational resilience. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Atrial flutter (AFL) and supraventricular tachycardia (SVT) are common arrhythmias in clinic. However, some AFL cases may present additional complexities, such as both accessory pathways (AP) and dual atrioventricular node pathways, putting on a mysterious mask and making it challenging to distinguish on electrocardiograms (ECGs). A 60‐year‐old male patient had a sudden syncope, and an ECG showed wide QRS complex tachycardia. This diagnostic ambiguity is further compounded by the fact that SVT via AP conduction can exhibit wide QRS complex tachycardia characteristics resembling ventricular tachycardia (VT). Consequently, a definitive diagnosis through electrophysiological (EP) examination becomes imperative, as it dictates subsequent ablation strategies. In this article, we present a rare case involving three distinct arrhythmias including AFL, AP, and dual atrioventricular node pathways, and successfully treated through ablation. [ABSTRACT FROM AUTHOR]

The overproduction of reactive oxygen species (ROS) is one of the major reasons for the aggravation of acute lung injury (ALI). Smaller‐sized ceria nanoparticles featured with higher ROS scavenging capability than their bigger‐sized counterparts are potential candidates for ALI therapy. However, smaller‐sized ceria nanoparticles are more easily accumulated in spleen and liver rather than lung. Herein, it is reported that this obstacle can be addressed by constructing ceria into ultrafine nanowires, through which the ultrafine diameter ensures the high ROS scavenging activity and the high aspect ratio promotes the lung targeted accumulation. To demonstrate the feasibility of this conception, a platform is developed to realize length‐controlled ceria nanowires (diameter of ≈1.5 nm) synthesis. These nanowires are PEGylated using a carefully optimized procedure that can preserve their fragile crystal structures. The PEGylated nanowires exhibit higher ROS scavenging capabilities than the ≈3.9 nm sized nanoparticles. Most importantly, lung targeted accumulation can be realized through modulating the length of the nanowires, where the longer nanowires (>100 nm) show much higher lung accumulation. Due to these properties, the longer ceria nanowires can effectively scavenge the overproduced ROS during the progression of ALI, and thereby inhibit the edema and inflammation in the lung tissue. [ABSTRACT FROM AUTHOR]

Aims: To compare the performance of logistic regression and machine learning methods in predicting postoperative delirium (POD) in elderly patients. Method: This was a retrospective study of perioperative medical data from patients undergoing non‐cardiac and non‐neurology surgery over 65 years old from January 2014 to August 2019. Forty‐six perioperative variables were used to predict POD. A traditional logistic regression and five machine learning models (Random Forest, GBM, AdaBoost, XGBoost, and a stacking ensemble model) were compared by the area under the receiver operating characteristic curve (AUC‐ROC), sensitivity, specificity, and precision. Results: In total, 29,756 patients were enrolled, and the incidence of POD was 3.22% after variable screening. AUCs were 0.783 (0.765–0.8) for the logistic regression method, 0.78 for random forest, 0.76 for GBM, 0.74 for AdaBoost, 0.73 for XGBoost, and 0.77 for the stacking ensemble model. The respective sensitivities for the 6 aforementioned models were 74.2%, 72.2%, 76.8%, 63.6%, 71.6%, and 67.4%. The respective specificities for the 6 aforementioned models were 70.7%, 99.8%, 96.5%, 98.8%, 96.5%, and 96.1%. The respective precision values for the 6 aforementioned models were 7.8%, 52.3%, 55.6%, 57%, 54.5%, and 56.4%. Conclusions: The optimal application of the logistic regression model could provide quick and convenient POD risk identification to help improve the perioperative management of surgical patients because of its better sensitivity, fewer variables, and easier interpretability than the machine learning model. [ABSTRACT FROM AUTHOR]

Background: Cryoballoon ablation (CBA) is one of the most commonly used technologies designed for pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF), although the dosing of CBA remains controversial. We evaluated the long‐term efficacy and safety of a novel individualized strategy of CBA compared to radiofrequency ablation (RFA) for patients with PAF. Methods: In this observational study, symptomatic patients with drug‐refractory paroxysmal AF were prospectively consented and enrolled in four centers, being assigned either to the CBA or RFA arm for ablation. In the CBA group, we used a time to isolation (TTI) – based dosing protocol. The primary endpoint was the recurrence of atrial arrhythmia >30 s following a 90‐day blanking period. The secondary endpoint was procedure‐related complications and procedure parameters. Results: A total of 500 patients were recruited in either the CBA group (n = 247) or the RFA group (n = 253) between January 2017 and July 2018. After a median follow‐up of 778 days, the atrial tachyarrhythmia‐free survival was 71.7% in the CBA group and 67.0% in the RFA group. CBA and RFA displayed similar major or minor complication occurrence, while the former had a significantly shorter procedure duration (82.5 min vs. 141.1 min, p <.001) and left atrial dwell time (60.1 min vs. 109.9 min, p <.001) but longer fluoroscopy exposure (13.8 min vs. 8.1 min, p <.001). Conclusion: Compared to RFA, our TTI‐based CBA dosing protocol showed comparable efficacy and safety, with a significantly reduced procedure duration in patients with PAF. [ABSTRACT FROM AUTHOR]

Tripartite motif (TRIM) proteins play a regulatory function in cancer, cell apoptosis and innate immunity. To understand the role of TRIM39 in Nile tilapia (Oreochromis niloticus), TRIM39 cDNA was isolated. The total length of TRIM39 cDNA was 5025 bp. The deduced OnTRIM39 protein contains 549 amino acids and has conserved domains of the TRIM family, which are the RING, B‐box, coiled‐coil and PRY‐SPRY domains. OnTRIM39 mRNA was widely expressed in various tissues. After challenge with Streptococcus agalactiae and stimulation with polyinosinic polycytidylic acid [poly (I:C)] and lipopolysaccharides (LPS), the amount of OnTRIM39 transcript was changed in various tested tissues. OnTRIM39 overexpression increased NF‐κB activity. OnTRIM39 was present in the cytoplasm. Mass spectrometry of proteins pulled down with recombinant OnTRIM39 showed that 250 proteins potentially interact with OnTRIM39. The authors selected I3K4I3 from the 250 candidate proteins to verify its interaction with TRIM39. They also selected I3KL45, a member of the same 14‐3‐3 protein family, to verify its interaction with TRIM39. The results of pull‐down assays showed that OnTRIM39 interacted with both I3K413 and I3KL45. These results contribute to further study of the innate immune mechanism of tilapia. [ABSTRACT FROM AUTHOR]

CD19‐target chimeric antigen receptor (CAR)‐T cell therapy is highly effective for relapsed/refractory (R/R) acute lymphoblastic leukaemia (ALL), but is often complicated by cytokine release syndrome (CRS), which is potentially life‐threatening. Endothelial cells are the core regulator of CRS in many infectious diseases and may also play a key role after CAR‐T cell therapy. We provided a detailed clinical, laboratory description and endothelial cell activation biomarkers in patients with CRS. Endothelial cell activation was associated with occurrence, development and severity of CRS, manifested by decreased serum angiopoietin (Ang)‐1 levels and increased levels of von Willebrand Factor (VWF), Ang‐2, Ang‐2:Ang‐1, sE‐selectin, soluble intercellular adhesion molecule (sICAM‐1) and soluble vascular cell adhesion molecule (sVCAM)‐1. Besides, the endothelial activation was correlated with the hepatic, kidney and hematopoietic dysfunction in CRS patients. After infusion of CAR‐T cells, we detected changes of endothelial activation‐related biomarkers within 36 hours in patients who subsequently developed CRS, especially severe CRS. Using top tree models, we could predict which patients would develop CRS, especially severe CRS, or identify the severity of CRS by certain biomarkers of endothelial activation. These data provide a new idea and will help identify new targets for early intervention and prevention of CRS. [ABSTRACT FROM AUTHOR]

Deep learning (DL) has been applied to digital signal modulation identification (DSMI) due to its powerful feature learning ability. However, most of the existing DL‐based DSMI methods are limited to specific experimental scene relating to the additive white Gaussian noise (AWGN) channel or static multipath channel. The result is that the trained network has deteriorative identification accuracy when the channel conditions change unless retrained. To solve the problem, this paper proposes a DSMI method suitable for orthogonal frequency division multiplexing (OFDM) under different multipath channels, including the variation of delay, path number and channel coefficient. This method can accurately detect the modulation feature rather than the channel's to identify the modulation type, thus reducing the network training amount. The method is divided into two parts. Firstly, traditional signal processing methods are combined, including various channel estimators and equalisers to compensate for the channel. Then a robust DL network, RSN‐MI, is designed as a classifier. Unlike other DL‐based DSMI methods, the influence of signal processing algorithms on DSMI performance are focused on rather than model parameters. Besides, the proposed classifier is compared with the DSMI classifier in other contributions. The results show that the classifier works better in different multipath channels. [ABSTRACT FROM AUTHOR]

Introduction: Anti‐CD19 chimeric antigen receptor (CAR) ‐T cells, which recognize and kill both B lymphoblasts and normal B cells, result in B cell aplasia and humoral immunodeficiency. However, there were only a few detailed reports on the profile of immune reconstitution after anti‐CD19 CAR‐T cell therapy. Methods: Thirty nine patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (ALL) receiving anti‐CD19 CAR‐T cell therapy were enrolled. Subjects died, relapsed, received other treatment, or lost to follow‐up within 60 days post‐infusion were excluded. 21 patients were finally selected. Laboratory and clinical data were collected for analysis of immune reconstitution. Results: CD8+ cells were the first to recover with a median time on day 21(7‐87), followed by CD16/CD56+ cells on day 28(14‐87), and finally CD4+ cells with only 5(23.81%) patients recovered within 60 days post‐infusion. CD4/CD8 ratio was inverted, sustaining for at least 1 year. B cell aplasia occurred in all patients and CD19+ cells returned to normal on a median time of day 79(41‐118). All patients developed hypogammaglobulinemia with a median onset time of 2 weeks post‐infusion. IgG recovered in 6 patients with a median time on day 184(89‐346). IgM recovered on days 212, 242, and 346 in 3 patients. IgA recovered most slowly and remained low >1 year postinfusion. A total of 9 infections occurred in 6(28.57%) patients. Conclusions: Our data showed prolonged reconstitution of immune function, especially humoral immunity, in R/R B cell ALL patients receiving anti‐CD19 CAR‐T cell therapy. [ABSTRACT FROM AUTHOR]

Purpose: Anti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 and anti‐CD20 CAR‐T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity. Methods: Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti‐CD19 and anti‐CD20 CAR‐T cells. Treatment response, toxicity, and persistence were monitored continuously. Results: Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%‐94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%‐74.3%) had a complete response (CR). Peak levels of anti‐CD19 and anti‐CD20 CAR cells were associated with response (P =.007 and.002). Grade 3‐4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression‐free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level. Conclusions: Coadministration of anti‐CD19 and CD20 CAR‐T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178. [ABSTRACT FROM AUTHOR]

Residual dipolar couplings (RDC) emerged to be an important structural parameter for organic and biomolecules. Herein, a new helical polyisocyanopeptide ( l,l-PIAF-OBn) that forms lyotropic liquid crystals (LLC) in CDCl3 is proposed as a novel weakly orienting medium for acquiring residual dipolar couplings (RDCs) of organic molecules. We demonstrate its application for the structural elucidation of strychnine and triptolide. [ABSTRACT FROM AUTHOR]

Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO-1 and Kasumi-1 cells. HAA caused cleavage of the AML1-ETO (AE) oncoprotein to form truncated AE (ΔAE). Pretreatment with the caspase-3 inhibitor caspase-3 inhibitor Q-DEVD-OPh (QDO) not only suppressed HAA-induced apoptosis but also abrogated the cleavage of AE and generation of ΔAE. These results suggest that HAA synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein, thus providing direct evidence for the strong activity of HAA toward t(8;21) AML. [ABSTRACT FROM AUTHOR]

Residual dipolar couplings (RDCs) have attracted attention in light of their great impact on the structural elucidation of organic molecules. However, the effectiveness of RDC measurements is limited by the shortage of alignment media compatible with widely used organic solvents, such as DMSO. Herein, we present the first liquid crystal (LC) based alignment medium that is compatible with pure DMSO, thus enabling RDC measurements of polar and intermediate polarity molecules. The liquid crystals were obtained by grafting polymer brushes onto graphene oxide (GO) using free radical polymerization. The resulting new medium offers several advantages, such as absence of background signals, narrow line shapes, and tunable alignment. Importantly, this medium is compatible with π-conjugated molecules. Moreover, sonication-induced fragmentation can reduce the size of GO sheets. The resulting anisotropic medium has moderate alignment strength, which is a prerequisite for an accurate RDC measurement. [ABSTRACT FROM AUTHOR]

This study examined the effects of perioperative dexmedetomidine treatment on physiological modulators of surgical stress response. The quality of the included studies was assessed prior to performing meta-analyses of the weighted mean differences in the changes from baseline of stress hormones and interpreted in the light of statistical heterogeneity between the studies. Nineteen studies (844 surgical subjects) data were used for this meta-analysis. Dexmedetomidine administration significantly decreased blood cortisol levels ( μg/ dL) postoperatively (mean difference with 95% confidence interval ( CI) from controls: −18.78 (−28.45, −9.10); P < 0.05). In the subgroup analysis, the mean difference between dexmedetomidine-treated and saline-treated subjects in the changes from baseline of the cortisol levels was −20.10 (−30.96, −9.25; P < 0.05) but, between dexmedetomidine- and comparator-treated subjects, it was not statistically significantly different (−15.13 (−49.78, 19.52); P < 0.05). Compared with controls, dexmedetomidine treatment also decreased adrenaline and noradrenaline levels significantly (mean difference in the percent changes from baseline: −90.41 (−145.79, −35.03)%; P < 0.05 and −62.82 (−85.47, −0.40.17)%; P < 0.05, respectively). Dexmedetomidine also decreased prolactin levels with a mean difference of −19.42 (−39.37, 0.52) μg/L ( P = 0.06). In conclusion, perioperative use of dexmedetomidine reduces serum catecholamine and cortisol levels but the decrease in cortisol levels was not statistically different from the comparator anaesthetics. More data will be required to assess the effects of dexmedetomidine on corticotropin, prolactin, and growth hormone. [ABSTRACT FROM AUTHOR]

The article presents a surface texturing and femtosecond laser doping technology for dental implants. A thin layer was predeposited on the surface of titanium and adopted a femtosecond laser to ablate the composite surface. The doping concentration is controllable through the seeded silver layer thickness. The effectiveness of the technology was proved by cytotoxicity, antibacterial and acid aging experiments.

Percutaneous Lead Revision for Cardiac Perforation Introduction Cardiac perforation is an infrequent but potentially life-threatening complication associated with placement of a cardiac implantable electronic device (CIED). The objective of this study was to determine the outcomes of percutaneous lead revision in patients who had lead perforation of the myocardium after CIED placement. Methods and Results We reviewed records of 1,458 patients who underwent CIED lead extraction or repositioning. Of these, 31 (2.1%) had the procedure performed for lead perforation as a complication of CIED placement. Demographic, clinical, and follow-up characteristics of the patients were analyzed. Mean (SD) patient age was 65 (23) years. Cardiac perforation was detected within 24 hours after implantation in 9 patients, within 1 month in 17, and greater than 1 month in 5. Pericardiocentesis was performed with a pigtail drainage catheter in place before the lead revision in 17 patients (55%) who had pericardial effusion, with or without hemodynamic compromise. All culprit leads were successfully managed with percutaneous lead removal (n = 3 [10%]), new lead placement (n = 12 [38%]), or lead repositioning (n = 16 [52%]). Of the 17 patients with pericardiocentesis before the reoperation, none had tamponade develop; in contrast, 3 of the remaining 14 patients had tamponade develop and required urgent pericardiocentesis. All patients survived without requiring open chest surgery. Conclusion Percutaneous removal or repositioning of the perforating lead is feasible and appears effective. Placement of a prophylactic pericardial drain catheter may reduce the incidence of urgent pericardiocentesis during or after a procedure. [ABSTRACT FROM AUTHOR]

We report a case of sinus tachycardia with perpetuating slow pathway (SP) conduction in a 42-year-old woman who developed severe symptoms as a result of atrioventricular (AV) desynchronization. The restoration of an AV synchrony, achieved with selective radiofrequency ablation of the SP, eliminated the symptomatic arrhythmia and may represent a reasonable therapeutic option despite the fact that the patient has no AV-node reentrant tachycardia. This case demonstrates the importance of AV timing. [ABSTRACT FROM AUTHOR]

With the number of complex catheter ablation procedures increasing, procedure-related acute cardiac tamponade is encountered more frequently in the cardiac catheterization laboratory. Survival depends on prompt recognition and rescue pericardiocentesis. The aim of this report was to validate fluoroscopic heart silhouette characteristics associated with cardiac tamponade as a diagnostic method, and evaluate the safety and effectiveness of fluoroscopy-guided pericardiocentesis during catheter ablation. All cases of acute cardiac tamponade that occurred in the cardiac catheterization laboratory during radiofrequency catheter ablation from March 2004 to November 2009 were reviewed retrospectively. Of 1,832 catheter ablation procedures performed during a 5-year period, 10 (0.55%) were complicated by cardiac tamponade. Fluoroscopic examination confirmed the diagnosis in all 10 patients and demonstrated effusions before hypotension in four patients. All patients were stabilized by fluoroscopy-guided pericardiocentesis with placement of an indwelling catheter and autologous transfusion. The time interval between recognition of cardiac tamponade and completion of pericardiocentesis was 6.0 ± 1.8 minutes (range 3-9 minutes). The mean aspirated blood volume was 437 mL (range 110-1,400 mL), and the mean autotransfused blood volume was 425 mL (range 100-1,384 mL). Surgical repair of the cardiac perforation was needed in one patient. No procedure-related death occurred. A reduction in the excursion of cardiac silhouette on fluoroscopy is an early diagnostic sign of cardiac tamponade during radiofrequency ablation. Fluoroscopy-guided pericardiocentesis is a safe and effective management strategy for cardiac tamponade developed in the cardiac catheterization laboratory. (PACE 2011; 9-14) [ABSTRACT FROM AUTHOR]

A partially filled waveguide is presented to measure complex permittivity and permeability simultaneously at microwave frequency in this article. The mode-matching method is used to analyze the higher-order modes in the waveguide. Experimental results agree well with theoretical results. [ABSTRACT FROM AUTHOR]

A six-port technique is presented for simultaneous measurement of complex permittivity and permeability of a given material. A dual six-port network analyzer is employed to measure the scattering parameters. The complex permittivity and permeability are computed from the scattering parameters of a transmission line filled with the material to be tested. Measured &epsilonr;, μr data for Teflon agree well with known values. The identical samples are measured with a six-port ANA and an automatic network analyzer, HP8510B. The measured data of the six-port ANA and the HP8510B agree well with each other by comparison. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by autoantibody‐mediated platelet destruction. Multiple factors have been implicated in ITP pathogenesis, including T‐lymphocyte dysfunctions. Increasing studies have indicated that stem cell memory‐like T cell (TSCM) plays an important role in the development of multiple autoimmune diseases. This study aimed to explore the clinical correlation between the TSCM subset and ITP. The percentages of peripheral blood naïve T cells (TNs), TSCMs, central memory T cells (TCMs), effector memory T cells (TEMs) and effector T cells (TEs) among CD4+ and CD8+ T cells in 20 ITP patients before and after treatment were detected using flow cytometry. Our results showed that the percentages of peripheral blood CD4+ and CD8+ T cells in ITP patients were imbalanced. The percentage of CD8+ TSCMs in peripheral blood before treatment in ITP patients was significantly higher than that in healthy controls, whereas the percentages of the other T cell subsets did not exhibit significant differences. Our study further analysed the correlation between the change in the percentage of CD8+ TSCMs and the treatment efficacy. The results showed that the percentage of peripheral blood CD8+ TSCMs in ITP patients after glucocorticoid treatment significantly decreased and the changes of the percentages of CD8+ TSCMs before and after treatment in complete response (CR) and response (R) patients were obvious. Our finding showed that the imbalance of the percentage of CD8+ TSCMs might be involved in the development of ITP and might serve as a novel indicator of efficacy. [ABSTRACT FROM AUTHOR]

The article discusses a 16-year-old female patient who underwent catheter ablation after presenting with a four-year history of recurrent supraventricular tachycardia. Following catheterization and three radio frequency (RF) energy applications during sinus rhythm, another type of tachycardia was induced. After relocation of the coronary sinus (CS) catheter, the CS3-4 electrodes indicated double atrial potentials with a 40-millisecond interval. The changed tachycardia mechanism is examined.

Phase relationships in the title system at 1200 °C are determined by powder XRD. [ABSTRACT FROM AUTHOR]

A correction to the article "Effects of Thermal Annealing on the Structure of Ferroelectric Thin Films," published in the 2006 issue is presented.

CD19-targeted chimeric antigen receptor T (CAR-T) cells using murine single-chain variable fragment (scFv) has shown substantial clinical efficacy in treating relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, potential immunogenicity of the murine scFv domain may limit the persistence of CAR-T cells. In this study, we treated 52 consecutive subjects with R/R ALL with humanized CD19-specific CAR-T cells (hCART19s). Forty-six subjects achieved complete remission (CR) (N = 43) or CR with incomplete count recovery (CRi) (N = 3) within 1 month post infusion. During the follow-up with a median time of 20 months, the 1-year cumulative incidence of relapse was 25% (95% confidence interval [CI] 13-46), and 1-year event-free survival was 45% (95% CI 29-60). To the cutoff date, 20 patients presented CD19 + relapse and 2 had CD19 - relapse. Among the 22 relapsed patients, 14 had treatment-mediated and treatment-boosted antidrug antibodies (ADA) as detected in a sensitive and specific cell-based assay. ADA positivity was correlated with the disease relapse risk. ADA-positive patients had a significantly lower CAR copy number than ADA-negative patients at the time of recurrence (p < .001). In conclusion, hCART19s therapy is safe and highly active in R/R ALL patients, and the hCART19s treatment could induce the emergence of ADA, which is related to the recurrence of the primary disease., (© 2022 Wiley Periodicals LLC.)

Aim: To investigate bilirubin UDP-glucuronosyltransferase (UGT1A1) gene allele in healthy Chinese neonates, their cord bilirubin level and the subsequent hyperbilirubinemia to determine relationships among them., Methods: Cord blood of 48 neonates was obtained to determine the exon 1 of UGT1A1 gene, total serum bilirubin, albumin, glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT) and haemoglobin (Hb) concentration. Neonatal jaundice was assessed by measurement of transcutaneous bilirubin (TCB) and serum bilirubin. Neonates were divided into two groups according to mutant or normal allele to compare the variables., Results: Nineteen infants had the nucleotide 211 G-->A allele, 3 had the heterozygous variation (686C-->A, 845 A-->T, 231G-->A). In the 211 A allele group, cord bilirubin was significantly higher than in the 211 G allele group (p = 0.034), but there were no differences in albumin (p = 0.678), GPT (p = 0.460), GOT (p = 0.440) and Hb (p = 0.886). The TCB (at 48, 96 h), the frequency of the hyperbilirubinemia and prolonged jaundice were also significantly higher in the 211 A allele group., Conclusions: The UGT1A1 gene codon G71R allele is a risk factor for neonatal hyperbilirubinemia in the Chinese population. Its effect on bilirubin metabolism may present early on, as well as late in foetal life.