Multi-omics reveals Dengzhan Shengmai formulation ameliorates cognitive impairments in D-galactose-induced aging mouse model by regulating CXCL12/CXCR4 and gut microbiota.

Dengzhan Shengmai (DZSM), a traditional Chinese medicine formulation, has been administered extensively to elderly individuals with cognitive impairment (CI). However, the underlying mechanisms by which Dengzhan Shengmai improves cognitive impairment remains unknown. This study aimed to elucidate the underlying mechanism of the effect of Dengzhan Shengmai on aging-associated cognitive impairment via a comprehensive combination of transcriptomics and microbiota assessment. Dengzhan Shengmai was orally administered to a D-galactose-induced aging mouse model, and evaluation with an open field task (OFT), Morris water maze (MWM), and histopathological staining was performed. Transcriptomics and 16S rDNA sequencing were applied to elucidate the mechanism of Dengzhan Shengmai in alleviating cognitive deficits, and enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (PCR), and immunofluorescence were employed to verify the results. The results first confirmed the therapeutic effects of Dengzhan Shengmai against cognitive defects; specifically, Dengzhan Shengmai improved learning and impairment, suppressed neuro loss, and increased Nissl body morphology repair. Comprehensive integrated transcriptomics and microbiota analysis indicated that chemokine CXC motif receptor 4 (CXCR4) and its ligand CXC chemokine ligand 12 (CXCL12) were targets for improving cognitive impairments with Dengzhan Shengmai and also indirectly suppressed the intestinal flora composition. Furthermore, in vivo results confirmed that Dengzhan Shengmai suppressed the expression of CXC motif receptor 4, CXC chemokine ligand 12, and inflammatory cytokines. This suggested that Dengzhan Shengmai inhibited CXC chemokine ligand 12/CXC motif receptor 4 expression and modulated intestinal microbiome composition by influencing inflammatory factors. Thus, Dengzhan Shengmai improves aging-related cognitive impairment effects via decreased CXC chemokine ligand 12/CXC motif receptor 4 and inflammatory factor modulation to improve gut microbiota composition.

Hydrogen phosphates play a critical structural role in amorphous calcium phosphates.

Amorphous calcium phosphate (ACP) is an intriguing mineral phase of calcium phosphate in its own right, in addition to its relevance in biomineralization. We hereby demonstrate that ACPs prepared by different synthetic routes such as the crosslinking of inorganic oligomers and polymer-induced liquid precursors have distinctive relative compositions of orthophosphate and hydrogen phosphate, and the extent of their hydrogen bonding with water. For all the ACPs or ACP-derived materials studied in this work, the species of hydrogen phosphate is the most important structural element. Depending on the synthetic pathways, orthophosphate and water, as well as their associated hydrogen bonds, may also play a role in the structural formation of ACPs.

Elevated N-terminal pro C-type natriuretic peptide is associated with mortality in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR). METHODS: A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1-4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis. RESULTS: A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05-1.12, P < 0.001). Elevated NT-proCNP was associated with a higher risk of cardiovascular mortality (HR 1.02, 95% CI 1.00-1.03, P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00-1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) < 50% [(Area under the curve (AUC)-values of 0.79 (0.69; 0.87) vs. 0.59 (0.48; 0.69), P = 0.0453]. CONCLUSIONS: NT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF < 50%. Trial registration NCT02803294, 16/06/2016.

Generalized Oscillator Strengths for the Valence Shell Excitations in Carbon Tetrachloride Studied by Fast Electron Impact.

A joint experimental and theoretical investigation of the valence shell excitations of carbon tetrachloride has been performed by fast electron scattering and time dependent density functional theory calculations. At a collision energy of 1.5 keV and an energy resolution of about 70 meV, the dipole-forbidden transition of a1σ* ← 2t1 has been clearly observed at large momentum transfers, and its excitation energy of 6.15 eV and line width of 0.72 eV have been determined. Two new features are also recognized at 9.97 and 10.26 eV. The generalized oscillator strengths of the excited states at 5-11.3 eV have been determined from the measured spectra. The calculated generalized oscillator strength of the a1σ* ← 2t1 transition with the vibronic effect shows better agreement with the experiment, and the vibronic effect also accounts for its nonzero intensity at zero squared momentum transfer. The optical oscillator strengths of the valence shell excitations have also been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The integral cross sections have been systematically determined from the threshold to 5000 eV by means of the BE-scaling method. The present oscillator strengths and cross sections provide the fundamental data of carbon tetrachloride and have important applications in photochemical modeling for atmospheric physics.

The Study of the Low-Lying Valence-Shell Excitations of Hydrogen Sulfide by Fast Electron Impact.

The valence-shell excitations of hydrogen sulfide have been studied by fast electron impact at a collision energy of 1.5 keV and an energy resolution of about 70 meV. By analyzing the variations of intensity and shape of the feature in the range of 5.0-7.5 eV at different scattering angles, the excitation energy of 5.85 ± 0.01 eV and the line width of 0.80 ± 0.01 eV of the 3b21A2 state have been determined. The generalized oscillator strengths of the valence-shell excitations in the energy range of 5.0-9.2 eV of hydrogen sulfide have been determined from the measured spectra. The corresponding optical oscillator strengths have been obtained by extrapolating the generalized oscillator strengths to the limit of zero squared momentum transfer. The integral cross sections have also been systematically determined from the threshold to 5000 eV by means of the BE-scaling method. The presently obtained oscillator strengths and integral cross sections have significant applications in the studies of planetary atmospheres and interstellar gases.

The first two cases of transcatheter mitral valve repair with ARTO system in Asia.

BACKGROUND: MAVERIC (Mitral Valve Repair Clinical Trial) validates the safety and efficacy of the ARTO system. We here report the first two successful cases of utilizing the ARTO system in patients with symptomatic heart failure (HF) with functional mitral regurgitation (FMR) in Asia. METHODS: Two patients, aged 70 and 63, had severe HF with FMR. Transesophageal echocardiography confirmed that the left ventricular ejection fractions were less than 50% with severe mitral regurgitation (MR) in both patients. Optimizing drug treatment could not mitigate their symptoms. Therefore, we used the ARTO system to repair the mitral valve for these patients on March 5 and 6, 2019, respectively. RESULTS: Mitral valve repairs using the ARTO system were successfully performed under general anaesthesia for these two patients. MR was decreased immediately after the procedures in both patients. The 30-day and 3-month transthoracic echocardiography (TTE) revealed a moderate to severe MR in both patients, and the New York Heart Association (NYHA) scales were also partially improved. CONCLUSION: The first two cases in Asia indicate that the ARTO system is feasible for patients with heart failure with FMR, and the patient selection appears to be crucial.

Ascending aortic dilatation rate after transcatheter aortic valve replacement in patients with bicuspid and tricuspid aortic stenosis: A multidetector computed tomography follow-up study.

BACKGROUND: Current data is lacking about the progression of ascending aortic dilatation after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). This study aims to assess the ascending aortic dilatation rate (mm/year) after TAVR in patients with BAV versus TAV using a multidetector computed tomography (MDCT) follow-up and to determine the predictors of ascending aortic dilatation rate. METHODS: Severe AS patients undergoing TAVR from March 2013 to March 2018 at our center with MDCT follow-ups were included. BAV and TAV were identified using baseline MDCT. Baseline and follow-up MDCT images were analyzed, and the diameters of ascending aorta were measured. Study end point is ascending aortic dilatation rate (mm/year). Furthermore, factors predicting ascending aortic dilatation rate were also investigated. RESULTS: Two hundred and eight patients were included, comprised of 86 BAV and 122 TAV patients. Five, 4, 3, 2, and 1-year MDCT follow-ups were achieved in 7, 9, 30, 46, and 116 patients. The ascending aortic diameter was significantly increased after TAVR in both BAV group (43.7±4.4 mm vs. 44.0±4.5 mm; P<0.001) and TAV group (39.1±4.8 mm vs. 39.7±5.1 mm; P<0.001). However, no difference of ascending aortic dilatation rate was found between BAV and TAV group (0.2±0.8 mm/year vs. 0.3±0.8 mm/year, P=0.592). Multivariate linear regression revealed paravalvular leakage (PVL) grade was independently associated with ascending aortic dilatation rate in the whole population and BAV group, but not TAV group. No aortic events occurred during follow-ups. CONCLUSION: Ascending aortic size continues to grow after TAVR in BAV patients, but the dilatation rate is mild and comparable to that of TAV patients. PVL grade is associated with ascending aortic dilatation rate in BAV patients post-TAVR.

The first four cases of successful NeoChord procedure in mainland China.

BACKGROUND: Transapical off-pump NeoChord procedure is a novel minimally invasive surgical repair of degenerative mitral regurgitation (MR). Here, we report the first four cases of NeoChord procedure in patients with mitral valve prolapse in mainland China. METHODS: Four patients, aged 86, 84, 80 and 60 years, with severe MR due to posterior middle scallop prolapse (P2), underwent transapical off-pump artificial chordae implantation on April 9 and 10, 2019. The procedure was performed by left mini-thoracotomy under general anaesthesia and guided by 2D and 3D dimensional transoesophageal echocardiography (TEE). RESULTS: Mitral valve repair via NeoChord procedure was successfully performed with implantation of 3 artificial chordae in the first patient and 3, 2, and 3 artificial chordae in the following patients, respectively. Intraoperative TEE and pre-discharge transthoracic echocardiography (TTE) showed only mild to moderate MR of these four patients and no postoperative complications were noted. There were no changes of TTE finding between one-month follow-up and pre-discharge. CONCLUSION: The successful NeoChord procedures in four Chinese indicate that the valve repair using the NeoChord system for Chinese population is feasible.

Effect of corticosteroids on atrial fibrillation after catheter ablation: a meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to explore the effect of corticosteroids on atrial fibrillation (AF) following catheter ablation. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for published articles describing the effect of corticosteroids in preventing AF recurrence after catheter ablation. Data on study and patient were extracted. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by use of a random-effect model, and P values of <0.05 were considered significant. RESULTS: Two randomized controlled trials (RCTs) and three cohort studies involving 846 patients were included in this meta-analysis. Within one month of catheter ablation, corticosteroid use was associated with a declined risk of recurrence of AF in RCT (RR 0.57, 95% CI 0.39 to 0.85, P=0.005), but without significant effect in cohort studies (RR 1.01, 95% CI 0.79 to 1.30, P=0.94). After three months of catheter ablation, corticosteroids did not have a significant effect in the prevention of late recurrence of AF in either RCT (RR 0.78, 95% CI 0.38 to 1.59, P=0.49) or cohort studies (RR 0.96, 95% CI 0.70 to 1.31, P=0.78). CONCLUSIONS: Our meta-analysis suggested that periprocedural administration of corticosteroids of catheter ablation was associated with reduction of early but not late recurrence of AF.

First-in-man implantation of the retrievable and repositionable VenusA-Plus valve.

BACKGROUND: No retrievable and repositionable second generation transcatheter aortic valve is available in China. Here, we report the first-in-man implantation of the retrievable and repositionable VenusA-Plus valve. METHODS: A 76-year-old patient with symptomatic severe aortic stenosis and high surgical risk (STS 13.8%) was recommended for transcatheter aortic valve replacement (TAVR) by heart valve team. Type 0 bicuspid aortic valve with asymmetric calcification was identified by dual source computed tomography, and the unfavorable anatomies increased the possibility of malposition and paravalvular leakage during TAVR. Therefore, we used the retrievable and repositionable VenusA-Plus valve for the patient. RESULTS: Transfemoral TAVR was performed under local anesthesia with sedation, and a 26mm VenusA-Plus valve was successfully implanted. No transvalvular pressure gradient and trace paravalvular leakage were found. CONCLUSION: The successful first-in-man implantation indicates the retrievable and repositionable VenusA-Plus valve is feasible in complicated TAVR cases such as bicuspid aortic valve.

[Association of chemokines and their receptors genes polymorphisms with risk of myocardial infarction].

OBJECTIVE: To assess the association of variations in chemokines (CCL5, CCL2), chemokine receptor (CCR5 and CCR2) genes with susceptibility to myocardial infarction (MI) through a case-control study. METHODS: Genotypes of patients with MI (n = 634) were compared with those of controls (n = 601). Genetic polymorphisms of CCL5 rs2107538 (-403G > A), CCL2 rs1024611 (-2518A > G), CCR5 rs333 ( δ 32 ins or del) and CCR2 rs1799864 (190G > A) of 1235 individuals were determined with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Particular genotypes were confirmed with DNA sequencing. RESULTS: No subject was found to carry the CCR5 - δ 32 allele. No association was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For CCL5 rs2107538 polymorphism, the A allele has occurred at a higher frequency in MI patients than controls, and its AA genotype has been associated with a significantly increased risk of MI independent of conventional risk factors (OR = 3.346, 95%CI = 1.938-5.775, P < 0.01, AA vs. GG). Further analysis indicated that MI patients had significantly more A-403 - A-2518 haplotype (CCL5 -403G > A and CCL2 -2518A > G, 21.8% vs. 26.6%, OR = 1.229, 95%CI = 1.012-1.493, P = 0.038) and AA or AA genotype (CCL5 -403G > A - CCL2 -2518A > G, 5.0% vs. 12.1%, OR = 3.245, 95%CI = 1.780-5.914, P < 0.01). CONCLUSION: Although our data dose not support an association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms and MI, genetic variation in CCL5 gene may still be a useful marker for assessing susceptibility to MI in ethnic Han Chinese population.