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Abstract Breast cancer (BC) is the most common malignancy with a poor prognosis. Radiotherapy is one of the leading traditional treatments for BC. However, radiotherapy-associated secondary diseases are severe issues for the treatment of BC. The present study integrated multi-omics data to investigate the molecular and epigenetic mechanisms involved in post-radiation BC. The differences in the expression of radiation-associated genes between post-radiation and pre-radiation BC samples were determined. Enrichment analysis revealed that these radiation-associated genes involved diverse biological functions and pathways in BC. Combining epigenetic data, we identified radiation-associated genes whose transcriptional changes might be associated with aberrant methylation. Then, we identified potential therapeutic targets and chemical drugs for post-radiation BC patient treatment by constructing a drug-target association network. Specifically, four radiation-associated genes (CD248, CCDC80, GADD45B, and MMP2) whose increased expression might be regulated by hypomethylation of the corresponding enhancer region were found to have excellent diagnostic effects and clinical prognostic value. Finally, we further used independent samples to verify CD248 expression and established a simple epigenetic regulatory model. In summary, this study provides novel insights for understanding the regulation of target genes mediated by DNA methylation and developing potential biomarkers for radiation-associated secondary diseases in BC.

Abstract Objective The relationship between body mass index (BMI) and sepsis prognosis remains highly controversial and uncertain. This study investigated the association between BMI and prognosis in patients with sepsis. Methods This retrospective observational cohort study included adult patients admitted to the intensive care unit (ICU) with sepsis from Medical Information Mart for Intensive Care-IV version 2.2 (MIMIC-IV V2.2) and eICU Collaborative Research Database (eICU-CRD). The cut-off value of BMI was identified by the restricted cubic spline (RCS) curve and included patients were categorized into two groups: the low BMI group (

Abstract Aim Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications and prognostic significance of CHIP and T2DM in patients diagnosed with ST-segment elevation myocardial infarction (STEMI). Methods Deep-targeted sequencing employing a unique molecular identifier (UMI) for the analysis of 42 CHIP mutations—achieving an impressive mean depth of coverage at 1000 × —was conducted on a cohort of 1430 patients diagnosed with acute myocardial infarction (473 patients with T2DM and 930 non-DM subjects). Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and T2DM was evaluated by the comparison of (i) the prevalence of CHIP mutations among individuals with diabetes versus those without, (ii) the clinical characteristics delineated by CHIP mutations within the cohort of diabetic patients and (iii) the prognostic significance and correlation of CHIP mutations with mortality rates in T2DM subjects. Furthermore, a two-sample bidirectional Mendelian randomization study was performed using genetic instruments from the genome-wide association study for TET2 mutation CH from the UK Biobank (UKB) (2041 cases,173,918 controls) to investigate the causal relationship with T2DM from the FinnGen consortium (65,085 cases and 335,112 controls), and vice versa. Results (i) Most commonly CHIP mutations exhibiting a variant allele fraction of ≥ 2.0% were identified in 50/473 (10.6%) patients with T2DM, demonstrating a greater prevalence compared to non-DM subjects [69/930 (7.4%); P

The outbreak and subsequent recurring waves of COVID −19 pose threats on the emergency management and people’s daily life, while the large-scale spatio-temporal epidemiological data have sure come in handy in epidemic surveillance. Nonetheless, some challenges remain to be addressed in terms of multi-source heterogeneous data fusion, deep mining, and comprehensive applications. The Spatio-Temporal Artificial Intelligence (STAI) technology, which focuses on integrating spatial related time-series data, artificial intelligence models, and digital tools to provide intelligent computing platforms and applications, opens up new opportunities for scientific epidemic control. To this end, we leverage STAI and long-term experience in location-based intelligent services in the work. Specifically, we devise and develop a STAI-driven digital infrastructure, namely, WAYZ Disease Control Intelligent Platform (WDCIP), which consists of a systematic framework for building pipelines from automatic spatio-temporal data collection, processing to AI-based analysis and inference implementation for providing appropriate applications serving various epidemic scenarios. According to the platform implementation logic, our work can be performed and summarized from three aspects: (1) a STAI-driven integrated system; (2) a hybrid GNN-based approach for hierarchical risk assessment (as the core algorithm of WDCIP); and (3) comprehensive applications for social epidemic containment. This work makes a pivotal contribution to facilitating the aggregation and full utilization of spatio-temporal epidemic data from multiple sources, where the real-time human mobility data generated by high-precision mobile positioning plays a vital role in sensing the spread of the epidemic. So far, WDCIP has accumulated more than 200 million users who have been served in life convenience and decision-making during the pandemic.

Abstract T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR β sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.

ObjectiveThis study aims to evaluate the effectiveness of Integrated Soil-Crop System Management (ISSM) and provide technical support for sustainable high yield and efficiency in regional agriculture.MethodsThe study compared the effects of no fertilization (Control), conventional farmer practices (FP), high-yield management (HY), and ISSM on maize yield and plant nutrient uptake. Measurements included grain yield, plant biomass, plant nutrient absorption, and soil nutrient content across different management strategies.ResultsOver the 12-year experimental period, a significant decline in grain yield was observed under the Control treatment, with a slight decrease in the FP treatment. In contrast, consistent yield increases were noted for the HY and ISSM treatments. The ISSM approach significantly enhanced the average yield and plant uptake of P and K by 26%, 24%, and 32%, respectively, approaching 98%, 91%, and 85% of the levels achieved in the HY treatment. Furthermore, the average use efficiency of P and K fertilizers in the ISSM treatment exceeded those in the FP treatment by 18.7% and 1.2%, respectively, and those in the HY treatment by 17.4% and 24.8%, respectively. The adoption of ISSM led to a significant increase in total and available P and K content within the 0–20 cm and 20–40 cm soil layers and enhanced the available P and K content across all aggregate size fractions within the 0–20 cm soil layer.ConclusionISSM is capable of achieving long-term high and stable yields for spring maize, enhancing the uptake and utilization of P and K in plants, and bolstering the soil’s capacity to supply these nutrients, thereby fostering the sustainable development of the entire soil-crop system.

Sestrin proteins, conserved family proteins which mainly induced by ROS, DNA damage, inflammation, and other injuries. Growing evidences proved sestrin proteins exert protective functions in cardiovascular diseases, chronic degenerative osteoarthritis, musculoskeletal diseases, aging and others, sestrin proteins exhibit an anti-inflammatory response, improving metabolism and other valuable character. However, there is no comprehensive and detailed summary and literature research on the intervention methods of sestrin proteins at present. As the advance of research during last several years, exercise training and other interventions are considered to be the potential methods to up-regulate expression level of protein. In view of the physiological function of this protein, a review of the main studies on regulating the expression level of this protein can provide a novel approach for the clinical treatment and scientific research. In present study, all related researches about interventions and potential mechanisms were reviewed and the mainstream methodologies were described.

Background: Randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy and safety of medical interventions. Phytotherapy, which plays a critical role in the prevention and treatment of many clinical conditions, is also evaluated by RCTs. In recent years, the transparency, methodology, and generalizability of RCTs, as well as disparities in gender and geographical location among researchers, have attracted much attention from the scientific community. However, these aspects of RCTs in phytotherapy interventions have not been fully evaluated. Therefore, a methodological project (i.e., SMART-PT, tranSparency and Methodological chAracteristics of Randomized controlled Trials of PhytoTherapy interventions) was designed to overcome these knowledge gaps and provide key references for relevant future RCTs. Methods: The SMART-PT project consists of five studies that will be conducted using RCTs derived from two high-impact phytotherapy journals, Phytomedicine and Phytotherapy Research. RCTs published in Phytomedicine and Phytotherapy Research were searched using the PubMed database from inception to February 13, 2023. Study selection was performed by two independent researchers, and data extraction and quality assessment will also be conducted independently by two researchers. First, we will investigate the reporting completeness, data-sharing level, and presence of spin among the included RCTs (Study 1). Second, we will evaluate the risk of bias in the included RCTs and the statistical fragility of primarily binary outcomes, and the likelihood ratio will be used to reinterpret statistically nonsignificant primary outcomes (Study 2). Third, we will evaluate the reporting completeness of phytotherapy interventions in the included RCTs as well as the trustworthiness of the RCTs (Study 3). Fourth, we will investigate the reporting of sociodemographic features and representation of participants in the included RCTs (Study 4). Finally, we will investigate the reporting completeness of the abstracts, the representation of gender, and geographical region of the listed authors among the included RCTs (Study 5). R 4.2.3, Stata 17/SE, and Excel 2019 will be used to analyze the data and create graphics. Results and Discussion: One-hundred and fifty-two double-arm, parallel-group, superiority RCTs were included in the SMART-PT project. The results of the five meta-research studies will be submitted for publication in peer-reviewed journals.

Abstract Background Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. Methods To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. Results The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. Conclusions The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.

Abstract Objects This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups. Methods Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan–Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted. Results During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a)

The long-term burial of organic carbon in marginal seas plays a critical role in Earth’s carbon cycle and climate change. However, the mechanism of organic carbon (OC) burial in the Okinawa Trough (OT) during glacial-interglacial timescales remains unclear. In this study, we analyzed the foraminiferal carbon isotopes, total organic carbon (TOC), and δ13C-TOC over the past 200 ka in core Z1 collected in the central OT. We aimed to reveal the history of OC burial in the middle Okinawa Trough during the past 200 ka, and we combined our findings with relevant paleoenvironmental indices to reveal underlying mechanisms. We found reduced surface primary productivity during MIS 6, which may indicate changes in the pathways of the Kuroshio Current (KC). Furthermore, we observed decoupling between high TOC flux and low OC burial during glacial periods. We proposed that the dilution effect caused by the high sedimentation rate and poor OC preservation during the glacial period resulted in the low TOC content. Ventilation of the North Pacific Intermediate Water (NPIW) regulated the redox conditions of the intermediate water in the Okinawa Trough. Additionally, the intensified Kuroshio Current during interglacial phases led to water column stratification, creating reducing conditions in the bottom water and facilitating improved OC preservation. Subsequently, the enhanced water column oxygenation resulting from the oxygen carried by the intensified glacial NPIW weakened the burial of OC. This study sheds new light on our understanding of the carbon cycle in marginal seas on a glacial-interglacial timescale.

Background and Objectives: Newborns as a vulnerable population are exposed to congenital and acquired infections during and after birth. There are several reports of the isolation and reporting of infectious agents (IAs) in early life of newborns with respiratory manifestations, and the present comprehensive study provides a snapshot of the current global situation of the prevalence of IAs in newborns with respiratory symptoms. Materials and Methods: A systematic search was conducted in main databases, including PubMed, Scopus, Web of science, and Google scholar. The pooled prevalence of infectious agents (IAs) in newborns was estimated using comprehensive meta-analysis software based on random effects model. Results: Out of 44 inclusive studies (50 datasets) for IAs in newborns, the pooled prevalence was estimated to be 12.2% (95% CI: 6.40-22.0%) and the highest and lowest prevalence of IAs was related to the Brazil (78.2%, 95% CI: 31.0-96.6%), and UK (0.01%, 95% CI 0.01-0.01%) respectively. Conclusion: The high prevalence of IAs in newborns emphasizes considers the necessary measures to prevent respiratory infections.

Objective: Vitamin D3 has the general properties of a lipid-soluble vitamin, but is also an active steroid hormone that can regulate the proliferation, apoptosis and differentiation of many tumor cells, and exerts anticancer activity against numerous malignancies. However, the mechanism underlying the effects of vitamin D3 on tumors is not fully understood. Here, we used network pharmacology and in vitro experimental approaches to explore the mechanism of vitamin D3 activity in the context of gastric cancer.Methods: The Targetnet, SuperPred, SwissTargetPrediction, and PharmMapper databases were screened for potential drug-related targets, while we used data from the PharmGKB, Drugbank, OMIM, DisGeNET, CTD, and GeneCards databases to identify potential targets associated with gastric cancer. Disease-drug crossover genes were obtained by constructing Venn diagrams. Gene ontology and Kyoto Encyclopedia of Genomes (KEGG) enrichment analyses of crossover genes were conducted and STRING was used to generate protein interaction networks and identify core targets. CCK-8 experiments were performed and apoptosis detected to assess the effect of vitamin D3 on gastric cancer cells. Western blotting was applied to detect p53/AMPK/mTOR signaling, as well as autophagy-, cell cycle-, and apoptosis-related proteins.Results: A total of 485 targets of vitamin D3 activity were obtained and 1200 gastric cancer disease-related targets discovered. Further, 60 potential targets for vitamin D3 in gastric cancer treatment were identified. KEGG analysis indicated that potential targets were mainly involved in the cell cycle, HIF-1 signaling, and the AMPK pathway, among other pathways. These findings were validated using cellular experiments, which demonstrated that the viability of AGS and SGC-7901 cells was impeded by vitamin D3. Further, vitamin D3 promoted apoptosis and inhibited the cell cycle in those cell lines, as well as activating the p53/AMPK/mTOR pathway, which promotes autophagy and inhibits tumor development.Conclusion: Our network pharmacological analyses provide preliminarily data supporting a role for vitamin D3 in promoting autophagy and apoptosis in gastric cancer cells, and in activating the p53/AMPK/mTOR pathway, which inhibits gastric cancer cell proliferation. Our findings demonstrate the molecular mechanism underlying the effect of vitamin D3 in cure of gastric cancer.

Abstract Aims This study aimed to investigate the association between trimethylamine N‐oxide (TMAO) and the prognosis and association between high‐sensitivity C‐reactive protein (hsCRP) and TMAO‐associated cardiovascular risk in patients with acute myocardial infarction (AMI) complicated by heart failure (HF). Methods and results A total of 985 patients presenting with AMI and HF were consecutively enrolled at the Fuwai Hospital between March 2017 and January 2020. Patients were stratified into groups according to tertiles of TMAO levels and the median hsCRP levels. The primary endpoint was major adverse cardiac events (MACE), including all‐cause death, recurrence of myocardial infarction, and rehospitalization due to HF. During a median follow‐up of 716 days, 138 (14.0%) patients experienced MACE. Cox regression analyses showed that the adjusted hazard ratio (HR) for MACE was higher in patients in tertile 3 [TMAO > 9.52 μmol/L, HR: 1.85, 95% confidence interval (CI): 1.18–2.89; P = 0.007] than in tertile 1 (TMAO

BackgroundWhereas the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s cognitive examination-revised (ACE-R) are commonly used tests for the detection of post-stroke cognitive impairment (PSCI), these instruments take 10–30 min to administer and do not assess processing speed, which is a critical impairment in PSCI. MemTrax (MTx) is a continuous recognition test, which evaluates complex information processing, accuracy, speed, and attention, in 2 min.AimTo evaluate whether MTx is an effective and practical tool for PSCI assessment.MethodsThis study enrolled acute ischemic stroke (AIS) patients who have assessed the cognitive status including MTx, clinical dementia rating (CDR), MoCA, Neuropsychiatric Inventory (NPI), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), the National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), and Barthel Index of activity of daily living (BI) combined with the physical examinations of the neurologic system at the 90-day (D90) after the AIS. The primary endpoint of this study was establishing MTx cut-offs for distinguishing PSCI from AIS.ResultsOf the 104 participants, 60 were classified to the PSCI group. The optimized cut-off value of MTx-%C (percent correct) was 78%, with a sensitivity and specificity for detecting PSCI from Non-PSCI of 90.0 and 84.1%, respectively, and an AUC of 0.919. Regarding the MTx-Cp (Composite score = MTx-%C/MTx-RT), using 46.3 as a cut-off value, the sensitivity and specificity for detecting PSCI from Non-PSCI were 80.0 and 93.2%, with an AUC of 0.925. Multivariate linear regression showed that PSCI reduced the MTx-%C (Coef. −14.18, 95% CI −18.41∼−9.95, p < 0.001) and prolonged the MTx-RT (response time) (Coef. 0.29, 95% CI 0.16∼0.43, p < 0.001) and reduced the MTx-CP (Coef. −19.11, 95% CI −24.29∼−13.93, p < 0.001).ConclusionMemTrax (MTx) is valid and effective for screening for PSCI among target patients and is a potentially valuable and practical tool in the clinical follow-up, monitoring, and case management of PSCI.

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers. Methods A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated. Results PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan–Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094–4.764, P = 0.028), but not in the whole cohort or non-diabetic patients. Conclusions The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.

Diarrhea is a severe bovine disease, globally prevalent in farm animals with a decrease in milk production and a low fertility rate. Cryptosporidium spp. are important zoonotic agents of bovine diarrhea. However, little is known about microbiota and short-chain fatty acids (SCFAs) changes in yaks infected with Cryptosporidium spp. Therefore, we performed 16S rRNA sequencing and detected the concentrations of SCFAs in Cryptosporidium-infected yaks. Results showed that over 80,000 raw and 70,000 filtered sequences were prevalent in yak samples. Shannon (p

Therapeutic focused ultrasound in combination with encapsulated microbubbles is being widely investigated for its ability to elicit bioeffects in the microvasculature, such as transient permeabilization for drug delivery or at higher pressures to achieve ‘antivascular’ effects. While it is well established that the behaviors of microbubbles are altered when they are situated within sufficiently small vessels, there is a paucity of data examining how the bubble population dynamics and emissions change as a function of channel (vessel) diameter over a size range relevant to therapeutic ultrasound, particularly at pressures relevant to antivascular ultrasound. Here we use acoustic emissions detection and high-speed microscopy (10 kframes/s) to examine the behavior of a polydisperse clinically employed agent (Definity®) in wall-less channels as their diameters are scaled from 1200 to 15 µm. Pressures are varied from 0.1 to 3 MPa using either a 5 ms pulse or a sequence of 0.1 ms pulses spaced at 1 ms, both of which have been previously employed in an in vivo context. With increasing pressure, the 1200 µm channel – on the order of small arteries and veins – exhibited inertial cavitation, 1/2 subharmonics and 3/2 ultraharmonics, consistent with numerous previous reports. The 200 and 100 µm channels – in the size range of larger microvessels less affected by therapeutic focused ultrasound - exhibited a distinctly different behavior, having muted development of 1/2 subharmonics and 3/2 ultraharmonics and reduced persistence. These were associated with radiation forces displacing bubbles to the distal wall and inducing clusters that then rapidly dissipated along with emissions. As the diameter transitioned to 50 and then 15 µm – a size regime that is most relevant to therapeutic focused ultrasound - there was a higher threshold for the onset of inertial cavitation as well as subharmonics and ultraharmonics, which importantly had more complex orders that are not normally reported. Clusters also occurred in these channels (e.g. at 3 MPa, the mean lateral and axial sizes were 23 and 72 µm in the 15 µm channel; 50 and 90 µm in the 50 µm channel), however in this case they occupied the entire lumens and displaced the wall boundaries. Damage to the 15 µm channel was observed for both pulse types, but at a lower pressure for the long pulse. Experiments conducted with a ‘nanobubble’ (

Abstract Aim The present study aimed to explore these characteristics, particularly thin-cap fibroatheroma (TCFA), in relation to residual syntax score (rSS) in patients who presented with acute MI. Methods and outcomes A total of 434 consecutive patients with MI aged ≥18 years who had STEMI underwent primary PCI. Notably, compared with other subgroups, the presence of TCFA in culprit lesions and a higher level of rSS, were significantly associated with MACE. When rSS was divided into three groups, high rSS levels were associated with a higher incidence of MACE, in the subgroups of without TCFA (P = 0.005), plaque erosion (P = 0.045), macrophage infiltration (P = 0.026), and calcification (P = 0.002). AUC of ROC curve was 0.794 and 0.816, whereas the AUC of the survival ROC was 0.798 and 0.846. Conclusion The results of this study could be used in clinical practice to support risk stratification. Trial registration This study was registered at ClinicalTrials.gov as NCT03593928 .

Summary Impaired wound closure is an increasingly crucial clinical challenge. Recently, wound healing has shifted towards innovative treatments that exploit nanotechnology, biomaterials, biologics and phototherapy. Here, we constructed an engineered MG1363‐pMG36e‐mCXCL12 strain with pMG36e plasmid encoding stromal cell‐derived factor 1α (named CXCL12) and evaluated the synergistic effects of light‐emitting diode (LED) yellow light and MG1363‐pMG36e‐mCXCL12 on scald wounds in mice. The results indicated that the combined treatment with LED yellow light with mCXCL12 delivering strain accelerated wound closure, tissue remodelling, re‐epithelialization and hair follicle regeneration and inhibited over‐inflammation oppositely in the central and surrounding wounds by macroscopic, histopathologic and immunohistochemistry parameters. Furthermore, combination therapy increased the epidermal growth factor and Ki67‐positive cells and upregulated beta‐catenin (β‐catenin), cellular‐myelocytomatosis (c‐Myc), wingless‐type MMTV integration site family member 1 (Wnt1), Jagged 1, neurogenic locus notch homolog protein 1 (Notch 1) and hairy and enhancer of split 1 (Hes 1) protein levels of the Wnt and Notch signalling pathways. It also facilitated collagen fibrogenesis and deposition and improved the activities of hydroxyproline, superoxide dismutase and glutathione peroxidase in scalded granulation tissue, in addition to reducing the inflammatory factors interleukin 1 beta (IL‐1β) and tumour necrosis factor alpha (TNF‐α). The combined treatment effectively reduced skin pathogens Ralstonia and Acinetobacter to further reduce the risk of infection. Overall, combination of LED yellow light and MG1363‐pMG36e‐mCXCL12 represents a potential strategy for the treatment of cutaneous wounds.

Abstract Chip-to-chip and world-to-chip fluidic interconnections are paramount to enable the passage of liquids between component chips and to/from microfluidic systems. Unfortunately, most interconnect designs add additional physical constraints to chips with each additional interconnect leading to over-constrained microfluidic systems. The competing constraints provided by multiple interconnects induce strain in the chips, creating indeterminate dead volumes and misalignment between chips that comprise the microfluidic system. A novel, gasketless superhydrophobic fluidic interconnect (GSFI) that uses capillary forces to form a liquid bridge suspended between concentric through-holes and acting as a fluid passage was investigated. The GSFI decouples the alignment between component chips from the interconnect function and the attachment of the meniscus of the liquid bridge to the edges of the holes produces negligible dead volume. This passive seal was created by patterning parallel superhydrophobic surfaces (water contact angle ≥ 150°) around concentric microfluidic ports separated by a gap. The relative position of the two polymer chips was determined by passive kinematic constraints, three spherical ball bearings seated in v-grooves. A leakage pressure model derived from the Young–Laplace equation was used to estimate the leakage pressure at failure for the liquid bridge. Injection-molded, Cyclic Olefin Copolymer (COC) chip assemblies with assembly gaps from 3 to 240 µm were used to experimentally validate the model. The maximum leakage pressure measured for the GSFI was 21.4 kPa (3.1 psig), which corresponded to a measured mean assembly gap of 3 µm, and decreased to 0.5 kPa (0.073 psig) at a mean assembly gap of 240 µm. The effect of radial misalignment on the efficacy of the gasketless seals was tested and no significant effect was observed. This may be a function of how the liquid bridges are formed during the priming of the chip, but additional research is required to test that hypothesis.

Abstract Background Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor with grim prognosis. Aberrant DNA methylation is an epigenetic mechanism that promotes GBM carcinogenesis, while the function of DNA methylation at enhancer regions in GBM remains poorly described. Results We integrated multi-omics data to identify differential methylation enhancer region (DMER)-genes and revealed global enhancer hypomethylation in GBM. In addition, a DMER-mediated target genes regulatory network and functional enrichment analysis of target genes that might be regulated by hypomethylation enhancer regions showed that aberrant enhancer regions could contribute to tumorigenesis and progression in GBM. Further, we identified 22 modules in which lncRNAs and mRNAs synergistically competed with each other. Finally, through the construction of drug-target association networks, our study identified potential small-molecule drugs for GBM treatment. Conclusions Our study provides novel insights for understanding the regulation of aberrant enhancer region methylation and developing methylation-based biomarkers for the diagnosis and treatment of GBM.

Diarrhea is a word-widely severe disease coupled with gastrointestinal dysfunction, especially in cattle causing huge economic losses. However, the effects of currently implemented measures are still not enough to prevent diarrhea. Previously we found that dropped short-chain fatty acids in diarrhea yaks, and butyrate is commonly known to be related to the epithelial barrier function and intestinal inflammation. However, it is still unknown whether sodium acetate/sodium butyrate could alleviate diarrhea in animals. The present study is carried out to explore the potential effects of sodium acetate/sodium butyrate on lipopolysaccharide-induced diarrhea in mice. Fifty ICR mice were randomly divided into control (C), LPS-induced (L), and sodium acetate/sodium butyrate (D, B, A)-treated groups. Serum and intestine samples were collected to examine inflammatory cytokines, antioxidant levels, relative gene expressions via real-time PCR assay, and gut microbiota changes through high-throughput sequencing. Results indicated that LPS decreased the villus height (p < 0.0001), increased the crypt depth (p < 0.05), and lowered the villus height to crypt depth ratio (p < 0.0001), while sodium acetate/sodium butyrate supplementation caused a significant increase in the villus height (p < 0.001), decrease in the crypt depth (p < 0.01), and increase in the villus height to crypt depth ratio (p < 0.001), especially. In mice treated with LPS, it was found that the serum level of IL-1β, TNF-α (p < 0.001), and MDA (p < 0.01) was significantly higher; however, sodium acetate/sodium butyrate supplementation significantly reduced IL-1β (p < 0.001), TNF-α (p < 0.01), and MDA (p < 0.01), respectively. A total of 19 genera were detected among mouse groups; LPS challenge decreased the abundance of Lactobacillus, unidentified F16, unidentified_S24-7, Adlercreutzia, Ruminococcus, unclassified Pseudomonadales, [Ruminococcus], Acetobacter, cc 1, Rhodococcus, unclassified Comamonadaceae, Faecalibacterium, and Cupriavidus, while increased Shigella, Rhodococcus, unclassified Comamonadaceae, and unclassified Pseudomonadales in group L. Interestingly, sodium acetate/sodium butyrate supplementation increased Lactobacillus, unidentified F16, Adlercreutzia, Ruminococcus, [Ruminococcus], unidentified F16, cc 115, Acetobacter, Faecalibacterium, and Cupriavidus, while decreased Shigella, unclassified Enterobacteriaceae, unclassified Pseudomonadales, Rhodococcus, and unclassified Comamonadaceae. LPS treatment upregulated the expressions of ZO-1 (p < 0.01) and NLRP3 (p < 0.0001) genes in mice; however, sodium acetate/sodium butyrate solution supplementation downregulated the expressions of ZO-1 (p < 0.05) and NLRP3 (p < 0.05) genes in treated mice. Also, the LPS challenge clearly downregulated the expression of Occludin (p < 0.001), Claudin (p < 0.0001), and Caspase-1 (p < 0.0001) genes, while sodium acetate/sodium butyrate solution supplementation upregulated those gene expressions in treated groups. The present study revealed that sodium acetate/sodium butyrate supplementation alleviated LPS-induced diarrhea in mice via enriching beneficial bacterium and decreasing pathogens, which could regulate oxidative damages and inflammatory responses via NLRP3/Caspase-1 signaling. The current results may give insights into the prevention and treatment of diarrhea.

Glioblastoma (GBM) is characterized by extensive genetic and phenotypic heterogeneity. However, it remains unexplored primarily how CpG island methylation abnormalities in promoter mediate glioblastoma typing. First, we presented a multi-omics scale map between glioblastoma sample clusters constructed based on promoter CpG island (PCGI) methylation-driven genes, using datasets including methylation profiles, expression profiles, and single-cell sequencing data from multiple highly annotated public clinical cohorts. Second, we identified differences in the tumor microenvironment between the two glioblastoma sample clusters and resolved key signaling pathways between cell clusters at the single-cell level based on comprehensive comparative analyses to investigate the reasons for survival differences between two of these clusters. Finally, we developed a diagnostic map and a prediction model for glioblastoma, and compared theoretical differences of drug sensitivity between two glioblastoma sample clusters. In summary, this study established a classification system for dissecting promoter CpG island methylation heterogeneity in glioblastoma and provides a new perspective for the diagnosis and treatment of glioblastoma.

Abstract Background and aim This prospective study explored plaque morphology according to the underlying culprit lesion pathology (rupture versus erosion) in relation to the triglyceride glucose (TyG) index in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention and optical coherence tomography (OCT) for culprit lesions to elucidate the effects of the TyG index and type of plaque on the incidence of major adverse cardiovascular events (MACEs). Methods and outcomes A total of 274 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. The TyG index was calculated using the formula ln[fasting TG (mg/dL) × fasting glucose (mg/dL)/2]. Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the TyG tertiles. MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke. In fully adjusted analyses, the middle tertile of TyG was significantly associated with greater rates of MACEs in patients with PR but not in those with PE (relative to the low tertile, HR [hazard ratio], 6.01; 95% confidence interval [CI], 1.25–28.88; P = 0.025). Cox regression models indicated a significantly higher HR for MACEs in patients in the middle tertile of TyG than in those in the low tertile of TyG after full additional adjustment (HR, 5.45; 95% CI, 1.10–27.09; P = 0.038). However, being in the high tertile of TyG independently and significantly increased the risk of major bleeding events among patients with PE (HR, 2.50; 95% CI, 1.11–5.65; P = 0.028). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the TyG index combined with the morphological characteristics of plaque after full adjustment was 0.881 (sensitivity = 94.74%, specificity = 78.04%, cut-off level = 0.73). Kaplan–Meier curves were generated for the cumulative incidence of MACEs for up to a median of 1.98 years stratified by tertiles of TyG among the PR and PE subgroups. Among patients with PR, there were significant differences among the tertiles of TyG (p = 0.030). Conclusion and relevance Microstructural OCT features of culprit lesions in combination with the TyG index, a surrogate estimate of insulin resistance, can be used in clinical practice to support risk stratification and predict adverse events in patients with STEMI.

Background: Small vessel disease (SVD) widely exists in patients with acute coronary syndrome. However, the plaque characteristic of SVD has not been investigated. Methods: Optical coherence tomography (OCT) of culprit lesion was examined in 576 patients with ST-segment elevation myocardial infarction (STEMI) and finally 404 patients with qualified images were analysed of plaque phenotypes and microstructure. The cohort was divided into three groups according to vessel diameters of culprit lesion which were measured by OCT. Major adverse cardiac events (MACEs) were recorded of each patient and compared among patients with different vessel diameters and plaque phenotypes. Results: Gender, age and body mass index (BMI) were significantly different among patients with different diameters of culprit vessels (98.4% vs. 85.7% vs.71.4%, p < 0.001; 40.0 ± 7.0 vs. 54.9 ± 6.6 vs. 68.9 ± 5.8, p < 0.001; 28.4 ± 4.0 vs. 25.8 ± 2.9 vs. 25.2 ± 3.0, p < 0.001, respectively). Moreover, patients with diameters of culprit lesion >3 mm presented with more incidence of plaque rupture and macrophage (57.7% vs. 42.1% vs. 46.2%, p = 0.015, 55.1% vs. 41.0% vs. 36.9%, p = 0.010). Total MACE did not differ among groups of different vessel diameters and plaque phenotypes. Conclusions: Vessel size of culprit lesion is significantly associated with plaque phenotype in patients with STEMI. However, patients with different diameters and plaque phenotypes showed no significant difference of clinical outcomes. Clinical Trial Registration: NCT03593928.

Summary: Background: The end plate plays an important role in intervertebral disc degeneration progression. The aim of the study was to examine the compositional and structural changes of the end plate with age and to investigate the correlation between end plate and disc degeneration by T1ρ and T2 map magnetic resonance imaging. Methods: There were 12 young monkeys (6-7 years old), 20 aged monkeys (14-17 years old) and 12 human participants (30-50 years old) in this study. T1ρ or T2 map values of the nucleus pulposus and end plate cartilage were analyzed according to Pfirrmann grades and age. Afterwards, micro computed tomography and histological analysis were used to confirm the end plate changes in monkeys. Pearson’s correlation was performed to investigate the relationship between end plate and disc degeneration. Results: In monkeys, T1ρ (r=-0.794, P

Archaeal ammonia oxidation is the most important intermediate pathway in regulating the oceanic nitrogen cycle; however, the study of its specific role on a geological time scale is restricted to a specific part of marginal seas; thus far, only in the southern South China Sea (SCS). To explore the spatial pattern of the role of archaeal ammonia oxidation in the SCS, the GDGT-[2]/[3] ratio (Glycerol Dialkyl Glycerol Tetraether), an indicator of the archaeal ammonia oxidation rate, was analyzed and examined from the collected data profiles since the last glacial period in the northern SCS. The results showed that the GDGT-[2]/[3] ratio in the northern SCS was opposite to that in the southern SCS, with higher GDGT-[2]/[3] values during the Holocene compared to the last glacial period. Based on existing published depths of thermocline (DOT) data in the northern SCS since 30 ka, we believe that hydrological structural variations induced by mesoscale eddies caused this difference. Therefore, physical processes are very important factors that control the nitrogen cycle over a long-time scale. This study may provide new insights into the understanding of the role of archaeal ammonia oxidation within the marine nitrogen cycle over geological time scale.

Background: Despite the recommendations from mainstream guidelines, the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) for acute coronary syndrome (ACS) patients without heart failure (HF) is controversial, as its evidence is lacking in the era of reperfusion and intensive secondary preventions. This study aimed to investigate the impacts of ACEI/ARB on outcomes of ACS patients without HF treated by percutaneous coronary intervention (PCI).Methods: A total of 2,397 non-HF ACS patients treated by PCI were retrospectively recruited. Prognostic impacts of ACEI/ARB were assessed by unadjusted analysis, followed by propensity score matching (PSM) and propensity score matching weight (PSMW) analysis to control the between-group differences. The primary outcome was a composite of all-cause death and recurrent myocardial infarction (MI).Results: Among the included patients, 1,805 (75.3%) were prescribed with ACEI/ARB at discharge. The median follow-up time was 727 (433–2016) days, with 129 (5.4%) primary endpoint events, consisting of 55 (2.3%) cases of all-cause death and 74 (3.1%) cases of recurrent MI. The use of ACEI/ARB was not associated with significant risk reduction of primary endpoint events in unadjusted analysis (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.64–1.39, p = 0.779), PSM analysis (HR: 0.94, 95% CI: 0.60–1.47, p = 0.784), and PSMW analysis (HR: 0.91, 95% CI: 0.55–1.49, p = 0.704). Similar results were observed for secondary outcomes of all-cause death, cardiac death, and recurrent MI.Conclusion: For ACS patients without HF, the use of ACEI/ARB was not associated with lower risk of death or recurrent MI after PCI.

In previous deep learning-based fault diagnosis methods for rotating machinery, the method of directly feeding one-dimensional data into convolutional neural networks can lead to the loss of important fault features. To address the problem, a novel rotating machinery fault diagnosis model based on a rainbow recursive plot (RRP) is proposed. Our main innovation and contributions are: First, a RRP is proposed to convert the one-dimensional vibration signal from the rotating machinery into a two-dimensional color image, facilitating the capturing of more significant fault information. Second, a new CNN based on LeNet-5 is devised, which extracts a feature that describes substantial fault information from the converted two-dimensional color image, thus performing fault diagnosis recognition accurately. The public rolling bearing datasets and the online fault diagnosis platform are adopted to verify proposed method performance. Experiments on public datasets show that the proposed method can improve the accurate rate of recognition to 97.86%. More importantly, online experiment on the self-made fault diagnosis platform demonstrates that our approach achieves the best comprehensive performance in terms of recognition speed and accuracy compared to mainstream algorithms.

The spatial-numerical associations of response codes (SNARC) effect reveals that individuals can represent numbers spatially. In this study, event-related potential (ERP) technology was used to probe the effect of verbal-spatial task instructions on spatial-numerical association coding by using digit parity and magnitude judgment tasks, with the numbers 1–9 (except 5) and Chinese word labels (“left” and “right”) as experimental materials. The behavioral results of Experiment 1 showed that the SNARC effect was mainly based on verbal-spatial coding and appeared when the stimulus onset asynchrony (SOA) between the presentation of the verbal labels and the target digit was 0 ms. ERP results did not reveal any significant SNARC-related effects in either the N1 or P3 components. The behavioral results of Experiment 2 again showed that the SNARC effect was dominated by verbal-spatial coding. ERP results showed that significant effects related to verbal-spatial coding were found in both the early positive deflection of the stimulus-locked lateralized readiness potential (S-LRP) and the latency of the response-locked LRP (R-LRP). Hence, in this study, the nature of the spatial coding of the digit magnitudes was influenced by the processing of the word labels and affected both the response selection and response preparation stages.

Background and AimThis study aimed to develop and validate separate risk prediction models for thrombosis events (TEs) and major bleeding (MB) in patients with multivessel coronary artery lesions who had undergone primary percutaneous coronary intervention (PCI).Methods and ResultsThrombosis events (TEs) were defined as the composite of myocardial infarction recurrence or ischemic cerebrovascular events, whereas MB was defined as the occurrence of bleeding academic research consortium (BARC) three or five bleeding. The derivation and validation cohorts comprised 2,976 patients who underwent primary PCI between January 2010 and June 2017. At a median follow-up of 3.07 years (1,122 days), TEs and MB occurred in 167 and 98 patients, respectively. Independent predictors of TEs were older age, prior PCI, non-ST elevated MI (NSTEMI), and stent thrombosis (ST). Independent predictors of MB were triple therapy at discharge, coronary artery bifurcation lesions, lesion restenosis, target lesion of the left main coronary artery, stent thrombosis, non-use of IABP during primary PCI, type A/B according to the American College of Cardiology classification of the coronary lesion, and PTCA. In the derivation and validation cohorts, the areas under the curve were 0.817 and 0.82 for thrombosis and 0.886 and 0.976 for bleeding, respectively. In the derivation cohort, high thrombotic risk (n = 755) was associated with higher 3-year incidence of TEs, major adverse cardiovascular events (MACEs), and all-cause death compared to low risk (n = 1,275) (p = 0.0022, 0.019, and 0.012, respectively). High bleeding risk (n = 1,675) was associated with higher incidence of bleeding, MACEs, and cardiac death compared to low risk (n = 355) (p < 0.0001).ConclusionSimple risk scores can be useful in predicting risks of ischemic and bleeding events after primary PCI, thereby stratifying thrombotic or MB risks and facilitating clinical decisions.

BackgroundPrevious studies reported the cardiac protection effect of preinfarction angina (PIA) in patients with acute myocardial infarction (AMI). We sought to identify culprit-plaque morphology and clinical outcomes associated with PIA in patients with ST-segment elevation myocardial infarction (STEMI) using optical coherence tomography (OCT).Methods and ResultsA total of 279 patients with STEMI between March 2017 and March 2019 who underwent intravascular OCT of the culprit lesion were prospectively included. Of them, 153 (54.8%) patients were presented with PIA. No differences were observed in clinical and angiographic data between the two groups, except STEMI onset with exertion was significantly less common in the PIA group (24.2 vs. 40.5%, p = 0.004). Patients with PIA exhibited a significantly lower incidence of plaque rupture (40.5 vs. 61.9%, p < 0.001) and lipid-rich plaques (48.4 vs. 69.0%, p = 0.001). The thin-cap fibroatheroma (TCFA) prevalence was lower in the PIA group, presenting a thicker fibrous cap thickness, although statistically significant differences were not observed (20.3 vs. 30.2%, p = 0.070; 129.1 ± 92.0 vs. 111.4 ± 78.1 μm, p = 0.088; respectively). The multivariate logistic regression analysis indicated that PIA was an independent negative predictor of plaque rupture (odds ratio: 0.44, 95% CI: 0.268–0.725, p = 0.001). No significant differences in clinical outcomes were observed besides unplanned revascularization.ConclusionCompared with the non-PIA group, STEMI patients with PIA showed a significantly lower prevalence of plaque rupture and lipid-rich plaques in culprit lesion, implying different mechanisms of STEMI attack in these two groups.

ObjectiveTo evaluate and compare the predictive value of Face, Arm, Speech Test (FAST) and Balance, Eyes, Face, Arm, Speech, Time (BEFAST) scale in the acute ischemic stroke (AIS).MethodsWe searched Medline and Ovid databases for relevant literature in the English language. There were no limitations on the date. The sensitivity, specificity, likelihood ratio, and diagnostic odds ratio were pooled for meta-analysis. The symmetric receiver operator characteristic curve and Fagan's Nomogram were drawn, and meta-regression and subgroup analysis were used to explore the source of heterogeneity.ResultsA total of 9 studies, including 6,151 participants, were analyzed. The combined sensitivity of FAST was 0.77 [95% CI (0.64–0.86)], specificity was 0.60 [95% CI (0.38–0.78)], the area under the ROC curve was 0.76, and the diagnostic ratio was 1.57, while the sensitivity of BEFAST was 0.68 [95% CI (0.23–0.93)], specificity was 0.85 [95% CI (0.72–0.92)], the area under the ROC curve was 0.86, and the diagnostic odds ratio was 2.44. No publication bias was detected in Deeks' funnel plot. For FAST, meta-regression analysis showed that the prospective design, satisfactory description of the index test, and a broad spectrum of disease contributed to the heterogeneity in sensitivity, while no sources contributed to the heterogeneity in sensitivity. When the pretest probability was set as 20%, the posterior probability in Fagan's Nomogram was 32%; however, when the pretest probability was set as 20% in BEFAST, the posterior probability in Fagan's Nomogram was 52%.ConclusionsOur findings indicated that FAST and BEFAST might be useful in the diagnosis of acute ischemic stroke. The diagnostic value of BEFAST in acute ischemic stroke was higher than in FAST; thus, it might have an important role in the fast recognition of acute ischemic stroke.

Background: Many meta-analyses (MAs) on Chinese medicine (CM) as an adjunctive treatment for gastric cancer have been published in recent years. However, the pooled evidence reported in MAs and their methodological quality remain unknown. Therefore, we designed a study to comprehensively evaluate and summarize the current evidence of CMs for gastric cancer in published MAs.Methods: A systematic search on MAs published in English from inception to 1st September 2021 was conducted in PubMed and Embase. The AMSTAR-2 tool was used to evaluate the methodological quality of the included MAs, and the results of the quality assessment were visualized using the evidence mapping method. Stata 17/SE was used for statistical analysis (Registration number: INPLASY202190005).Results: A total of 20 MAs (16 pairwise and 4 network MAs) were included from 118 records. These MAs were published in 14 journals from 2013 to 2021, with the number of patients and trials ranging from 688 to 6,857, and from 10 to 85, respectively. A large number of CMs (e.g., AiDi, FuFangKuShen, and HuaChanSu) in combination with chemotherapy for gastric cancer were identified among the included MAs. According to the pooled results reported in MAs, when compared to chemotherapy alone, CMs in combination with chemotherapy not only improve various outcomes on efficacy (e.g., objective response rate, quality of life) but also reduce various adverse reactions (e.g., leucopenia, nausea and vomiting). Only 2 MAs were low in terms of the overall methodological quality, while the other 18 MAs were all critically low. The methodology was required to be advanced significantly, mainly involving: study protocol and registration, explanation for the inclusion of study design, list of excluded studies with justifications, adequate details of included studies, reporting on funding sources of primary studies, and evaluation of the potential impact of risk of bias. In addition, MAs that received funds support (β = 2.68; 95%CI: 0.40 to 4.96; p = 0.024) or were published in journals with higher impact factor (β = 2.81; 95%CI: 0.69 to 4.92; p = 0.012) had a higher score on the overall methodological quality in the univariate analysis, but the results were not statistically significant according to the multivariate analysis.Conclusion: Combining CMs with chemotherapy can potentially improve clinical outcomes and reduce the relevant adverse effects in patients with gastric cancer. However, the methodological quality of relevant MAs requires significant improvement, and the current evidence needs to be validated through multinational trials that are well-designed and have a large sample size.

It is crucial to design efficient adsorbents for uranium from natural seawater with wide adaptability, effectiveness, and environmental safety. Porous organic polymers (POPs) provide superb tunable porosity and stability among developed porous materials. In this work, two new POPs, i.e., HCCP-P5-1 and HCCP-P5-2 were rationally designed and constructed by linked with macrocyclic pillar[5]arene as the monomer and hexachlorophosphate as the core via a macrocycle-to-framework strategy. Both pillar[5]arene-containing POPs exhibited high uranium adsorption capacity compared with previously reported macrocycle-free counterparts. The isothermal adsorption curves and kinetic studies showed that the adsorption of POPs on uranium was consistent with the Langmuir model and the pseudo-second-order kinetic model. Especially, HCCP-P5-1 has reached 537.81 mg/g, which is greater than most POPs that have been reported. Meanwhile, the comparison between both HCCP-P5-1 and HCCP-P5-2 can illustrate that the adsorption capacity and stability could be adjusted by the monomer ratio. This work provides a new idea for the design and construction of uranium adsorbents from macrocycle-derived POPs.

Objective: Different culprit plaque phenotypes including plaque rupture (PR) and non-plaque rupture (NPR), and N-Terminal prohormone of brain natriuretic peptide (NT-proBNP) have been reported to influence clinical outcomes in patients with acute coronary syndrome (ACS). We aimed to investigate the prognostic implication of the peak and baseline values at admission for NT-proBNP for major adverse cardiovascular events (MACE) in ST-Segment Elevated Myocardial Infarction (STEMI) patients with different plaque phenotype. Methods: A total of 428 patients with STEMI undergoing optical coherence tomography (OCT) were enrolled and divided into four groups: PR/Tertile1-2 NT-proBNP (n = 132), PR/Tertile3 NT-proBNP (n = 65), NPR/Tertile1-2 NT-proBNP (n = 154), NPR/Tertlie3 NT-proBNP (n = 77). Baseline and Peak values of NT-proBNP were obtained in the admission period. The MACEs were defined as the composite of all-cause death, recurrence of myocardial infarction and stroke. Results: High levels for peak NT-proBNP were significantly associated with a higher incidence of MACE and death (Log rank p = 0.037 and 0.0012, respectively). In the subgroup with NPR, a high level for peak NT-proBNP was significantly associated with higher incidence of death (Log rank p = 0.0022) but this association was not significant in the subgroup of PR (Log rank p = 0.24). Though plaque types were not associated with adverse event, the combination of NPR and a higher peak value for NT-proBNP indicated higher incidence of death compared with other groups (Log rank p = 0.0017). The area under the receiver operating characteristic curve for predicting death to evaluate the diagnostic value of the peak value for NT-proBNP and plaque types combined with traditional risk factors was 0.843 (95% CI: 0.805–0.876), which is superior to solely traditional risk factors: NRI (26.8% [95% CI: 0.4–53.1%], p = 0.046) and IDI (5.1% [95% CI: 1.0–9.2%], p = 0.016). Conclusion: STEMI patients with NPR and a high level for peak NT-proBNP showed higher incidence of death. The peak value of NT-proBNP in combination with plaque types can be used in risk stratification and prediction of death in patients with STEMI.

This study aimed to investigate the association between changes in levels of trimethylamine N-oxide (TMAO) and its precursors and the prognosis of patients with acute myocardial infarction (AMI). Patients diagnosed with AMI were prospectively enrolled at Fuwai Hospital between March 2017 and January 2020. TMAO, betaine, choline, and L-carnitine were measured in 1203 patients at their initial admission and 509 patients at their follow-up of one month. Major adverse cardiovascular events (MACE), a composite of all-cause death, recurrence of MI, rehospitalization caused by HF, ischemic stroke, and any revascularization, were followed up. A decision tree by TMAO levels implicated that compared to those with low levels at admission, patients with high TMAO levels at both time points showed an increased risk of MACE (adjusted hazard ratio (HR) 1.59, 95% confidence interval (CI): 1.03–2.46; p = 0.034), while patients with high TMAO levels at admission and low levels at follow-up exhibited a similar MACE risk (adjusted HR 1.20, 95% CI: 0.69–2.06; p = 0.520). Patients with high choline levels at admission and follow-up showed an elevated MACE risk compared to those with low levels at both time points (HR 1.55, 95% CI: 1.03–2.34; p = 0.034). Repeated assessment of TMAO and choline levels helps to identify the dynamic risk of cardiovascular events.

Background. In vivo studies show that LL-37 inhibits the progression of atherosclerosis and predicts a lower risk of recurrent ischemia in patients with acute myocardial infarction (AMI), which could be mediated by the modulation of lipid metabolism. The current study aimed to investigate the effects of various lipid contents on the prognostic impacts of LL-37 in patients with AMI. Methods. A total of 1567 consecutive AMI patients were prospectively recruited from March 2017 to January 2020. Patients were firstly stratified into two groups by the median level of LL-37 and then stratified by levels of various lipid contents and proprotein convertase subtilisin/kexin type 9 (PCSK9). Cox regression with multiple adjustments was performed to analyze associations between LL-37, lipid profiles, PCSK9, and various outcomes. The primary outcome was major adverse cardiovascular event (MACE), a composite of all-cause death, recurrent MI, and ischemic stroke. Results. During a median follow-up of 786 (726–1107) days, a total of 252 MACEs occurred. A high level of LL-37 was associated with lower risk of MACE in patients with elevated lipoprotein(a) (≥300 mg/L, hazard ratio (HR): 0.49, 95% confidence interval (CI): 0.29–0.86, p = 0.012) or PCSK9 levels above the median (≥47.4 ng/mL, HR: 0.57, 95% CI: 0.39–0.82, p < 0.001), which was not observed for those without elevated lp(a) (p = 0.781, pinteraction = 0.035) or PCSK9 (p = 0.905, pinteraction = 0.032). Conclusions. For patients with AMI, a high level of LL-37 was associated with lower ischemic risk among patients with elevated lp(a) and PCSK9.

BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. However, the roles of TILs, TLS, and their correlation in Epstein-Barr Virus-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) are largely unknown.MethodsTo observe the correlation among TILs, TLS, and clinicopathological characteristics and their prognostic significance in EBVaGC and EBVnGC, respectively. TILs and TLS were assessed by morphology and/or immunohistochemistry, and accompanied by clinicopathological analysis from 846 gastric cancer patients in multiple institutions.ResultsForty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by in situ hybridization, respectively. For EBVnGC, higher TILs grade was correlated with TLS-present. EBVnGC patients with high TILs grade and TLS-present exhibited survival benefits. TILs (P = 0.001) and TLS (P = 0.003), especially TILs & TLS (P < 0.001) were independent prognostic factors in EBVnGC. A nomogram was constructed and validated for predicting the probability of overall survival and performed well with a good calibration. No significant prognostic value was detected in EBVaGC.ConclusionTILs and TLS, especially TILs & TLS were promising prognostic indicators for overall survival in EBVnGC. TILs and TLS were highly overlapping in their extent and prognostic abilities, and may be considered as a coindicator of prognosis of gastric cancer. The evaluations of TILs and TLS are simple and can be assessed routinely in pathological diagnosis.

Background: This study compared differences in the risk factors and clinical outcomes of primary percutaneous coronary intervention (PCI) in type 2 diabetes mellitus (DM) and non-DM patients with de novo lesions (DNLs) and late or very late stent thrombosis (LST/VLST).Methods: We used angiography to screen 4,151 patients with acute coronary syndrome for DNL and LST/VLST lesions. Overall, 3,941 patients were included in the analysis and were allocated to the DM (n = 1,286) or non-DM (n = 2,665) group at admission. The primary endpoint was a composite of major adverse cardiovascular events (MACEs), defined as death, myocardial infarction, revascularization, and ischemic stroke, within a median follow-up period of 698 days.Results: In the group with a total white blood cell count >10 × 109/L (P = 0.004), a neutral granular cell count >7 × 109/L (P = 0.030), and neutrophil–lymphocyte ratio >1.5 (P = 0.041), revascularization was better for DNL than for LST/VLST lesions. Among DM patients with DNLs, each unit increase in age was associated with a 53.6% increase in the risk of MACEs [hazard ratio (HR): 1.536, 95% confidence interval (CI), 1.300–1.815, P < 0.0001]. Older age (≥65 years) was associated with a significantly greater risk of MACEs (P < 0.0001). Furthermore, each standard deviation (SD) increase in the level of peak white blood cell counts was associated with a 50.1% increase in the risk of MACEs (HR, 1.501; 95% CI, 1.208–1.864; P = 0.0002). When stratifying the DM population with DNLs according to the D-dimer baseline and peak levels

In this paper, a type of novel composite structure coil applied in the coreless stator is proposed and studied to improve the output performance and efficiency of the axial flux permanent magnet (AFPM) machine. In which the effective conductor is changed to be wedge-shaped by the rolling technology so that the turns of coils and filling factor can be further increased, and the ends are kept in the cylinder with a larger diameter to reduce the DC copper loss. Meanwhile, the air region between the double rotors of the machine is also modified to be wedge-shaped, which fully matches the proposed coils and shortens the air gap length. The advantages of performance can be verified by the three-dimensional (3D) finite element analysis (FEA) and analytical method so that the output characteristics of no-load and load can be improved, and the DC copper loss and eddy current loss of coils can be reduced. The coreless AFPM machine finally performs a high efficiency of 95.34% according to these valuable optimizations.

The presence of calcified plaques is one of the pathological phenotypes of acute coronary syndrome (ACS) and can be frequently found in culprit lesion segments. Trimethylamine N-oxide (TMAO) is reported to be involved in vascular calcification and plaque instability. This study investigated the relationship between plasma TMAO levels and calcified lesions in culprit lesion segments in STEMI patients. A prospective series of 179 patients with STEMI were enrolled, and calcified lesions from 127 patients were analyzed by OCT. The plasma TMAO levels were measured by using stable isotope dilution liquid chromatography tandem mass spectrometry. Patients were divided into two groups according to the median plasma TMAO level. The prevalence of intimal calcified lesions in the high TMAO group was significantly higher than that in the low TMAO group (90.6 vs. 57.1%, p < 0.001; 84.4 vs. 44.4%, p < 0.001). After adjustment of traditional risk factors and medication history, patients with calcification in their culprit lesion segments had higher plasma TMAO levels than those without calcification. Moreover, plasma TMAO levels were significantly positively associated with the parameters of calcium burden, including maximal calcification arc (r = 0.392, p < 0.001), maximal calcification thickness (r = 0.443, p < 0.001), and calcified length (r = 0.466, p < 0.001). These results suggested that the level of TMAO is significantly correlated with the incidence of calcification in the culprit lesion segment, and the measurement of TMAO levels might improve clinical management in patients with heavy calcification.Clinical Trial Registration: This study is registered at ClinicalTrials.gov as NCT03593928.

Background: Bilirubin, a natural product of heme catabolism, has antioxidant and anti-inflammatory activities and is inversely associated with stable coronary artery disease. However, the relationship between the bilirubin levels and long-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI) remains unknown. This study aimed to establish a score model based on bilirubin for predicting major adverse cardiovascular events (MACEs) and stratify patients to the level of care.Methods and Results: Data of 4,151 consecutive patients with STEMI who underwent PPCI were evaluated, and 3,708 cases were analyzed. The total bilirubin (TBil) levels were measured during admission, and the study population was divided into two groups. The high TBil group (n = 143) comprised patients who had a TBil level of ≥22 μmmol/L, and the low TBil group (n = 3,565) comprised patients who had a TBil level of

Background: The population with myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PPCI) is growing, but validated models to guide their clinical management are lacking. This study aimed to develop and validate prognostic models to predict major adverse cardiovascular events (MACEs) in patients with MI undergoing PPCI.Methods and Results: Models were developed in 4,151 patients with MI who underwent PPCI in Fuwai Hospital between January 2010 and June 2017, with a median follow-up of 698 days during which 544 MACEs occurred. The predictors included in the models were age, a history of diabetes mellitus, atrial fibrillation, chronic kidney disease, coronary artery bypass grafting, the Killip classification, ejection fraction at admission, the high-sensitivity C-reactive protein (hs-CRP) level, the estimated glomerular filtration rate, the d-dimer level, multivessel lesions, and the culprit vessel. The models had good calibration and discrimination in the derivation and internal validation with C-indexes of 0.74 and 0.60, respectively, for predicting MACEs. The new prediction model and Thrombolysis in Myocardial Infarction (TIMI) risk score model were compared using the receiver operating characteristic curve. The areas under the curve of the new prediction model and TIMI risk score model were 0.806 and 0.782, respectively (difference between areas = 0.024 < 0.05; z statistic, 1.718).Conclusion: The new prediction model could be used in clinical practice to support risk stratification as recommended in clinical guidelines.

For the design of printed circuit board (PCB) winding, it is necessary to take into account the requirements of electromagnetic and manufacture technology of PCB winding, which directly affect the output power of the machine. In this paper, for axial flux permanent magnet generator (AFPMG) of a small wind power system, the unequal-width (UEW) winding is proposed for the aim of improving the output power of the generator. The design ideas and methods of unequal-width (UEW) winding are proposed in combination with manufacture technology of the PCB. The finite element analysis (FEA) model of machine is built. The analytical formulas of electromotive force (EMF) and winding loss are derived. Though the comparisons between reactance and impedance of PCB winding, the analytical formula of output power is simplified. These characteristics of the generator with traditional equal-width(EW) winding and proposed UEW winding are analyzed and compared in detail by FEA and analytical calculation. The result shows that the output power of the generator with UEW winding is improved largely. Finally, the validity of the FEA model and analysis method is verified by experiment of prototype machine, which provides the reference for the design of AFPMG with PCB winding.

Lifestyle modifications are recommended as the initial treatment for high blood pressure. The influence of dyslipidemia might be via moderate arterial stiffness, which results in hypertension and cardiovascular disease. We used data from a subgroup of the lifestyle, level of serum lipids/carotid femoral-pulse wave velocity (CF-PWV) Susceptibility BEST Study, a population-based study of community-dwelling adults aged 45–75 years. The serum lipid level and CF-PWV were measured at baseline, and lifestyle such as smoking status, sleeping habits, and the level of oil or salt intake was determined with the use of a validated questionnaire during follow-up. Arterial stiffness was determined as CF-PWV using an electrocardiogram after a mean follow-up of 4.4 years. Regression coefficients (95% CIs), adjusted for demographics, risk factors, cholesterol, and triglycerides (TGs), were calculated by linear regression. Logistic regression analysis was used to identify the association between the variables with CF-PWV independently. In the results, glucose and total cholesterol (TC) were associated with higher CF-PWV (p = 0.000) and lower-destiny lipoprotein was associated with lower CF-PWV (p = 0.001) after adjustments for age, sex, mean arterial pressure, and heart rate. There were significant associations observed for current salt intake in relation to CF-PWV (p-trend = 0.038) without adjustment. This association was retained after adjustments for covariates and had statistical significance (p-trend = 0.048) in model 3, which adjusted age, sex, baseline CF-PWV, mean arterial pressure, heart rate waist circumference, education, smoking status, physical activity, diabetes mellitus (DM), heart disease, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, TGs, antihypertensive medicine, nitrate medicine, and antiplatelet medicine. Linear regression showed statistically significant associations between LDL and CF-PWV in the fully adjusted models (model 1 p = 0.010, model 2 p = 0.020, model 3 p = 0.017). Logistic regression analysis showed that CF-PWV was independently associated with age (p = 0.000), TC (p = 0.000), TGs (p = 0.000), and homo-cysteine (p = 0.000), and their odds ratios were 0.781, 3.424, 0.075, and 1.046, respectively. Our results showed a positive association between LDL and arterial stiffness, and suggested that less smoking status, sleeping disorder, and salt intake were associated with less arterial stiffness.