Search

Introduction: Despite the available secondary preventive treatments, the management of stable coronary artery disease (SCAD) remains challenging. Intermediate coronary lesion (ICL), defined as luminal stenosis between 50% and 70%, is a key stage of SCAD. However, existing therapeutic strategies are limitated in delaying plaque progression and associated with various adverse effects and economic burdens. Qing-Xin-Jie-Yu Granules (QXJYG) with proven anti-platelet, anti-inflammatory, and lipid-lowering effects may compensate for the drawbacks of current treatments and can be tested as a complementary therapy. Therefore, this study aims to investigate the efficacy and safety of QXJYG in treating ICL, with a particular focus on its impact on myocardial ischemia and plaque progression. Materials and methods: This is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 120 participants with ICL will be randomly assigned to two groups in a 1:1 ratio. In addition to basic medications, the intervention group will receive QXJYG, while the control group will receive a placebo for over 6 months, followed by a 12-month follow-up. The primary efficacy outcome is computed tomography-derived fractional flow reserve. The secondary outcomes include the degree of coronary stenosis, coronary artery calcification score, Gensini score, Seattle Angina Questionnaire score, high-sensitivity C-reactive protein, matrix metalloproteinase-9, blood lipids, and carotid artery ultrasound parameters. Major adverse cardiovascular events are recorded as endpoints. The safety outcomes include composite events of bleeding, laboratory test results, and adverse events. Clinical visits are scheduled at baseline, every 2 months during the treatment, and after a 12-month follow-up. Discussion: This trial is anticipated to yield reliable results to verify the efficacy and safety of QXJYG in the treatment of ICL, which will provide novel insights to help address the prevailing therapeutic dilemma of ICL, thereby facilitating for the management of SCAD. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200059262. Registered on April 27, 2022. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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‐β 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. Synopsis: The ubiquitin‐specific peptidase 44 (USP44) interacts with FOXP3 and stabilizes the transcription factor by removing K48‐linked ubiquitin modifications. USP44 is essential for the establishment of fully functional regulatory T cells. USP44 is a deubiquitinase for FOXP3 and is up‐regulated via TGF‐beta signaling.USP44 cooperates with USP7 to stabilize FOXP3.Tregs with USP44 deficiency are less effective suppressors than wild type controls. [ABSTRACT FROM AUTHOR]

The treatment methods of asphalt pavement diseases, and the preparation and testing methods of modified asphalt crack paste specimens are introduced. The impact of plasticiser, modifier, tackifier and padding on softening point, low temperature flexibility, peel strength, shear strength and continuous cohesiveness of asphalt/crack paste are discussed respectively, and the results showed that, the addition of plasticizer could improve the performance of asphalt/crack paste. Then a suitable material ratio was obtained in combination of environmental protection and the cost, and the performance of the crack paste prepared according to this ratio were tested. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

Viscosities and liquid structures of Ag100-xSix (x=5, 7, 9, 11, at.%) melts were studied by an oscillating viscometer and an X-ray diffractometer. Temperature dependence of viscosity and the correlation length D all can be fitted well by Arrhenius equation. The activation energy for viscous flow Ea,V and the activation energy for structural evolution Ea,D all increase with increasing Si content. Above the liquidus temperature, the coordination number Ns, the correlation radius rc, the atom numbers in the cluster Nc and the correlation length D all increase with decreasing temperature. Among them, rc and Nc show a significant increase near the liquidus temperature. In the liquid-solid interval, the structural parameters show different behaviors with temperature due to the influence of the liquid-solid equilibrium reaction of the precipitation phase. Based on the investigated viscosity and structure, the fragility parameter of superheated melts M and the structural fragility parameter Fs were calculated. Both M and Fs increase with increasing silicon content. This work provides us a further understanding of the liquid-solid transition from the perspective of liquid structure and dynamics. [ABSTRACT FROM AUTHOR]

Background: Treg cells play an important role in the pathogenic progress of asthma.Objective: To address the alterations of Treg cells in asthma.Methods: Proliferation-and function-associated markers of Treg cells along with the percentage of Treg cells producing some cytokine from asthmatics and healthy subjects were analyzed by flow cytometry. Besides, the expressions of USP21 and PIM2 in Treg cells were measured by cell immunochemistry after Treg cells were sorted.Results: Treg cells from asthmatic patients showed lower proliferation activity and were more likely to be apoptotic. These cells expressed lower levels of GITR, CTLA-4, Nrp-1, and IL-10 compared to those from the healthy control. Th2-like Treg cells increased in asthmatic patients, while the percentage of IFN-r+ Treg cells was similar between two groups. Moreover, the percentage of IL-4+ Treg cells is related to the asthma control. Treg cells from asthmatic patients expressed more FOXP3 as well as GATA3; the expression level of GATA3 negatively correlated with FEV1%pred. Increased expressions of USP21 and PIM2 in Treg cells from asthmatic patients were found.Conclusion: Treg cells decreased in asthmatic patients, with an impaired immunosupression function and a Th2-like phenotype, which may be due to overexpression of GATA3 and FOXP3, regulated by USP21 and PIM2, respectively. [ABSTRACT FROM AUTHOR]

The viscosity and liquid structure of Cu100-xSnx (x=10, 20, 30, 40, at.%) melts were investigated. Temperature dependence of viscosity η and correlation length D all shows an exponential decay function (Arrhenius-type equation), which is similar to our former studied Cu-Ag alloys. The correlation between viscosity and liquid structure had been studied. A simple relation between viscosity and correlation length D was found. The ratio of D and η shows a linear relationship with temperature, which is different from our former studied results in Cu-Ag alloys. Among the four Cu-Sn alloys, Cu80Sn20 and Cu70Sn30 alloys have higher activation energy for viscous flow (Ea,V), activation energy for structural evolution (Ea,D), and the slope (γ) of the linear relationship of D/η with temperature due to the Cu3Sn clusters formation. [ABSTRACT FROM AUTHOR]

The pumped-storage power station is an efficient stability regulator of the power grid. However, due to the instability of the pump-turbine in the S-shaped characteristic region, rotational speed fluctuation is easy to occur in the speed no-load condition, making synchronization with and connection to the grid difficult. To investigate the key factors of these difficult grid connections, the start-up processes of a practical pump-turbine under the lowest head condition were simulated by using the three-dimensional CFD method, in which the governor regulating equations with different regulating parameters were integrated successfully. The results show that the working points oscillate with the fluctuations of rotational speed, discharge, and torque, and different regulating parameters have a significant influence on the dynamic histories. In addition, the internal flow patterns, especially the backflows at the runner inlet, keep apparent values at the middle span (0.5 span) but have regular transitions near the shroud side (0.7–0.8 span). The faster the guide vanes adjust, the faster the backflows change, and the larger the macro parameters fluctuate. Overall, the instability of the start-up is the result of the periodical evolutions of backflows at the runner inlet, because the trend and period of the radial velocities at different inlet span locations are consistent with those of the discharge. [ABSTRACT FROM AUTHOR]

The clearance flow around the pump-turbine runner has significant influences on unit vibrations, which may cause accidents in transient processes. The dynamic hydraulic forces and flow patterns in the clearance flow channel (CFC) of a low specific-speed pump-turbine were analyzed based on 3D CFD simulations during the runaway oscillating process. It is shown that the axial force of the runner periodically fluctuates with large amplitudes, and its components in CFC and the main flow channel (MFC) demonstrate a similar significance level. The CFC component was formulated as a function of the clearance inlet pressure and rotational speed, while the MFC component as a function of the momentum changing rate and the runner outlet pressure force. The fluctuation of runner radial force is mainly caused by the flow evolution in MFC, however, the flow in CFC aggravates it. The pressure in CFC shows a few pulsating signals from MFC, and the radial pressure drop in CFC is proportional to the square of both radius and rotational speed. In CFC, strong rotating shear flow containing a velocity core region in the circumferential direction is formed, and rotational speed is the dominant factor. [ABSTRACT FROM AUTHOR]

Abstract: We report a liquid–liquid phase transition (LLPT) in Cu60Sn40 alloy suggested by the results of both the X-ray scattering experiment and viscosity measurement and verified by differential scanning calorimetry (DSC). The results show that a reversible LLPT (L(Cu3Sn)+L(Sn)⇔L(Cu60Sn40)) may occur in the heating and cooling processes. The findings may throw light on the nature of liquids and enrich the knowledge of liquid state, further more be helpful to understand the melting and freezing mechanism. [Copyright &y& Elsevier]

Background. Traditional mass spectrometry detection methods have low detection efficiency for low-abundance proteins, thus limiting the application of proteomic analysis in the diagnosis of preeclampsia. Magnetic nanomaterials have good superparamagnetism and have obvious advantages in the field of biological separation and enrichment. Aim. The objective of this study is to explore the value of superparamagnetic iron oxide nanoparticles in the proteomic analysis of preeclampsia. Materials and Methods. 42 patients and 40 normal pregnant women were selected in this study for analysis. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to evaluate the function of these differential proteins. Proteomic analysis was used to analyze the differential proteins. Color Doppler ultrasound technology was used to detect changes in the blood flow of the fetal umbilical artery and cerebral artery. Results. 16 differential proteins in the serum of pregnant women with preeclampsia and normal pregnant women were detected. The 16 proteins are mainly related to angiogenesis and endothelial function proteins, coagulation cascade proteins, placental growth factor, and so on. Biological function analysis revealed that these proteins are mainly enriched in the nuclear factor kB (NF-κB) signaling pathway. Moreover, our data suggested that compared with the fetus in the uterus of normal pregnant women, the umbilical artery S/D, PI, and RI of the fetus in preeclampsia were greatly increased, and the cerebral artery S/D, PI, and RI were greatly decreased. Conclusion. Biological function analysis revealed that 16 proteins are mainly enriched in the NF-κB signaling pathway. Compared with the normal group, the umbilical artery S/D, PI, and RI of the preeclampsia group were greatly increased, and the cerebral artery S/D, PI, and RI were all greatly reduced. Our findings provided a more comprehensive reference for us to study the mechanism of preeclampsia at the molecular level and also provide data support for the screening of relevant markers for early diagnosis of preeclampsia. [ABSTRACT FROM AUTHOR]

Abstract: The liquid structures in the solidification process of the Cu100− x Sn x (x =10, 20, 30, 40) alloys were investigated by X-ray diffraction method. The results show that the Cu3Sn and quasi Cu3Sn structures exist in the Cu–Sn liquids. Which arouses an obvious structure change indicated by the correlation radius r c at about 900°C. In addition, the structure change induced by the liquid–solid transition at about 30–40°C below the liquidus is also observed. [Copyright &y& Elsevier]

Abstract: A new concept, the structural fragility of liquids, has been proposed based on different structural changing behaviors with temperature. A fragility parameter, , was introduced to quantify the structural fragility, and the glass-forming ability (GFA) of some binary alloys was discussed subsequently. The results show that the structural fragility is closely related to the GFA of liquids, a smaller corresponds to a higher GFA. [Copyright &y& Elsevier]

Abstract: The atomic structures of liquid Cu–Ag alloys (Cu80Ag20, Cu60Ag40, Cu40Ag60 and Cu20Ag80) have been investigated in the solidification process by means of X-ray diffraction. The results show that the liquid structures of Cu–Ag alloys, which are micro-homogeneous and similar with their solid state, display quite stable changes on a large-scale range indicated by the correlation radius r c, although the short-range order structures change obviously around their liquidus (liquid–solid transformation). This is different from the results of the In30Sn70 alloy we previously reported, which shows an abrupt structure changes around its liquidus. In addition, the Gaussian peaks decomposition of the radial distribution functions (RDF(r)) was also performed to shed light on the element distribution and structure evolution in the whole solidification process especially around the liquidus. [Copyright &y& Elsevier]

Abstract: The atomic structure in the solidification process (from 1200 to 780 °C, and is about 950 and 780 °C respectively) of Cu80Ag20 binary alloy has been investigated by X-ray diffraction technique. The correlation radius and the atom numbers of the cluster show a little increasing with the temperature decreasing bellow 1100 °C. The correlation length D shows almost a linear change with the temperature. All these results indicate a quite stable structure change in the solidification process of Cu80Ag20 alloy. This is quite different from our former study on In30Sn70 alloy, which shows an abrupt increasing both for , and D around its liquidus. As liquid clusters play a crucial role in the forming of crystalline nucleus and they may serve as the embryo of the nucleus, which means two different nucleus forming mechanism. We consider the Cu80Ag20 like as stabilization mode and the In30Sn70 like as saltation mode. In addition, the moving of atoms in the solidification process is also discussed by the Gaussian peaks decomposing of the . [Copyright &y& Elsevier]

Abstract: X-ray diffraction experiment has been carried out on In30Sn70 binary alloy from normal liquid 400 °C to the temperature near the solidus 125 °C ( and is about 172 and 120 °C, respectively). The results show that the correlation radius , the correlation length D and the atom numbers have an abrupt increase near the liquidus with the temperature decreasing. Which indicates an abrupt structure change in the nucleus forming process. This result is different from our recent study on Cu80Ag20 alloy, which show a stable structure change around the liquidus. In addition, the coordination number comparing with the viscosity measurement indicates a temperature and component induced discontinuous structural change region between about 165 and 145 °C. [Copyright &y& Elsevier]

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Cheng, Hou, Li, Wang, Ma, Cheng, Ding and Feng.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MZ declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2023 Wang, Xu, Hou, Shi, Zhao, Gui, Wu, Dong, Xu, Shen, Cheng and Feng.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Cheng, Shi, Xu, Hou, Zhao, Gui, Wu, Dong, Xu, Shen, Cheng, Xue, Feng and Ding.)

Objective: To investigate the changes of brain network in epilepsy patients without intracranial lesions under resting conditions., Methods: Twenty-six non-lesional epileptic patients and 42 normal controls were enrolled for BOLD-fMRI examination. The differences in brain network topological characteristics and functional network connectivity between the epilepsy group and the healthy controls were compared using graph theory analysis and independent component analysis., Results: The area under the curve for local efficiency was significantly lower in the epilepsy patients compared with healthy controls, while there were no differences in global indicators. Patients with epilepsy had higher functional connectivity in 4 connected components than healthy controls (orbital superior frontal gyrus and medial superior frontal gyrus, medial superior frontal gyrus and angular gyrus, superior parietal gyrus and paracentral lobule, lingual gyrus, and thalamus). In addition, functional connectivity was enhanced in the default mode network, frontoparietal network, dorsal attention network, sensorimotor network, and auditory network in the epilepsy group., Conclusion: The topological characteristics and functional connectivity of brain networks are changed in in non-lesional epilepsy patients. Abnormal functional connectivity may suggest reduced brain efficiency in epilepsy patients and also may be a compensatory response to brain function early at earlier stages of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Hou, Lu, Zhao, Wang, Xu, Shi, Gui, Wu, Shen, Zhu, Xu, Dong, Cheng, Zhang and Feng.)

Objective: Rapid, accurate identification of patients with acute myocardial infarction (AMI) at high risk of in-hospital major adverse cardiac events (MACE) is critical for risk stratification and prompt management. This study aimed to develop a simple, accessible tool for predicting in-hospital MACE in Chinese patients with AMI., Design: Retrospective review of deidentified medical records., Setting: 38 urban and rural hospitals across diverse economic and geographic areas in China (Beijing, Henan Province and Jilin Province)., Participants: 15 009 patients discharged from hospital with a diagnosis of AMI., Main Outcome Measure: The primary outcome was MACE occurrence during index hospitalisation. A multivariate logistic regression model (China AMI Risk Model, CHARM) derived using patient data from Beijing (n=7329) and validated with data from Henan (n=4247) and Jilin (n=3433) was constructed to predict the primary outcome using variables of age, white cell count (WCC) and Killip class. C-statistics evaluated discrimination in the derivation and validation cohorts, with goodness-of-fit assessed using Hosmer-Lemeshow statistics., Results: The CHARM model included age (OR: 1.06 per 1-year increment, 95% CI 1.05 to 1.07, p<0.001), WCC (OR per 10 9 /L increment: 1.10 (95% CI 1.07 to 1.13), p<0.001) and Killip class (class II vs class I: OR 1.34 (95% CI 0.99 to 1.83), p=0.06; class III vs class I: OR 2.74 (95% CI 1.86 to 3.97), p<0.001; class IV vs class I: OR 14.12 (95% CI 10.35 to 19.29), p<0.001). C-statistics were similar between the derivation and validation datasets. CHARM had a higher true positive rate than the Thrombolysis In Myocardial Infarction score and similar to the Global Registry of Acute Coronary Events (GRACE). Hosmer-Lemeshow statistics were 5.5 (p=0.703) for derivation, 41.1 (p<0.001) for Henan, and 103.2 for Jilin (p<0.001) validation sets with CHARM, compared with 119.6, 34.0 and 459.1 with GRACE (all p<0.001)., Conclusions: The CHARM model provides an inexpensive, accurate and readily accessible tool for predicting in-hospital MACE in Chinese patients with AMI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: Asthma is a chronic inflammatory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). IL-33 is considered as one of the most critical molecules in asthma pathogenesis. IL-33 is stored in nucleus and passively released during necrosis. But little is known about whether living cells can release IL-33 and how this process is regulated., Objective: We sought to investigate the role of polymerase I and transcript release factor (PTRF) in IL-33 release and asthma pathogenesis., Methods: Ovalbumin (OVA)-induced asthma model in PTRF +/- mice were employed to dissect the role of PTRF in vivo . Then, further in vitro experiments were carried out to unwind the potential mechanism involved., Results: In OVA asthma model with challenge phase, PTRF +/- mice showed a greater airway hyper-reaction, with an intense airway inflammation and more eosinophils in bronchoalveolar lavage fluid (BALF). Consistently, more acute type 2 immune response in lung and a higher IL-33 level in BALF were found in PTRF +/- mice. In OVA asthma model without challenge phase, airway inflammation and local type 2 immune responses were comparable between control mice and PTRF +/- mice. Knockdown of PTRF in 16HBE led to a significantly increased level of IL-33 in cell culture supernatants in response to LPS or HDM. Immunoprecipitation assay clarified Y158 as the major phosphorylation site of PTRF, which was also critical for the interaction of IL-33 and PTRF. Overexpression of dephosphorylated mutant Y158F of PTRF sequestered IL-33 in nucleus together with PTRF and limited IL-33 extracellular secretion., Conclusion: Partial loss of PTRF led to a greater AHR and potent type 2 immune responses during challenge phase of asthma model, without influencing the sensitization phase. PTRF phosphorylation status determined subcellular location of PTRF and, therefore, regulated IL-33 release.

T cell‑associated inflammation, particularly type 2 inflammation, has an important role in asthma pathogenesis, which is suppressed by regulatory T cells (Tregs). Proviral integration site for Moloney murine leukemia virus 2 (PIM2), a member off the serine/threonine kinase family, promotes the growth and survival of T cells and influences the function of Treg cells. However, whether PIM2 affects asthma pathogenesis remains unclear. Peripheral blood mononuclear cells and Treg cells from asthmatic and healthy subjects were obtained, and the expression level of PIM2 was measured by reverse transcription‑quantitative polymerase chain reaction and immunocytochemistry. In addition, BALB/c female mice sensitized and challenged by ovalbumin were used as an asthma model, and PIM2 inhibitor was injected during the challenge period to observe the effect of PIM2 on asthma. The asthma symptoms were recorded, and airway hyper‑responsiveness (AHR), expression levels of cytokines in the serum or bronchoalveolar lavage fluid (BALF), and the number of BALF leukocytes were evaluated. In addition, hematoxylin and eosin staining and immunohistochemistry of lung tissues was performed. The results demonstrated that PIM2 was overexpressed in patients with asthma in natural Treg cells. Inhibition of PIM2 attenuated asthma symptoms, and improved AHR and airway inflammation compared with asthmatic mice without inhibition of PIM2. In addition, expression levels of interleukin (IL)‑10 and forkhead box protein 3 (FOXP3) in BALF were increased following PIM2 inhibition (IL‑10, 470.3±21.78 vs. 533.7±25.55 pg/ml, P<0.05; FOXP3, 259±4.68 vs. 279.3±3.68 pg/ml; asthma and PIM2 inhibition groups, respectively; P<0.05). In conclusion, PIM2 may exhibit an important role in asthma pathogenesis and exacerbate AHR, airway inflammation and asthma symptoms. These effects of PIM2 may be dependent on Treg cells and the secretion of IL‑10 by Tregs. The results of the present study suggest that PIM2 may be a potential target molecule for asthma treatment.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) results from NOTCH3 gene mutations, which lead to the degeneration of vascular smooth muscle cells (VSMCs). The clinical presentation of CADASIL patients is dependent on the impact of other vascular risk factors and the type of NOTCH3 mutation present., Methods: Here, we report a rare pathogenic mutation on exon 14 of the NOTCH3 gene in a Chinese family affected by CADASIL with phenotypic peculiarities. We performed genetic testing, clinical and neuropsychological examination, brain magnetic resonance images (MRI), and electron microscopy (EM) in skin biopsies., Results: NOTCH3 gene analysis revealed a c.2182CT substitution on exon 14, which is the first example of this mutation in a Chinese individual from the Han ancestry. Granular osmiophilic material (GOM) was found in the proband, and all patients had migraine, subcortical ischemic events, and mood disturbances, without progressive cognitive impairment. Cranial MRI further showed white matter hyperintensity, involving bilateral basal ganglia and multiple microbleeds (MBs), in the thalamus and brain stem., Conclusions: This study suggests that different missense mutations in NOTCH3 might contribute to atypical clinical features of CADASIL. This report also indicates that for individuals with a positive family history having clinical and neuroradiological findings suggestive of CADASIL, genetic testing and GOM detection should be performed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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.

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.