Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation.

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Background-Pulmonary veins (PVs) can be completely isolated with continuous circular lesions (CCLs) around the ipsilateral PVs. However, electrophysiological findings have not been described in detail during ablation of persistent atrial fibrillation (AF). Methods and Results-Forty patients with symptomatic persistent AF underwent complete isolation of the right-sided and left-sided ipsilateral PVs guided by 3D mapping and double Lasso technique during AF. Irrigated ablation was initially performed in the right-sided CCLs and subsequently in the left-sided CCLs. After complete isolation of both lateral PVs, stable sinus rhythm was achieved after AF termination in 12 patients; AF persisted and required cardioversion in 18 patients. In the remaining 10 patients, AF changed to left macroreentrant atrial tachycardia in 6 and common-type atrial flutter in 4 patients. All atrial tachycardias were successfully terminated during the procedure. Atrial tachyarrhythmias recurred in 15 of 40 patients at a median of 4 days after the initial ablation. A repeat ablation was performed at a median of 35 days after the initial procedure in 14 patients. During the repeat study, recovered PV conduction was found in 13 patients and successfully abolished by focal ablation of the conduction gap of the previous CCLs. After a mean of 8Ϯ2 months of follow-up, 38 (95%) of the 40 patients were free of AF. Conclusions-In patients with persistent AF, CCLs can result in either AF termination or conversion to macroreentrant atrial tachycardia in 55% of the patients. In addition, recovered PV conduction after the initial procedure is a dominant finding in recurrent atrial tachyarrhythmias and can be successfully abolished. (Circulation. 2005;112:3038-3048.)

The plant hormone abscisic acid (ABA) play essential roles in numerous physiological processes such as seed dormancy, seed germination, seeding growth and responses to biotic and abiotic stresses. Such biological processes are tightly controlled by a complicated regulatory network including ABA homoeostasis, signal transduction as well as cross-talking among other signaling pathways. It is known that ABA homoeostasis modulated by its production, inactivation, and transport pathways is considered to be of great importance for plant development and stress responses. Most of the enzymes and transporters involved in ABA homoeostasis have been largely characterized and they all work synergistically to maintain ABA level in plants. Increasing evidence have suggested that transcriptional regulation of the genes involved in either ABA production or ABA inactivation plays vital roles in ABA homoeostasis. In addition to transcription factors, such progress is also regulated by microRNAs and newly characterized root to shoot mobile peptide-receptor like kinase (RLKs) mediated long-distance signal transduction. Thus, ABA contents are always kept in a dynamic balance. In this review, we survey recent research on ABA production, inactivation and transport pathways, and summarize some latest findings about the mechanisms that regulate ABA homoeostasis.

Chimeric antigen receptor T (CAR-T) cell therapy has shown promising results for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). The immune response induced by murine single-chain variable fragment (scFv) of the CAR may limit CAR-T cell persistence and thus increases the risk of leukemia relapse. In this study, we developed a novel humanized scFv from the murine FMC63 antibody. A total of 18 R/R ALL patients with or without prior murine CD19 CAR-T therapy were treated with humanized CD19-targeted CAR-T cells (hCART19s). After lymphodepletion chemotherapy with cyclophosphamide and fludarabine, the patients received a single dose (1 × 10 /kg) of autologous hCART19s infusion. Among the 14 patients without previous CAR-T therapy, 13 (92.9%) achieved complete remission (CR) or CR with incomplete count recovery (CRi) on day 30, whereas 1 of the 3 patients who failed a second murine CAR-T infusion achieved CR after hCART19s infusion. At day 180, the overall and leukemia-free survival rates were 65.8% and 71.4%, respectively. The cumulative incidence of relapse was 22.6%, and the nonrelapse mortality rate was 7.1%. During treatment, 13 patients developed grade 1-2 cytokine release syndrome (CRS), 4 patients developed grade 3-5 CRS, and 1 patient experienced reversible neurotoxicity. These results indicated that hCART19s could induce remission in patients with R/R B-ALL, especially in patients who received a reinfusion of murine CAR-T.

Gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD), is one of the most lethal malignancies in the world. It is vital to classify and detect the hub genes and key pathways participated in the initiation and progression of GAC. In this study, we collected and sequenced 15 pairs of GAC tumor tissues and the adjacent normal tissues. Differentially expressed genes (DEGs) were analyzed and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis were used to annotate the unique biological significance and important pathways of enriched DEGs. Moreover, we constructed the protein-protein interaction (PPI) network by Cytoscape and conducted KEGG enrichment analysis of the prime module. We further applied the TCGA database to start the survival analysis of these hub genes by Kaplan-Meier estimates. Finally, we obtained total 233 DEGs consisted of 64 up-regulated genes and 169 down-regulated genes. GO enrichment analysis found that DEGs most significantly enriched in single organism process, extracellular region, and extracellular region part. KEGG pathway enrichment analysis suggested that DEGs most significantly enriched in Protein digestion and absorption, Gastric acid secretion, and ECM-receptor interaction. Furthermore, the PPI network showed that the top 10 hub genes in GAC were IL8, COL1A1, MMP9, SST, COL1A2, TIMP1, FN1, SPARC, ALDH1A1, and SERPINE1 respectively. The prime gene interaction module in PPI network was enriched in protein digestion and absorption, ECM receptor interaction, the PI3K-Akt signaling pathway, and pathway in cancer. Survival analysis based on the TCGA database found that the expression of the FN1, SERPINE1, and SPARC significantly predicted poor prognosis of GAC. Collectively, we identified several hub genes and key pathways associated with GAC initiation and progression by analyzing the microarray data on DEGs, which provided a detailed molecular mechanism underlying GAC occurrence and progression.

This randomized trial was performed to investigate the efficacy of low-dose rituximab in combination with glucocorticoids for treatment of patients with immune thrombocytopenia (ITP). Sixty-two patients were randomly separated into the glucocorticoids (control) and the experimental (glucocorticoids + rituximab) groups. Patients in both groups received dexamethasone 40 mg/day on days 1-4, followed by decrements of prednisone 60, 30, 15, 10 mg/day on days 5-7, 8-14, 15-21, 22-28, respectively. Patients in the experimental group also received rituximab 100 mg on days 7, 14, 21, 28. The overall response (OR) was similar in both groups at day 28 (experimental group vs. glucocorticoids group: 80.6 vs. 74.2%, P = .938); however, sustained response (SR) was more pronounced in the experimental group as compared to that in the glucocorticoids group (77.4 vs. 38.7%, P < .001). Both groups showed similar incidence of adverse events (experimental group vs. glucocorticoids group: 9.7 vs. 6.5%, P = .325). As expected, B cell depletion was seen in the experimental group. In addition, both groups experienced a significant up-regulation in Treg cell levels, but the up-regulation in the experimental group was maintained at an even higher level and persisted a longer time than those in the glucocorticoids group. Thus, low-dose rituximab combined with short-term glucocorticoids provides an alternative treatment for ITP prior to splenectomy.

EBV causes B lymphomas and undifferentiated nasopharyngeal carcinoma (NPC). Although the mechanisms by which EBV infects B lymphocytes have been extensively studied, investigation of the mechanisms by which EBV infects nasopharyngeal epithelial cells (NPECs) has only recently been enabled by the successful growth of B lymphoma Mo-MLV insertion region 1 homolog (BMI1)-immortalized NPECs in vitro and the discovery that neuropilin 1 expression positively affects EBV glycoprotein B (gB)-mediated infection and tyrosine kinase activations in enhancing EBV infection of BMI1-immortalized NPECs. We have now found that even though EBV infected NPECs grown as a monolayer at extremely low efficiency (<3%), close to 30% of NPECs grown as sphere-like cells (SLCs) were infected by EBV. We also identified nonmuscle myosin heavy chain IIA (NMHC-IIA) as another NPEC protein important for efficient EBV infection. EBV gH/gL specifically interacted with NMHC-IIA both in vitro and in vivo. NMHC-IIA densely aggregated on the surface of NPEC SLCs and colocalized with EBV. EBV infection of NPEC SLCs was significantly reduced by NMHC-IIA siRNA knock-down. NMHC-IIA antisera also efficiently blocked EBV infection. These data indicate that NMHC-IIA is an important factor for EBV NPEC infection. Epstein-Barr virusBV is a nearly ubiquitous human γ-herpesvirus that causes B-cell lymphomas and nasopharyngeal carcinoma (NPC), indicative of tropism for both cell types (1-3). Until recently, the molecular mechanisms of EBV infection of B lymphocytes were better understood than the mechanisms of epithelial cell infection (4). EBV attachment to the B-cell membrane is mediated by interactions between EBV glycoprotein 350 (gp350) and complement receptor type 2 (CR2 or CD21) (5) or CD35 (6). EBV gp42 binding to HLA class II triggers EBV fusion with B cells in the presence of EBV glycoprotein B (gB) and gH/gL (7,8). For epithelial cells, gH/gL and gB are important for EBV infection (4, 9, 10). Epithelial cells lack HLA class II expression; thus, gp42 cannot trigger EBV and cell fusion. Instead, gp42 inversely suppresses the infection (11), and an antibody against gp350 can enhance infections of CD21/CD35-negative epithelial cells (12). The gH/gL heterodimer is required for virus entry (4) and may be involved in binding (13), as well as fusion of EBV (14-17). However, the crystal structure of EBV gH/gL does not show any known fusion domain (18). It is now thought that gH/gL regulates the fusion function of gB (19). Binding of gH/gL to a subset of αv integrins (e.g., αvβ 5 , αvβ 6 , or αvβ 8 ) provides the initial trigger for gB-mediated fusion (16,20,21). However, E1D1(gH/gL) antibody or CL59(gH) antibody, with a different epitope, can impair epithelial cell infection (20,22). Thus, multiple gH/gL domains are critical to EBV infection, and gH/gL may interact with proteins in addition to integrins. Direct interaction of EBV gB amino acids 23-431 with neuropilin 1 (NRP1) and its associated tyrosine kinases is critical for EBV infection of nasopharyngeal ep...