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Abstract Background High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. Methods From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator’s discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24–72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. Results All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). Conclusions Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. Trial registration Clinicaltrials.gov: NCT04408716. Graphical Abstract AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) has cured many patients with malignant hematologic diseases such as mixed phenotype acute leukemia (MPAL), while those relapsing after allo-HSCT still exhibit high mortality, poor prognosis, and no standard treatment modalities. It is necessary to explore more therapeutic modalities for patients with post-transplant relapse to obtain a better prognosis.Case presentationIn this case report, a young male with MPAL received allo-HSCT after reaching complete remission (CR) by induction chemotherapy. Unfortunately, relapse of both myeloid and T lineages occurred nine months later. After receiving demethylating chemotherapy, myeloid lineage measurable residual disease (MRD) turned negative. T-lineage MRD turned negative after CD7-targeted chimeric antigen receptor (CAR)-T cell therapy. The bone marrow remained MRD-negative for 4 months. This case preliminarily demonstrated a long-lasting CR with CD7-targeted CAR-T cell therapy, allowing a better prognosis.ConclusionDemethylating drugs combined with CD7-targeted CAR-T cell therapy is feasible in treating MPAL patients with relapse after transplantation, with good efficacy and safety, which will be a promising treatment option for MPAL.

ObjectiveTo systematically compare the bowel cleaning ability, patient tolerance and safety of oral sodium phosphate tablets (NaPTab) and oral polyethylene glycol electrolyte lavage solution (PEGL) to inform clinical decision making.MethodsPubMed, Embase, CBM, WanFang Data, CNKI, and VIP databases were searched for studies that used randomized controlled trials (RCTs) to compare the roles of NaPTab and PEGL in bowel preparation before colonoscopy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias in the included papers. A meta-analysis was performed using RevMan 5.3 software.ResultsA total of 13 RCTs were eligible for inclusion, including 2,773 patients (1,378 and 1,395 cases in the NaPTab and PEGL groups, respectively). Meta-analysis revealed no significant difference in the cleansing quality of the NaPTab and PEGL groups [RR 1.02, 95% CI (0.96–1.08), P = 0.46]. The incidence of nausea was lower in the NaPTab group than in the PEGL group [RR 0.67, 95% CI (0.58–0.76), p < 0.00001]. Patients rated the taste of NaPTab higher than PEGL [RR 1.33, 95% CI (1.26–1.40), P < 0.00001]. Willingness to repeat the treatment was also higher in the NaPTab group than in the PEGL group [RR 1.52, 95% CI (1.28–1.80), P < 0.00001]. Both serum potassium and serum calcium decreased in both groups after the preparation; however, meta-analysis revealed that both minerals decreased more in the NaPTab group than in the PEGL group [MD = 0.38, 95% CI (0.13–0.62), P = 0.006 for serum potassium and MD = 0.41, 95% CI (0.04–0.77), P = 0.03 for serum calcium]. Meanwhile, serum phosphorus increased in both groups after the preparation; however, levels increased more in the NaPTab group than in the PEGL group [MD 4.51, (95% CI 2.9–6.11), P < 0.00001].ConclusionsWhile NaP tablets and PEGL were shown to have a similar cleaning effect before colonoscopy, NaP tablets had improved patient tolerance. However, NaP tablets had a strong effect on serum potassium, calcium, and phosphorus levels. For patients with low potassium, low calcium, and renal insufficiency, NaP tablets should be prescribed with caution. For those at high-risk for acute phosphate nephropathy, NaP tablets should be avoided. Given the low number and quality of included studies, these conclusions will require additional verification by large high-quality studies.Systematic review registration10.37766/inplasy2023.5.0013, identifier: NPLASY202350013.

Generalized accelerated AOR (GAAOR) splitting iterative method for the generalized saddle point problems is proposed in this paper. The iterative scheme and the convergence of the GAAOR splitting method are researched. The eigenvalues distributions of its preconditioned matrix is discussed under {two different choices of the parameter matrix Q}. The resulting GAAOR preconditioner is used to precondition Krylov subspace method such as the restarted generalized minimal residual (GMRES) method for solving the equivalent formulation of the generalized saddle point problems. The theoretical results and effectiveness of the GAAOR splitting iterative method are supported by {some} numerical examples.

Objective To elucidate the ameliorative effect of AP39 on myocardial fibrosis in uremic rats and investigate its possible mechanism. Methods Forty SD male rats were randomly and equally divided into 4 groups: Sham group, uremic cardiomyopathy group (UCM group), AP39 intervention group (UCM+AP39 group) and AP39 control group (n=10). The rats in the UCM group and the UCM+AP39 group were treated with classical operation of 5/6 nephrectomy to establish the uremic cardiomyopathy model, and then the rats in the latter 2 groups were given intraperitoneal injection of AP39 (100 nmol/kg, once a day) for 4 weeks, while those of the Sham and model groups were intraperitoneally injected with the same amount of normal saline. Ultrasonic imaging platform was used to detect the value of left ventricular fractional shortening (LVFS) of rats in each group. Masson staining and immunohistochemical staining were performed respectively to observe collagen deposition and the expression of Collagen Ⅲ protein in the myocardial interstitial tissue of each group. Western blotting was adopted to determine the expression levels of PETN-induced putative kinase-1 (PINK1), Parkinson's disease protein (Parkin), autophagy-related gene-5 (Atg5), microtubule-associated protein-1 light chain-3 Ⅱ/Ⅰ(LCEⅡ/Ⅰ), Beclin1 and P62 (also called sequestosome, SQSTM1) in the myocardial tissue of each group. Results As compared with those in the Sham group, the rats in the UCM group had significantly decreased LVFS, increased collagen deposition content and Collagen Ⅲ protein level (P < 0.05), and disordered arrangement in myocardial tissue. The expression levels of PINK1, Parkin, Atg5, LC3Ⅱ/Ⅰand Beclin1 were significantly reduced, while the level of P62 was enhanced in the UCM group (P < 0.05). By contrast, the rats in the UCM+AP39 group had higher LVFS, lower collagen deposition content and Collagen Ⅲ protein level than those in the UCM group (P < 0.05), the expression levels of PINK1, Parkin, Atg5, LC3 Ⅱ/Ⅰ and Beclin1 were remarkably up-regulated, and the level of P62 down-regulated (P < 0.05). Conclusion AP39 can improve uremic myocardial fibrosis in rats, which may be related to the up-regulation of PINK1/Parkin-mediated mitophagy.

Abstract Background Mulberry leaf as a traditional Chinese medicine is able to treat obesity, diabetes, and dyslipidemia. It is well known that diabetes leads to intestinal microbiota dysbiosis. It is also recently discovered that liver glycogen structure is impaired in diabetic animals. Since mulberry leaves are able to improve the diabetic conditions through reducing blood glucose level, it would be interesting to investigate whether they have any positive effects on intestinal microbiota and liver glycogen structure. Methods In this study, we first determined the bioactive components of ethanol extract of mulberry leaves via high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). Murine animal models were divided into three groups, normal Sprague-Dawley (SD) rats, high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic rats, and HFD/STZ-induced rats administered with ethanol extract of mulberry leaves (200 mg/kg/day). Composition of intestinal microbiota was analyzed via metagenomics by sequencing the V3-V4 region of 16S rDNAs. Liver glycogen structure was characterized through size exclusion chromatography (SEC). Both Student’s t-test and Tukey’s test were used for statistical analysis. Results A group of type 2 diabetic rat models were successfully established. Intestinal microbiota analysis showed that ethanol extract of mulberry leaves could partially change intestinal microbiota back to normal conditions. In addition, liver glycogen was restored from fragile state to stable state through administration of ethanol extract of mulberry leaves. Conclusions This study confirms that the ethanol extract of mulberry leaves (MLE) ameliorates intestinal microbiota dysbiosis and strengthens liver glycogen fragility in diabetic rats. These finding can be helpful in discovering the novel therapeutic targets with the help of further investigations.

Objective To investigate the effects of dehydrocostuslactone treatment on the proliferation and apoptosis of human HepG2 cells and potential mechanisms. Methods HepG2 cells were divided into 6 groups incubated with different concentration of Dehydrocostuslactone. The cell proliferation was evaluated by MTT assays, and Hoechst 33258 fluorescence staining was conducted to observe apoptosis of cells subsequently.The expression of p-IκBα, IκBα, nuclear p65 and total p65 proteins in HepG2 cells were measured using Western blot. Results Compared with the control group, dehydrocostuslacton,in a dose dependent manner, significantly inhibited the proliferation of HepG2 cells with impressive profile of apoptosis (P＜0.05 or P＜0.01). Dehydrocostuslactone, at concentrations of 10, 20 and 30 μmol/L, resulted in a significantly decrease of p-IκBα and nuclear p65 expression (P＜0.05 or P＜0.01) and an increased IκBα expression (P＜0.05 or P＜0.01), whereas no marked effect on total p65 expression was observed. Conclusions Dehydrocostuslactone inhibits proliferation and promotes apoptosis of HepG2 cells, the mechanism may be explained by the down-regulation of NF-κB pathway in HepG2 cell.

Diabetes is a chronic endocrine metabolism disorder that leads to hyperglycaemia. As the most common diabetic type, type 2 diabetes mellitus accounts for 90% of all diabetic disease with a key feature of insulin resistance. Mulberry leaves are commonly used in traditional Chinese medicine, and many studies confirm that mulberry leaves have positive effects on alleviating the pathological conditions of type 2 diabetes. However, its anti-diabetic effects and active ingredients are not completely understood. Compared with time- and cost-consuming experiments, network pharmacology provided a convenient method to systematically investigate the interactions between compounds in mulberry leaves and diabetes-related genes. Although similar network pharmacological studies were performed for mulberry leaves, only compounds sourced from public database or volatile components in the mulberry leaves were examined. In this study, we initially analysed the bioactive compounds from ethanol extract of mulberry leaves via liquid chromatography coupled with mass spectrometry, which generated a total of 248 components. A total of 14 active components and 49 potentially functional compounds were identified from TCMSP and PharmMapper database, respectively, which worked on 37 target proteins directly involved in the pathogenesis of T2DM. Kaempferol was shown to be the most influential active compound while androgen receptor was most widely regulated by compounds in the ethanol extract of mulberry leaves. Moreover, protein–protein interaction and target-pathway network analysis revealed that AKT1 was most important in the 37 target proteins in terms of its functions in different pathways and interactions with other target proteins. Moreover, pathway analysis showed that ethanol extract of mulberry leaves alleviated type 2 diabetes mellitus through pathways such as TNF signaling pathway, NF-κB signaling pathway, and insulin resistance pathway. In sum, this study provided a complete overview of the working mechanisms for the ethanol extract of mulberry leaves, the results of which could be used as a practical guidance for further experimental investigation of the functions of mulberry leaves during the treatment of type 2 diabetes mellitus.

According to the sit-and-wait hypothesis, long-term environmental survival is positively correlated with increased bacterial pathogenicity because high durability reduces the dependence of transmission on host mobility. Many indirectly transmitted bacterial pathogens, such as Mycobacterium tuberculosis and Burkhoderia pseudomallei, have high durability in the external environment and are highly virulent. It is possible that abiotic stresses may activate certain pathways or the expressions of certain genes, which might contribute to bacterial durability and virulence, synergistically. Therefore, exploring how bacterial phenotypes change in response to environmental stresses is important for understanding their potentials in host infections. In this study, we investigated the effects of different concentrations of salt (sodium chloride, NaCl), on survival ability, phenotypes associated with virulence, and energy metabolism of the lab strain Escherichia coli BW25113. In particular, we investigated how NaCl concentrations influenced growth patterns, biofilm formation, oxidative stress resistance, and motile ability. In terms of energy metabolism that is central to bacterial survival, glucose consumption, glycogen accumulation, and trehalose content were measured in order to understand their roles in dealing with the fluctuation of osmolarity. According to the results, trehalose is preferred than glycogen at high NaCl concentration. In order to dissect the molecular mechanisms of NaCl effects on trehalose metabolism, we further checked how the impairment of trehalose synthesis pathway (otsBA operon) via single-gene mutants influenced E. coli durability and virulence under salt stress. After that, we compared the transcriptomes of E. coli cultured at different NaCl concentrations, through which differentially expressed genes (DEGs) and differential pathways with statistical significance were identified, which provided molecular insights into E. coli responses to NaCl concentrations. In sum, this study explored the in vitro effects of NaCl concentrations on E. coli from a variety of aspects and aimed to facilitate our understanding of bacterial physiological changes under salt stress, which might help clarify the linkages between bacterial durability and virulence outside hosts under environmental stresses.

Tectonically deformed coal (TDC) is closely related to gas outbursts. Since TDC exploration is an essential objective for coalfield exploration, it is of great significance to study the petrophysical properties of TDCs and explore their differences. This study collected 17 TDCs and undeformed coal samples from the Huaibei coalfield and ultrasonically tested their petrophysical parameters, including densities, P- and S-wave velocities, and their derived petrophysical parameters (VP/VS ratio, P- and S-wave impedances). Undeformed coal and TDCs with different deformation types (brittle, shear, and plastic deformations) show significant differences in their petrophysical parameters, and cross-plot analysis can directly differentiate them. As with traditional geological methods, acoustically measured petrophysical parameters are good indicators to determine the type of coal deformation. However, the TDCs with the same deformation type have similar petrophysical parameters; it is not easy to distinguish them directly. Instead, the proposed method incorporating principal component analysis and clustering can accurately distinguish up to five classes of TDCs. Different types of tectonic deformation environments and their intensities are highly correlated with the clustering results. This paper also provides essential petrophysical parameters for undeformed coal and TDCs in the Huaibei coalfield, and these parameters can help interpret undeformed coal and TDCs using wireline logs and seismic data. [ABSTRACT FROM AUTHOR]