Predictive Value of NT-proBNP for New-onset Atrial Fibrillation in the Acute Phase of Myocardial Infarction.

Objective: The objective of this study was to assess the predictive value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels on admission and new-onset atrial fibrillation (AF) in patients with acute myocardial infarction (AMI). Methods: In this study, a retrospective cohort study design scheme was used to include a total of 291 consecutive patients who were hospitalized for AMI from July 2019 to May 2020, of whom 36 (12.4%) developed new-onset atrial fibrillation (AF) during their hospitalization, which was classified as the AF group, and the rest of the patients were in the non-AF group. The impact of NT-pro-BNP on new-onset atrial fibrillation was investigated using the general data, laboratory tests, cardiac ultrasonography, and coronary angiography results of the two groups. Logistic regression analysis was employed to investigate the effect of NT-pro-BNP on new-onset atrial fibrillation. Additionally, we analyzed the significance of NT-pro-BNP in predicting new-onset AF in AMI patients using the the area under the AUC. Results: Univariate analysis indicated that patients in the AF group had significantly higher (P < .05) age, leukocyte count on admission, high-sensitivity C-reactive protein (hs-CRP), blood creatinine, uric acid, NT-pro-BNP, and left ventricular end-diastolic internal diameter (LVED) than those in the non-AF group. Patients in the AF group had lower blood pressure and left ventricular ejection fraction compared with the non-AF group. Logistic multifactorial regression analysis indicated that NT-pro-BNP was an independent risk factor for new-onset AF in patients with AMI (OR=2.752, 95% CI 1.352-5.602, P = .005). The area under the AUC was 0.747 (95% CI 0.655-0.84; P = .001), with a sensitivity of 64%, a specificity of 78%, and a Jordon's index of 0.458. This corresponds to an optimal cutoff value of 5374 pg/ml, suggesting that NT-pro-BNP performs well in predicting new-onset atrial fibrillation. Conclusion: NT-pro-BNP on admission can be a useful predictor of whether new-onset atrial fibrillation occurs in patients with AMI, with good predictive value. This finding helps better to meet patients' diagnostic and therapeutic needs and provides useful clinical guidance to improve the management and prognosis of AMI patients.

The deubiquitinase USP44 promotes Treg function during inflammation by preventing FOXP3 degradation.

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-ß induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy.

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Computer-Aided Design/Computer-Aided Manufacture (CAD/CAM)-Fabricated Partial Crowns.

BACKGROUND We aimed to investigate the clinical effects of resin nanoceramic (RNC) computer-aided design/computer-aided manufacture (CAD/CAM) partial crowns on posterior teeth after root canal treatment over a 3-year period. MATERIAL AND METHODS A total of 132 posterior teeth restored with CAD/CAM partial crowns were placed in 128 patients. The observation group (n=66) was restored with RNC restorations, while the control group received lithium disilicate-based glass ceramic (LDGC) CAD restorations. Using Federation dentaire internationale (FDI) World Dental Federation clinical criteria, 2 calibrated evaluators examined the performance of the restorations at baseline, 6, 12, 18, 24, and 36 months. The Kaplan-Meier method and the log-rank test were adopted to analyze the survival rate. The influence of potential risk factors on the main pattern of failure was studied by univariate Cox regression analysis (alpha=0.05). RESULTS At the 3-year followup, the survival rate of the partial crowns was 83.1% in the RNC group, and 93.5% in the LDGC group (P=0.061). Failures were caused by debonding (66.7%), restoration fracture (26.6%), and tooth fracture (6.7%). No significant differences were found between the 2 materials at 36 months, except for the parameters of "surface luster" (P=0.002) and "occlusal contour and wear" (P=0.009). The RNC group was significantly more likely to debond than the LDGC group (hazard ratio=9.22 [1.17,72.74], P=0.01). CONCLUSIONS RNC CAD/CAM-fabricated partial crowns are a potential clinical alternative for endodontically treated posterior teeth, with a survival rate of 83.1% at the 3-year followup. The main pattern of failure was debonding, which might be influenced by surface pretreatment of the RNC material.

A Cross-Sectional Observational Study to Compare the Role of Ultrasound with Mammography in Women Identified at High Risk for Breast Cancer in a Population in China.

BACKGROUND Currently, there is no national breast cancer screening program in China. In countries that have screening programs, screening mammography is used. This study aimed to compare the imaging parameters and diagnostic findings between ultrasound and mammography in women at high risk who had a histologically confirmed diagnosis of breast cancer in a population in China. MATERIAL AND METHODS A cross-sectional observational study included 1,687 women with a risk score of ≥30, according to the cancer risk assessment model, who underwent breast ultrasound and mammography. Women who had a Breast Imaging-Reporting and Data System (BI-RADS) score of 4 or 5 were identified, and 155 women had breast cancer confirmed by breast biopsy and histology. The ultrasound and mammography findings were evaluated and compared. RESULTS Breast ultrasound resulted in significantly fewer inconclusive results (BI-RADS score, 0), when compared with mammography (p=0.046). In cases with a histologically confirmed diagnosis of breast cancer (BI-RADS score, 4), the diagnostic sensitivity of breast ultrasound and mammography were 0.989 and 0.859, respectively. In cases with a histologically confirmed diagnosis of breast cancer (BI-RADS score, 5), the diagnostic sensitivity of breast ultrasound and mammography were 1.000 and 0.984, respectively. In cases with a histologically confirmed diagnosis of benign breast lesions (BI-RADS score, 2), there was no significant difference between breast ultrasound and mammography. CONCLUSIONS In a population of women in China, breast ultrasound was a more sensitive diagnostic imaging method for women with high risk BI-RADS 4 and 5 breast lesions.

The Association Between the Use of Antiarrhythmic Drugs in Non-Valvular Atrial Fibrillation and Patient Prognosis Using Data from the China Atrial Fibrillation (China-AF) Registry.

BACKGROUND Results of the landmark Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial comparing rhythm control and rate control strategies has led to dramatic changes in the pharmacological management of non-valvular atrial fibrillation (NVAF) patients. We sought to investigate the effect of antiarrhythmic drugs (AADs) on the clinical outcomes of NVAF patients using "real-world" data from China. MATERIAL AND METHODS We evaluated the association between AAD usage and clinical outcomes using clinical data of 8161 NVAF patients who were AAD-naive before enrollment in the China Atrial Fibrillation Registry, recruited between August 2011 and February 2017. The primary outcome was all-cause mortality. RESULTS Compared with 6167 patients who never used any AADs, 1994 patients in the AAD group had lower incidence (per 100 person-years) of all-cause mortality (1.44 versus 3.91), cardiovascular death (0.45 versus 2.31), ischemic stroke (1.36 versus 2.03), and cardiovascular hospitalization (9.83 versus 10.22) over a mean follow-up duration of 316.7±90.4 days. After adjusting for potential confounders, AAD usage was associated with a lower risk of all-cause mortality [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.31-0.81] and decreased risk of cardiovascular death (HR: 0.30, 95% CI: 0.13-0.68). Subgroup analysis revealed AAD was associated with higher risk of cardiovascular hospitalization among female patients. CONCLUSIONS AAD usage was associated with lower risk of 1-year all-cause mortality and cardiovascular death in "real-world" patients with NVAF.

Sex Differences in Presentation, Quality of Life, and Treatment in Chinese Atrial Fibrillation Patients: Insights from the China Atrial Fibrillation Registry Study.

BACKGROUND There is a growing recognition of sex-related disparities in atrial fibrillation (AF). However, limited data is available in Chinese AF patients. MATERIAL AND METHODS We compared symptoms, quality of life (QoL), and treatment of AF according to sex from the China AF Registry study. RESULTS We studied 14 723 patients with non-valvular AF, of whom 5645 patients (38.3%) were female. Women were older than men (67.5±10.6 vs. 62.2±12.2). Compared to men, women had more comorbidities and a higher proportion of CHA2DS2-VASC score ≥2. Women with AF experienced more severe or disabling symptoms than men (33.7% vs. 22.9% in age <75 group; 40.3% vs. 28.7% in age ≥75 group; both P<0.0001). After multivariate analysis, women with AF still had lower QoL (OR 0.69; 95%CI, 0.63-0.76; P<0.0001). Women tended to have lower rates of ablation and rhythm-control drug use in those aged <75 years. Oral anticoagulant use was low and had no sex difference in AF patients with a CHA2DS2-VASC score ≥2. CONCLUSIONS In Chinese AF patients, women were older and more symptomatic, and had worse QoL. Despite all these differences, women tended to receive less rhythm-control treatment in those aged <75 years. Oral anticoagulant was substantially underused in high stroke risk patients, regardless of sex.

Dynamic changes in miR-124 levels in patients with acute cerebral infarction.

OBJECTIVE: To investigate the changes in serum miR-124 levels in patients with acute cerebral infarction (ACI) and elucidate the underlying mechanism by a dynamic monitor. METHODS: Fifty-four patients with ACI and 51 healthy controls were included in our study. Baseline characteristics and blood samples were collected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the serum miR-124 levels. The dual-luciferase reporter assay was used to evaluate the effect of miR-124 on iASPP, a protein that inhibits apoptosis stimulating proteins in the p53 family. RESULTS: Compared with normal controls, the miR-124 levels in the ACI group rapidly decreased at phase 1 (within 24 h after ischemia) (p < 0.001) and then gradually increased at phase 2 (48 ∼ 72 h after ischemia) (p < 0.001) and phase 3 (the 7th day after ischemia) (p < 0.001). The dual-luciferase reporter assay showed that miR-124 down-regulates iASPP expression in 293T cells. CONCLUSION: The miR-124 levels are down-regulated in ACI patients. The dynamic changes of miR-124 might provide a possible method for the detection of ischemic stroke. Highlights The difference in miR-124 expression levels between ACI patients and normal controls. Dynamic changes of miR-124 expression levels in ACI patients. The down-regulation of miR-124 upon iASPP expression.

Long non-coding RNA RMST silencing protects against middle cerebral artery occlusion (MCAO)-induced ischemic stroke.

Long non-coding RNAs (lncRNAs) have emerged as major regulators in neurological diseases, and clarifying their roles in cerebral ischemic injury may provide novel targets for treating ischemic stroke. In this study, we mainly studied the role of lncRNA-RMST in middle cerebral artery occlusion (MCAO)-induced mouse brain injury. We showed that RMST expression level was significantly up-regulated in oxygen-glucose deprivation (OGD)-treated primary hippocampal neuron, MCAO-induced injured brain, and the plasma of patients with ischemic stroke. RMST silencing protected against MCAO-induced ischemic brain injury in vivo and OGD-induced primary hippocampal neuron injury in vitro. Intracerebroventricular injection of RMST shRNA significantly decreased brain RMST expression, reduced brain infarct size, and improved neurological function. Collectively, this study provides evidence that lncRNA is involved in the pathogenesis of ischemic brain injury, and suggests a promising approach of RMST inhibition in treating ischemic stroke.

Intratracheal administration of adipose derived mesenchymal stem cells alleviates chronic asthma in a mouse model.

BACKGROUND: Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model. METHODS: Murine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR. RESULTS: The mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1ß (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ. CONCLUSIONS: Intratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs.

Prospects of Contrast-Enhanced Ultrasonography for the Diagnosis of Peripheral Arterial Disease: A Meta-analysis.

OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) is a modern diagnostic method that can also be used to study microperfusion. This study compared the time to peak intensity measured by CEUS in patients with peripheral arterial disease (PAD) and healthy control participants. METHODS: After a comprehensive literature search in multiple electronic databases and study selection, a random-effect meta-analysis was performed to compare the time to peak intensity measured by CEUS in patients with PAD and healthy controls, which followed meta-regression analyses for identification of factors affecting the outcomes. RESULTS: Fourteen studies (data for 322 patients with PAD and 314 healthy individuals) were used for the meta-analysis. The age of this sample of patients with PAD was 64.92 (95% confidence interval, 62.53, 67.31) years, and that of the healthy controls was 55.32 (51.67, 58.98) years. The times to peak intensity were 18.55 (15.62, 21.48) seconds in healthy controls, 33.40 (27.65, 39.15) seconds in patients with PAD, and 76.22 (36.23, 116.22) seconds in patients with PAD and diabetes mellitus. The difference between patients with PAD and healthy controls in the time to peak intensity was statistically significant (mean difference, 24.80 [10.16, 39.44] seconds; P < .00009). The ABI was not significantly associated with the time to peak intensity in patients with PAD. Age and sex were also not significantly associated with the time to peak intensity. CONCLUSIONS: Contrast-enhanced ultrasonography is a valuable tool for the diagnosis of PAD based on its ability to differentiate the time to peak intensity between patients with PAD and healthy individuals, but little data are yet available to assess its diagnostic ability in clinical practice.

[Study of a CADASIL family with migraine as the presenting symptom].

OBJECTIVE: To analyze the clinical features and genetic cause for a family affected with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: Clinical manifestations, neuroimaging, and genetic analysis were performed. RESULTS: The main clinical features have included stroke, emotional disturbance and history of migraine without progressive memory impairment. A positive family history was confirmed. Cranial MRI has revealed multi-infarct lesions and white matter hyperintensity involving bilateral basal ganglia, subcortex and brain stem. All such features were in keeping with the diagnosis of CADASIL. A rare 2182C>T mutation in exon 14 of the NOTCH3 gene was identified in all available cases. CONCLUSION: Both clinical and molecular features suggested that the family has been affected with CADASIL.

Identification of the E3 deubiquitinase ubiquitin-specific peptidase 21 (USP21) as a positive regulator of the transcription factor GATA3.

The expression of the transcription factor GATA3 in FOXP3(+) regulatory T (Treg) cells is crucial for their physiological function in limiting inflammatory responses. Although other studies have shown how T cell receptor (TcR) signals induce the up-regulation of GATA3 expression in Treg cells, the underlying mechanism that maintains GATA3 expression in Treg cells remains unclear. Here, we show how USP21 interacts with and stabilizes GATA3 by mediating its deubiquitination. In a T cell line model, we found that TcR stimulation promoted USP21 expression, which was further up-regulated in the presence of FOXP3. The USP21 mutant C221A reduced its capacity to stabilize GATA3 expression, and its knockdown led to the down-regulation of GATA3 protein expression in Treg cells. Furthermore, we found that FOXP3 could directly bind to the USP21 gene promoter and activated its transcription upon TcR stimulation. Finally, USP21, GATA3, and FOXP3 were found up-regulated in Treg cells that were isolated from asthmatic subjects. In summary, we have identified a USP21-mediated pathway that promotes GATA3 stabilization and expression at the post-translational level. We propose that this pathway forms an important signaling loop that stabilizes the expression of GATA3 in Treg cells.

Serum biomarkers in patients with drug-resistant epilepsy: a proteomics-based analysis.

Objective: To investigate the serum biomarkers in patients with drug-resistant epilepsy (DRE). Methods: A total of 9 DRE patients and 9 controls were enrolled. Serum from DRE patients was prospectively collected and analyzed for potential serum biomarkers using TMT18-labeled proteomics. After fine quality control, bioinformatics analysis was conducted to find differentially expressed proteins. Pathway enrichment analysis identified some biological features shared by differential proteins. Protein-protein interaction (PPI) network analysis was further performed to discover the core proteins. Results: A total of 117 serum differential proteins were found in our study, of which 44 were revised upwards and 73 downwards. The up-regulated proteins mainly include UGGT2, PDIA4, SEMG1, KIAA1191, CCT7 etc. and the down-regulated proteins mainly include ROR1, NIF3L1, ITIH4, CFP, COL11A2 etc. Pathway enrichment analysis identified that the upregulated proteins were mainly enriched in processes such as immune response, extracellular exosome, serine-type endopeptidase activity and complement and coagulation cascades, and the down-regulated proteins were enriched in signal transduction, extracellular exosome, zinc/calcium ion binding and metabolic pathways. PPI network analysis revealed that the core proteins nodes include PRDX6, CAT, PRDX2, SOD1, PARK7, GSR, TXN, ANXA1, HINT1, and S100A8 etc. Conclusion: The discovery of these differential proteins enriched our understanding of serum biomarkers in patients with DRE and potentially provides guidance for future targeted therapy.

[Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in paratracheal mediastinal lesions].

OBJECTIVE: To explore the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing mediastinal lesions. METHODS: A total of 264 patients with mediastinal lesions on chest CT at Provincial Hospital Affiliated to Shandong University between January 2010 and April 2012 were retrospectively enrolled. Their cytopathological results were difficult to be assessed by conventional bronchoscopy. There were 222 cases whose lymph nodes long axis was >1.5 cm. Among them, 174 cases underwent TBNA alone (group A) and the other 48 cases EBUS-TBNA alone (group B). The remaining 42 cases whose lymph nodes long axis was <1.5 cm belonged to group C and underwent TBNA (group C1) and EBUS-TBNA (group C2) sequentially as a combined procedure. The associations of pathologic examinations, diagnostic positive rate and complications were analyzed. RESULTS: Among 174 cases in group A, 154 cases were diagnosed with a positive diagnostic rate of 88.5%. There were 135 malignant lesions while 19 cases were diagnosed with benign diseases and 5 cases had accidental vascular injury. Among 48 cases in group B, 45 cases were diagnosed with a positive diagnostic rate of 93.8%. There were 33 malignant lesions while 12 cases were diagnosed with benign diseases. Among 42 patients in group C1, 31 cases were diagnosed by TBNA with a positive diagnostic rate of 73.8%. There were 23 malignant lesions while 8 cases were diagnosed with benign diseases and 2 cases had accidental vascular injury. Among 42 patients in group C2, 39 cases were diagnosed with a positive diagnostic rate of 92.8%. There were 30 malignant lesions while 9 cases had benign diseases. No difference existed in diagnostic positive rate between groups A and B (χ(2) = 0.621, P = 0.431) while the diagnostic positive rate in group A was much higher than group C1 (χ(2) = 5.945, P = 0.015). The difference between groups B and C2 was insignificant (χ(2) = 0.065, P = 0.320) while there was significant difference between groups C1 and C2 (χ(2) = 5.486, P = 0.019). CONCLUSION: With a low complication rate, EBUS-TBNA can yield a higher diagnostic positive rate in diagnosing small mediastinal diseases than conventional TBNA.

A comparison of Doppler measures of ovarian blood flow between women with and without ovarian dysfunction and correlations of Doppler indices with ovarian dysfunction markers: a meta-analysis.

Background: Doppler ultrasonography is used to study ovarian vascular characteristics. However, the outcomes are reported with a considerable variability in literature. Here we review the differences in Doppler ultrasound-measured ovarian blood flow indices between women with and without ovarian dysfunction and seeks correlations between Doppler measures and ovarian markers. Methods: A literature search was conducted in electronic databases (Google Scholar, Ovid, PubMed, Science Direct, and Springer) to identify studies that used Doppler for ovarian blood flow examination and reported Doppler measures in women with and without ovarian dysfunction and/or the correlations between wDoppler indices and markers of ovarian dysfunction. After quality assessment of included studies, a meta-analysis of weighted mean differences (WMDs) between women with and without ovarian dysfunction in vascularization index (VI), flow index (FI), vascularization flow index (VFI), pulsatility index (PI) and resistance index (RI) was performed. Correlation coefficients between Doppler indices and markers of ovarian dysfunction were pooled to achieve overall estimates. Results: A total of 27 studies [2,377 women with ovarian dysfunction and 308 controls; age 27.7 years, 95% confidence interval (CI): 26.4 to 29.1] were included. These studies were of moderate quality. The VI (WMD 9.75; P<0.0001), FI (WMD 2.73; P<0.0001), and VFI (WMD 1.29; P<0.0001) were significantly higher whereas PI (WMD -1.08; P=0.001) and RI (WMD -0.26; P<0.0001) were significantly lower in women with polycystic ovarian syndrome (PCOS) than in normal women. In women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), antral follicle count was positively correlated with VI (r=0.24; P=0.001), FI (r=0.42; P<0.0001), and VFI (r=0.25; P=0.002). In women with PCOS, testosterone had statistically non-significant correlations with VI (r=0.40; P=0.081), and VFI (r=0.39; P=0.063) and was inversely correlated with PI (r=-0.30; P<0.0001) and RI (r=-0.48; P<0.0001). In women with PCOS, luteinizing hormone (LH) was inversely correlated with PI (r=-0.26; P=0.086) and RI (r=-0.25; P=0.007). Conclusions: Doppler indices are found significantly different in women with and without ovarian dysfunction and have significant correlations with markers of ovarian dysfunction. These results support the use of Doppler ultrasound to examine ovarian dysfunction. High statistical heterogeneity observed herein should be studies in future investigations.

Fine control for the preparation of ceria nanorods (111).

The morphologies and exposed surfaces of ceria nanocrystals are important factors in determining their performance. In order to establish a structure-property relationship for ceria nanomaterials, it is essential to have materials with well-defined morphologies and specific exposed facets. This is also crucial for acquiring high resolution 17O solid-state NMR spectra. In this study, we explore the synthesis conditions for preparing CeO2 nanorods with exposed (111) facets. The effects of alkali concentration, hydrothermal temperature and time, cerium source and oxidation agent are investigated and optimal synthesis conditions are found. The resulting CeO2 nanorods show very narrow 17O NMR peaks for the oxygen ions in the first, second and third layers, providing a foundation for future research on mechanisms involving ceria materials using 17O solid-state NMR spectroscopy.

Altered brain networks and connections in chronic heart failure patients complicated with cognitive impairment.

Objective: Accumulating evidence shows that cognitive impairment (CI) in chronic heart failure (CHF) patients is related to brain network dysfunction. This study investigated brain network structure and rich-club organization in chronic heart failure patients with cognitive impairment based on graph analysis of diffusion tensor imaging data. Methods: The brain structure networks of 30 CHF patients without CI and 30 CHF patients with CI were constructed. Using graph theory analysis and rich-club analysis, changes in global and local characteristics of the subjects' brain network and rich-club organization were quantitatively calculated, and the correlation with cognitive function was analyzed. Results: Compared to the CHF patients in the group without CI group, the CHF patients in the group with CI group had lower global efficiency, local efficiency, clustering coefficient, the small-world attribute, and increased shortest path length. The CHF patients with CI group showed lower nodal degree centrality in the fusiform gyrus on the right (FFG.R) and nodal efficiency in the orbital superior frontal gyrus on the left (ORB sup. L), the orbital inferior frontal gyrus on the left (ORB inf. L), and the posterior cingulate gyrus on the right (PCG.R) compared with CHF patients without CI group. The CHF patients with CI group showed a smaller fiber number of edges in specific regions. In CHF patients with CI, global efficiency, local efficiency and the connected edge of the orbital superior frontal gyrus on the right (ORB sup. R) to the orbital middle frontal gyrus on the right (ORB mid. R) were positively correlated with Visuospatial/Executive function. The connected edge of the orbital superior frontal gyrus on the right to the orbital inferior frontal gyrus on the right (ORB inf. R) is positively correlated to attention/calculation. Compared with the CHF patients without CI group, the connection strength of feeder connection and local connection in CHF patients with CI group was significantly reduced, although the strength of rich-club connection in CHF patients complicated with CI group was decreased compared with the control, there was no statistical difference. In addition, the rich-club connection strength was related to the orientation (direction force) of the Montreal cognitive assessment (MoCA) scale, and the feeder and local connection strength was related to Visuospatial/Executive function of MoCA scale in the CHF patients with CI. Conclusion: Chronic heart failure patients with CI exhibited lower global and local brain network properties, reduced white matter fiber connectivity, as well as a decreased strength in local and feeder connections in key brain regions. The disrupted brain network characteristics and connectivity was associated with cognitive impairment in CHF patients. Our findings suggest that impaired brain network properties and decreased connectivity, a feature of progressive disruption of brain networks, predict the development of cognitive impairment in patients with chronic heart failure.

Brain diffusion tensor imaging reveals altered connections and networks in epilepsy patients.

Introduction: Accumulating evidence shows that epilepsy is a disease caused by brain network dysfunction. This study explored changes in brain network structure in epilepsy patients based on graph analysis of diffusion tensor imaging data. Methods: The brain structure networks of 42 healthy control individuals and 26 epilepsy patients were constructed. Using graph theory analysis, global and local network topology parameters of the brain structure network were calculated, and changes in global and local characteristics of the brain network in epilepsy patients were quantitatively analyzed. Results: Compared with the healthy control group, the epilepsy patient group showed lower global efficiency, local efficiency, clustering coefficient, and a longer shortest path length. Both healthy control individuals and epilepsy patients showed small-world attributes, with no significant difference between groups. The epilepsy patient group showed lower nodal local efficiency and nodal clustering coefficient in the right olfactory cortex and right rectus and lower nodal degree centrality in the right olfactory cortex and the left paracentral lobular compared with the healthy control group. In addition, the epilepsy patient group showed a smaller fiber number of edges in specific regions of the frontal lobe, temporal lobe, and default mode network, indicating reduced connection strength. Discussion: Epilepsy patients exhibited lower global and local brain network properties as well as reduced white matter fiber connectivity in key brain regions. These findings further support the idea that epilepsy is a brain network disorder.

[Characteristics of histone deacetylase 9 in peripheral blood of patients with bronchial asthma].

OBJECTIVE: To investigate the expression pattern of histone deacetylase 9 (HDAC9) in peripheral blood of asthmatics and its effect on immune cells (Th2, Th17, Tregs) involved in the pathogenesis of asthma. METHODS: Forty-seven asthmatics from Ruijin Hospital were recruited and assigned to intermittent, mild and moderate-severe groups. Lung function test and Asthma Control Questionnaire were performed to evaluate asthma control and severity. Twenty healthy donors were enrolled as controls. GATA3, IL-4, and HDAC9 mRNA expression levels were measured by SYRB Green Real-time PCR. The cytokine IL-17-mainly produced by Th17 cells and TGF-ß-mainly produced by Treg cells, were measured by ELISA. RESULTS: The GATA3 and IL-4 mRNA expression levels (28.12 ± 7.57 and 743.6 ± 312.8) were up-regulated in asthmatics as compared to the healthy controls [0.56 ± 0.22, 0.7 ± 0.8 (U = 16.00, 37.00, P < 0.01)]. The HDAC9 mRNA expression levels of intermittent, mild and moderate-severe groups were 3.20 ± 0.50, 89.6 ± 18.0, 323.0 ± 65.3, respectively, which were associated with the severity of disease (H = 11.32, P < 0.05). The level of IL-17 in asthmatic group was (83 ± 55) ng/L, which was up-regulated as compared to the healthy control [(34 ± 22) ng/L (U = 153.50, P < 0.01)]. The level of TGF-ß was decreased in the asthmatic groups as compared to the healthy control, but the difference did not reach significance. HDAC9 mRNA expression level was positively correlated with GATA3 mRNA expression level (r = 0.482, P < 0.05), and also with IL-4 mRNA expression (r = 0.432, P < 0.05) and IL-17 (r = 0.538, P < 0.05), but negatively correlated with TGF-ß (r = -0.417, P < 0.05). In patients with moderate-severe asthma, HDAC9 mRNA expression level was negatively correlated with FEV(1)% (r = -0.657, P < 0.05). CONCLUSION: HDAC9 mRNA expression was up-regulated in peripheral blood of asthmatics, which was not only associate with the Th2 master transcriptional factors GATA3, cytokine IL-4 mRNA, Th17 and Treg cell-related cytokines, but also with FEV(1)% in moderate-severe asthma.

Effectiveness and Safety of DOACs in Atrial Fibrillation Patients Undergoing Catheter Ablation: Results from the China Atrial Fibrillation (China-AF) Registry.

BACKGROUND: Direct oral anticoagulants (DOACs) have increasingly become an alternative to warfarin in atrial fibrillation (AF) patients. Nonetheless, data on the effectiveness and safety of DOACs in periprocedural of catheter ablation (CA) in real-world practice was relatively rare. METHODS AND RESULTS: 3385 AF patients underwent initial CA and never used oral anticoagulant before enrollment between April 2013 and December 2018 were involved from China Atrial Fibrillation (China-AF) Registry. Warfarin, rivaroxaban and dabigatran were used in 1896 (56.0%), 718 (21.2%), and 771 (22.8%) patients, respectively. Propensity score matching was used to balance covariates across study groups. No significant differences were observed in rivaroxaban-warfarin, dabigatran-warfarin and dabigatran-rivaroxaban cohort for thromboembolic (TE) and major bleeding (MB) incidence. Similar results were also revealed in low-dose rivaroxaban (RLD)-warfarin, low-dose dabigatran (DLD)-warfarin and DLD-RLD cohort. However, the risk of non-MB was higher not only on standard-dose of rivaroxaban but also on RLD when compared with warfarin and with DLD, respectively. CONCLUSIONS: In this study, the incidence of TE and MB were both comparable in standard- or low-dose DOACs versus warfarin and between the two DOACs, whereas the risk of non-MB was higher in rivaroxaban than in warfarin and in RLD than in DLD.