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ABSTRACTOver 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4+ T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4+ T cells (but not CD8+ T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4+ T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4+ T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4+ T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).

Abstract Background Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. Methods Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. Results Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. Conclusion Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. Trial registration: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).

AimsEthanol infusion into the VOM (EIVOM) adjunctive to radiofrequency catheter ablation (RFCA) was a novel approach facilitating mitral isthmus (MIth) block for persistent atrial fibrillation (PeAF); However, there were remarkable disparities in its technical aspects. This study aimed to evaluate the impact of EIVOM technical aspects on acute MIth block.MethodsEighty consecutive patients (63 males, average age 66.4 ± 8.6 years) undergoing de novo PeAF ablation were assigned to different groups. The procedural parameters in “EIVOM first” (n = 13) or “RFCA first” (n = 13) as well as small dose ([SD], ≤4 ml, n = 26) or big dose ([BD], >4 ml, n = 54) approaches were analyzed to identify the predictors for acute MIth block.ResultsCompared with the “EIVOM first” approach, the “RFCA first” approach was associated with longer procedural and MIth ablation time (134 ± 27 min vs. 112 ± 17 min; 14.9 ± 5.5 min vs. 9.3 ± 5.1 min, both P < 0.05, respectively), but with comparable success of MIth block. The ethanol dose was 6.3 ± 1.5 ml in BD group vs. 3.1 ± 1.0 ml in SD group (P < 0.001) and was correlated significantly with the size of Δlow voltage area (r = 0.66, P < 0.001). The success of MIth block was 92.6% in BD group vs. 73.1% in SD group, P = 0.03. The ethanol dose >5.75 ml independently predicted successful MIth block (OR: 0.428, 95% CI: 0.219–0.839, P = 0.01).ConclusionsDespite the comparable effectiveness on MIth block, the “EIVOM first” approach was associated with shorter procedural and MIth ablation time than the “RFCA first” approach. The ethanol dose in EIVOM was an independent predictor for MIth block.

BackgroundCatheter ablation for parahisian ventricular arrhythmias (PHVA) is technically challenging and associated with increased risks of atrioventricular block (AVB). We developed a systemic mapping approach to improve the efficacy and safety of PHVA ablation.MethodsForty-three patients (29 males; average age 65.8 ± 10.5 years) with PHVAs were enrolled. A systemic mapping approach comprising differential electrocardiogram, sequential mapping, and ablation beneath/above the septal leaflet of the tricuspid valve (SLTV) and at the neighboring/contralateral regions (the aortic root and sub-aortic valve region) was applied for PHVA. The effectiveness and safety of this approach was evaluated at 1 year's follow-up.ResultsSequential ablation beneath the SLTV (B-SLTV) succeeded in 24 (66.7 %) of 36 with right PHVA and ablation above the SLTV succeeded in 6 of the remaining 12 with failed B-SLTV ablation. Target-His bundle (HB) distance > 4.5 mm significantly predicted successful right PHVA ablation (OR 1.703; 95% CI 1.084–2.676, P = 0.02). “Seeming” right PHVA by electrocardiogram in 4 and apparent left PHVA in 3 was successfully ablated at the sub-aortic parahisian region. At 1 year's follow-up, 27 (75%) of 36 patients with right PHVA and 6 (85.7%) of 7 patients with left PHVA were free of PHVA recurrence off anti-arrhythmic drugs. The total success rate was 76.7% by using the systemic mapping approach for PHVA. One patient with A-SLTV ablation underwent pacemaker implantation due to complete AVB.ConclusionsThe systemic mapping approach was effective and safe for treating PHVA. The target-HB distance was a significant predictor for right PHVA ablation.

Despite the good cooling effect of the contact-force porous catheter, the risk of steam pops (SP) remains one of the major concerns in high-power circumferential pulmonary vein isolation (CPVI). This study aimed to investigate the prevalence, predictors and possible mechanisms of SPs in CPVI. Patients experiencing SPs in de novo high-power CPVI were 1:3 matched by non-SP patients with gender, age (±5 years) and left atrial diameter (LAD) (±5 mm) to compare the ablation parameters of SP and non-SP lesions. Catheter tip displacement (Tipdisp) was compared between “edge-of-ridge” and “PV-side-of-ridge” placement at anterior and roof segments of the left pulmonary vein (PV). SPs occurred in 11 (1.57%) of 701 patients, including 6 at the antero-superior left PV, 2 at the roof, 1 at the postero-superior left PV, 1 at the bottom left PV and 1 at the antero-superior aspect of the right PV. There was significantly shorter RF delivery duration (13.9 ± 6.3 vs. 23.3 ± 6.0 s), greater Δimpedance (17.6 ± 6.7 vs. 6.7 ± 4.1 Ω) and lower ablation index (357.7 ± 68.8 vs. 430.2 ± 30.7) in SP patients than those in non-SP patients. Δimpedance >12 Ω during ablation could predict SP occurrence. Tipdisp was greater in “PV-side-of-ridge” than that in “edge-of -ridge” placement (3.2 ± 1.6 mm vs. 2.0 ± 0.8 mm) at antero-superior and roof segments of the left PV. The prevalence of SP was 1.57% in high-power CPVI procedures, with the most common site at the antero-superior segment of the left PV. Δimpedance was a significant predictor of SP occurrence. “PV-side-of-ridge” ablation at antero-superior and roof segments of left PV might predispose to SP occurrence due to excessive tissue coverage.

BackgroundCu-W composites are widely used in electric power, electronics, and plastic forming owing to the excellent electrical and thermal conductivities of copper combined with the outstanding strength and thermal properties of tungsten.PurposeThis study aims to investigate the extension of the solid solubility of the Cu-W immiscible system under high current pulsed electron beam (HCPEB) irradiation.MethodsFirst of all, the Cu-15W powder mixture was sintered by vacuum at 850 ℃ after ball milling for 5 h to prepare the Cu-W composites. After polishing, the Cu-W composites was exposed by a HOPE-1 type HCPEB device with 1, 5, 10 and 15 pulses, respectively. Then, Rigaku D/Max-2500/pc X-ray diffractometer (XRD) was used to analyze the phase constitutes of the milling powder, sintered samples and irradiated samples. The surface morphology was observed by JEOL JSM-7001F field emission scanning electron microscope (SEM). The energy dispersive spectrometer (EDS) in SEM was used for the examination of micro-region composition. Finally, the microstructures in the modified layer were characterized by JEOL-2100F transmission electron microscopy (TEM). The surface hardness of the sintered and irradiated samples with different pulses was measured using the HVS-1000 Vickers hardness tester.ResultsThe results reveal that Cu(W) solid solutions were formed during the process of ball milling, and the mass fraction of the solute element W in the Cu(W) solid solution reaches 0.88% after 5 h of ball milling. It was discovered that the solid solution undergoes exsolution reaction during heating using differential scanning calorimeter (DSC). The sintered sample surface was irradiated by a pulsed electron beam. The results demonstrate the formation of solid solution phase after HCPEB irradiation, whose solubility increases with the increase of the number of pulses. After 10 pulse irradiations, the mass percentage of solute element (W) in Cu(W) solid solutions reaches 1.63%. The surface hardness of irradiated samples increases significantly after HCPEB irradiation, and reaches 237.1 HV after 10-pulsed irradiation. Surface hardening is primarily caused by of solid solution strengthening and dispersion strengthening.ConclusionsThe present paper provides a meaningful instruction for preparing the immiscible alloy with high solid solubility and the excellent performance.

Parnassia wightiana Wall. ex Wight & Arn., a perennial herb, is an alpine plant distributed across three biodiversity hotspots in China. This species offers an excellent study system to analyze the distribution pattern and genetic structure of high mountainous plant populations. Three chloroplast DNA (cpDNA) regions (rpl32-trnL, trnL-F, and trnS-G) from 442 individuals of 39 populations and internal transcribed spacers (ITS) from 418 individuals of 38 populations were sequenced and analyzed. We identified a total of 26 haplotypes based on the concatenated sequences of cpDNA and a total of 36 based on ITS sequences. A hierarchical analysis of molecular variance indicated significant phylogeographic structure among populations. Mismatch analysis of multipeak and Tajima's D neutral test demonstrated Parnassia wightiana populations within China had not experienced abrupt expansion recently. The allopatric fragmentation resulted in the geographic isolation due to environmental heterogeneity, producing a high proportion of private haplotypes in the distribution of Parnassia wightiana within China. Key words: Parnassia wightiana Wall. ex Wight & Arn., cpDNA, ITS, genetic diversity, phylogeography, Introduction Climatic oscillations during the Cenozoic period, especially the Quaternary glacial and interglacial cycle, shaped the distribution of species (Hewitt 2004). Phylogeography is a discipline that deals with the spatial [...]