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IntroductionKawasaki disease (KD) is a medium-vessel vasculitis predominantly affecting children under 5 years of age and may involve the coronary arteries.MethodsA mouse KD model was induced by Candida albicans cell wall extracts (CAWS), cardiac tissues were analyzed through integrated lactylomic and proteomic profiling. The lysine lactylation (Kla) results were normalized to the proteomic data.ResultsElevated serum lactate and lactate dehydrogenase (LDH) levels were observed in KD patients. Given lactate’s role as a substrate for Kla, this study investigated Kla modifications in KD. Proteomic analysis identified 150 upregulated proteins and 18 downregulated proteins, with 38.1% located in the cytoplasm and significant enrichment in immune-related pathways. After normalization, 41 sites in 37 proteins were found to be upregulated in the Kla data, with no downregulated sites. Approximately 67.57% of the altered proteins were localized in the mitochondria. Bioinformatics analysis indicated alterations in aerobic respiration, energy production and conversion, and key immune- and metabolism-related pathways.DiscussionThis study enhances the understanding of Kla modifications in the development of KD and may inform targeted therapies for its prevention and improved prognosis.

BackgroundA liver abscess caused by hypervirulent Klebsiella pneumoniae can lead to multiple invasive extrahepatic infections, including lung abscesses, endophthalmitis, brain abscesses, and necrotizing fasciitis. This condition, known as Klebsiella pneumoniae liver abscess invasion syndrome, progresses rapidly and is associated with severe illness, high disability rates, and significant mortality. However, bloodstream infections with co-infection involving carbapenem-resistant Acinetobacter baumannii are exceedingly rare.Case presentationThe Emergency Medicine Department of the First People’s Hospital of Kunshan successfully treated a male patient diagnosed with liver, lung, and prostate abscesses. The patient underwent puncture and drainage, with analysis of the drainage fluid, sputum culture, and metagenomic next-generation sequencing (m-NGS) revealing a co-infection with blood-borne Klebsiella pneumoniae and Acinetobacter baumannii. Guided by drug sensitivity test results, the patient received treatment with polymyxin and cefoperazone sodium-sulbactam sodium for infection control and liver protection. The treatment was successful, and the patient fully recovered and was discharged.ConclusionBy reporting this rare case and highlighting the drug resistance of the bacteria, we propose a new diagnosis and treatment plan for managing Klebsiella pneumoniae combined with carbapenem-resistant Acinetobacter baumannii infection, along with a literature review.

BackgroundsFunctional near-infrared spectroscopy (fNIRS) is widely used for the evaluation of mental workload (MWL), but it is not yet clear whether it is affected by physical factors during cognitive tasks. Therefore, the combined effects of physical and cognitive loads on hemodynamic features in the prefrontal cortex were evaluated.MethodsThirty-three eligible healthy male subjects were asked to perform three types of cognitive tasks (1-back, 2-back and 3-back). Concurrently, isotonic contraction aerobic exercise of the left upper limb was added. During this compound task, fNIRS signals, workload perception and task performance were recorded. Based on the oxyhemoglobin concentration, Pearson’s correlation coefficient (CORR), coherence value (COH) and the phase-locking value (PLV) were calculated to reflect FC among eight channels.ResultsOn the basis of effects of cognitive tasks, the concurrent physical activities would further increase National Aeronautics and Space Administration Task Load Index score (p

Traumatic Renal Artery Thrombosis (TRAT) is an uncommon condition characterized by a low clinical incidence and a lack of specific symptoms, making it highly susceptible to being overlooked or misdiagnosed. This retrospective analysis aims to review the diagnostic and therapeutic approaches applied to a TRAT patient who received successful treatment in the Emergency Medicine Department of the First People’s Hospital of Kunshan. The objective is to enhance clinicians’ comprehension of TRAT, promote early diagnosis and intervention, and ultimately improve patient outcomes.

Negative pressure pulmonary edema (NPPE) is a form of non-cardiogenic pulmonary edema triggered by a swift increase in negative intrapleural pressure due to upper airway obstruction and represents a potential cause of acute respiratory failure. This study documents a case of NPPE post-endotracheal extubation subsequent to general anesthesia. The patient, a young female, underwent a “laparoscopy-assisted unilateral salpingectomy” under general anesthesia for an ectopic pregnancy. Immediately post-extubation, the patient exhibited a sudden decline in oxygen saturation and tachypnea. Pink frothy secretions were suctioned from the oral and nasal cavities. Swift interventions, including oxygen therapy, non-invasive ventilation, diuretics, and corticosteroids, were administered. The patient’s condition was effectively managed, and after 6 days of treatment, she was discharged from the hospital following full recovery.

This study investigated the impact of transcutaneous electrical acupoint stimulation (TEAS) at Neiguan acupoint (PC6) on the physiological and behavioral responses of participants exposed in virtual height. 40 participants were included in the study and were randomly assigned to either a control group or an intervention group. Participants had an immersive experience with a VR interactive platform that provided somatosensory interaction in height stimulation scenes. Psychological scores, behavioral and cognitive performance, and physiological responses were recorded and analyzed. The results indicated that the intervention group had significantly lower fear scores compared to the control group. Analysis of heart rate variability revealed that the intervention group exhibited improved heart rate variability, indicating enhanced cardiovascular function and emotion regulation. The behavioral and cognitive results demonstrated that the intervention group exhibited higher left eye openness, faster reaction times, and greater movement distance, suggesting enhanced attentional focus, cognitive processing, and reduced avoidance behaviors. These findings suggest that TEAS at PC6 can effectively reduce fear and improve the regulation of physiological and behavioral responses to negative emotional stimuli.

Previous neuroimaging studies have revealed abnormal brain networks in patients with major depressive disorder (MDD) in emotional processing. While any cognitive task consists of a series of stages, little is yet known about the topology of functional brain networks in MDD for these stages during emotional face recognition. To address this problem, electroencephalography (EEG)-based functional brain networks of MDD patients at different stages of facial information processing were investigated in this study. First, EEG signals were collected from 16 patients with MDD and 18 age-, gender-, and education-matched normal subjects when performing an emotional face recognition task. Second, the global field power (GFP) method was employed to divide group-averaged event-related potentials into different stages. Third, using the phase transfer entropy (PTE) approach, the brain networks of MDD patients and normal individuals were constructed for each stage in negative and positive face processing, respectively. Finally, we compared the topological properties of brain networks of each stage between the two groups using graph theory approaches. The results showed that the analyzed three stages of emotional face processing corresponded to specific neurophysiological phases, namely, visual perception, face recognition, and emotional decision-making. It was also demonstrated that depressed patients showed abnormally decreased characteristic path length at the visual perception stage of negative face recognition and normalized characteristic path length in the stage of emotional decision-making during positive face processing compared to healthy subjects. Furthermore, while both the MDD and normal groups’ brain networks were found to exhibit small-world network characteristics, the brain network of patients with depression tended to be randomized. Moreover, for patients with MDD, the centro-parietal region may lose its status as a hub in the process of facial expression identification. Together, our findings suggested that altered emotional function in MDD patients might be associated with disruptions in the topological organization of functional brain networks during emotional face recognition, which further deepened our understanding of the emotion processing dysfunction underlying MDD.

Backgrounds: The validity of heart rate variability (HRV) has been substantiated in mental workload assessments. However, cognitive tasks often coincide with physical exertion in practical mental work, but their synergic effects on HRV remains insufficiently established. The study aims were to investigate the combined effects of cognitive and physical load on autonomic nerve functions.Methods: Thirty-five healthy male subjects (aged 23.5 ± 3.3 years) were eligible and enrolled in the study. The subjects engaged in n-back cognitive tasks (1-back, 2-back, and 3-back) under three distinct physical conditions, involving isotonic contraction of the left upper limb with loads of 0 kg, 3 kg, and 5 kg. Electrocardiogram signals and cognitive task performance were recorded throughout the tasks, and post-task assessment of subjective experiences were conducted using the NASA-TLX scale.Results: The execution of n-back tasks resulted in enhanced perceptions of task-load feelings and increased reaction times among subjects, accompanied by a decline in the accuracy rate (p < 0.05). These effects were synchronously intensified by the imposition of physical load. Comparative analysis with a no-physical-load scenario revealed significant alterations in the HRV of the subjects during the cognitive task under moderate and high physical conditions. The main features were a decreased power of the high frequency component (p < 0.05) and an increased low frequency component (p < 0.05), signifying an elevation in sympathetic activity. This physiological response manifested similarly at both moderate and high physical levels. In addition, a discernible linear correlation was observed between HRV and task-load feelings, as well as task performance under the influence of physical load (p < 0.05).Conclusion: HRV can serve as a viable indicator for assessing mental workload in the context of physical activities, making it suitable for real-world mental work scenarios.

Acute poisoning is a significant public health concern. This retrospective study investigates trends in acute poisoning cases and explores the clinical and sociodemographic profiles associated with this condition. Medical data from 859 hospitalized patients diagnosed with acute poisoning between January 2017 and December 2022 were comprehensively analyzed. The descriptive statistical analysis revealed that 360 patients had underlying diseases, with depression being the most prevalent among them. Furthermore, urban areas accounted for 87.2% of the acute poisoning cases, indicating a higher incidence compared to rural areas. The substances implicated in acute poisoning incidents varied, with drugs of abuse being the most common (53.2%), followed by pesticides (22.2%), carbon monoxide (11.8%), and alcohol (5.4%). Suicide attempt/suicide emerged as the leading cause of acute poisoning incidents, accounting for 75.9% of cases, while poisoning accidents predominantly occurred within the home setting. Through chi-square tests, it was determined that risk factors for suicide attempt/suicide included female gender and underlying medical conditions. Temporal analysis showed that the total number of acute poisoning cases increased from 2017 to 2019 and decreased from 2019 to 2022. Notably, suicide-related cases exhibited an upward trend, with suicide attempt/suicide accounting for over 80% of all acute poisoning cases after 2020. This study contributes valuable insights into the trends, profiles, and risk factors associated with acute poisoning cases.

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10–20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.

Aims: Gut-microbiome derived short-chain fatty acids exert anti-inflammatory effects and delay progression of kidney disease in diabetic nephropathy. The aim of this study was to examine the impact in vivo and in vitro of short-chain fatty acid treatment on cellular pathways involved in the development of experimental diabetic nephropathy.Methods: To determine the effect of short-chain fatty acids in diabetic nephropathy, we compared wildtype, GPR43−/− and GPR109A−/− mice diabetic mice treated with acetate or butyrate and assessed variables of kidney damage. We also examined the impact of short-chain fatty acid treatment on gene expression in renal tubular cells and podocytes under high glucose conditions.Results: Short-chain fatty acid treatment with acetate or butyrate protected wild-type mice against development of diabetic nephropathy, exhibiting less glomerular hypertrophy, hypercellularity and interstitial fibrosis compared to diabetic controls. Acetate and butyrate treatment did not provide the same degree of protection in diabetic GPR43−/− and GPR109A−/− diabetic mice respectively. Consistent with our in vivo results, expression of pro-inflammatory genes in tubular epithelial cells exposed to high glucose were attenuated by acetate and butyrate treatment. Acetate did not reduce inflammatory or fibrotic responses in glucose stimulated GPR43−/− TECs. Butyrate mediated inhibition of pro-fibrotic gene expression in TECs through GPR109A, and in podocytes via GPR43.Conclusion: SCFAs protect against progression of diabetic nephropathy and diminish podocyte and tubular epithelial injury and interstitial fibrosis via direct, GPR-pathway dependent effects on intrinsic kidney cells. GPR43 and GPR109A are critical to short-chain fatty acid mediated reno-protection and have potential to be harnessed as a therapeutic target in diabetic nephropathy.

BackgroundChimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity.MethodsThis study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers.ResultsWe found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion.ConclusionsOur results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis.

AimsThe Ca+/NFAT (Nuclear factor of activated T cells) signaling pathway activation is implicated in the pathogenesis of Kawasaki disease (KD); however, we lack detailed information regarding the regulatory network involved in the human coronary endothelial cell dysfunction and cardiovascular lesion development. Herein, we aimed to use mouse and endothelial cell models of KD vasculitis in vivo and in vitro to characterize the regulatory network of NFAT pathway in KD.Methods and ResultsAmong the NFAT gene family, NFAT2 showed the strongest transcriptional activity in peripheral blood mononuclear cells (PBMCs) from patients with KD. Then, NFAT2 overexpression and knockdown experiments in Human coronary artery endothelial cells (HCAECs) indicated that NFAT2 overexpression disrupted endothelial cell homeostasis by regulation of adherens junctions, whereas its knockdown protected HCAECs from such dysfunction. Combined analysis using RNA-sequencing and transcription factor (TF) binding site analysis in the NFAT2 promoter region predicted regulation by Forkhead box O4 (FOXO4). Western blotting, chromatin immunoprecipitation, and luciferase assays validated that FOXO4 binds to the promoter and transcriptionally represses NFAT2. Moreover, Foxo4 knockout increased the extent of inflamed vascular tissues in a mouse model of KD vasculitis. Functional experiments showed that inhibition NFAT2 relieved Foxo4 knockout exaggerated vasculitis in vivo.ConclusionsOur findings revealed the FOXO4/NFAT2 axis as a vital pathway in the progression of KD that is associated with endothelial cell homeostasis and cardiovascular inflammation development.

AimThe purpose of this study was to evaluate the effectiveness of the graded transport mode in the intrahospital transport (IHT) of critically ill patients.MethodsThis is a retrospective study, including 800 patients and categorized them into control and observation groups. The control group included 420 critically ill patients who were transported via conventional methods from our emergency resuscitation unit from June 2017 to December 2017. The observation group included 380 critically ill patients who were transported through a graded transport mode from January 2018 to June 2018. We performed intergroup comparisons of the incidence rates and causes of adverse events (AEs), transport time, length of stay, and mortality rate.ResultsThe observation group had significantly lower transport time and AE incidence rates than the control group. However, no significant differences were observed in terms of the length of stay and mortality rate between the two groups.ConclusionThe most notable merits of the graded transport mode in the IHT of critical care patients include the fact that it significantly reduces the incidence of AEs during IHT, shortens the transport time, and improves transport efficiency, thereby ensuring the safety of critically ill patients.

IntroductionA contactless multiscale cardiac motion measurement method is proposed using impulse radio ultra-wideband (IR-UWB) radar at a center frequency of 7.29 GHz.MotivationElectrocardiograph (ECG), heart sound, and ultrasound are traditional state-of-the-art heartbeat signal measurement methods. These methods suffer from defects in contact and the existence of a blind information segment during the cardiogram measurement.MethodsExperiments and analyses were conducted using coarse-to-fine scale. Anteroposterior and along-the-arc measurements were taken from five healthy male subjects (aged 25–43) when lying down or prone. In every measurement, 10 seconds of breath-holding data were recorded with a radar 55 cm away from the body surface, while the ECG was monitored simultaneously as a reference.ResultsCardiac motion detection from the front was superior to that from the back in amplitude. In terms of radar detection angles, the best cardiac motion information was observed at a detection angle of 120°. Finally, in terms of cardiac motion cycles, all the ECG information, as well as short segments of cardiac motion details named blind ECGs segments, were detected.SignificanceA contactless and multiscale cardiac motion detection method is proposed with no blind detection of segments during the entire cardiac cycle. This paves the way for a potentially significant method of fast and accurate cardiac disease assessment and diagnosis that exhibits promising application prospects in contactless online cardiac monitoring and in-home healthcare.

ObjectiveSerum inflammatory biomarkers play crucial roles in the development of acute ischemic stroke (AIS). In this study, we explored the association between inflammatory biomarkers including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), and clinical outcomes in AIS patients who achieved successful recanalization.MethodsPatients with AIS who underwent endovascular thrombectomy (EVT) and achieved a modified thrombolysis in the cerebral infarction scale of 2b or 3 were screened from a prospective cohort at our institution between January 2013 and June 2021. Data on blood parameters and other baseline characteristics were collected. The functional outcome was an unfavorable outcome defined by a modified Rankin Scale of 3–6 at the 3-month follow up. Other clinical outcomes included symptomatic intracranial hemorrhage (sICH) and 3-month mortality. Multivariable logistic regression analysis was performed to evaluate the effects of PLR, NLR, and MLR on clinical outcomes.ResultsA total of 796 patients were enrolled, of which 89 (11.2%) developed sICH, 465 (58.4%) had unfavorable outcomes at 3 months, and 168 (12.1%) died at the 3-month follow up. After adjusting for confounding variables, a higher NLR (OR, 1.076; 95% confidence interval [CI], 1.037–1.117; p < 0.001) and PLR (OR, 1.001; 95%CI, 1.000–1.003; p = 0.045) were significantly associated with unfavorable outcomes, the area under the receiver operating characteristic curve of NLR and PLR was 0.622 and 0.564, respectively. However, NLR, PLR, and MLR were not independently associated with sICH and 3-month mortality (all adjusted p > 0.05).ConclusionOverall, our results indicate that higher PLR and NLR were independently associated with unfavorable functional outcomes in AIS patients with successful recanalization after EVT; however, the underlying mechanisms are yet to be elucidated.

Introduction: To explore the mechanism of action of appling Radix Ginseng and Semen Ziziphi Spinosae Drug pair (R-S) in the treatment of insomnia by investigating the effect of R-S on GLU/GABA-GLN metabolic cycle and intestinal microflora of rats with insomnia.Methods: Rats were intraperitoneally injected with 4-chloro-DL-phenylalanine (PCPA) to make sleep deprivation (SD) models. The rats were divided into 6 groups, with 8 rats in each group. The general status of the rats was observed and the pentobarbital sodium sleep synergy experiment was performed. The contents of GABA, GLU, GLN, GAD65, and GS in hippocampus of rats were determined by ELISA. The expressions of GABAARα1mRNA, mGluR5mRNA, NR1mRNA and GluR1mRNA in rats’ hippocampal tissue were determined by Realtime PCR. 16SrRNA gene sequencing was used to analyze the intestinal microflora of insomnia rats.Results: In PCPA-induced insomnia rats, the state of insomnia was relieved, the sleep rate was improved, the duration of sleep latency was shortened and the sleep duration was prolonged in each dose group of R-S (p < 0.05, p < 0.01) compared with the model group. The contents of GABA, GLN, GAD65 and GS were increased (p < 0.05, p < 0.01) while GLU content was decreased (p < 0.01) in both medium and high dose groups, especially in the high dose group. The expression of GABAARα1mRNA was increased (p < 0.01), and the expressions of mGluR5mRNA, NR1mRNA and GluR1mRNA were decreased (p < 0.01) in hippocampal tissue of rats in R-S groups, especially in the high dose group. At the same time, the various dose groups of R-S could improve the species diversity, microflora abundance of insomnia rats and regulate the KEGG metabolic pathway related to sleep.Discussion: R-S can improve the sleep of PCPA-induced insomnia rats by regulating GLU/GABA-GLN metabolic cycle and intestinal microflora, which provides experimental basis for appling R-S in the treatment of insomnia.

BackgroundDepression and type 2 diabetes (T2D) are serious public health problems with irreversible health consequences and a significant economic burden on the healthcare system. Previous studies have suggested that blood urea nitrogen (BUN) was inversely longitudinally associated with incidence of diabetes and depression in adults, but few well-designed studies have examined the effects of status of T2D on the full range of relationship between BUN and depression.MethodsThe analysis sample consisted of adults aged≥20 years from the 2007-2014 National Health and Nutrition Examination Survey (NHANES) who completed the Patient Health Questionnaire-9 (PHQ–9), involving 19,005 participants. By stratifying participants according to T2D status, we further assessed the difference between BUN and risk of depression in participants with and without T2D using multivariate logistic regression (interaction test).ResultsIn this cross-sectional study, the association between BUN and depression prevalence appeared to differ between the T2D and non-T2D groups (OR: 1.00, 95% Cl: 0.95-1.05 vs. OR: 0.89, 95% Cl: 0.85-0.93). In addition, there was evidence of an interaction between BUN levels and T2D status in reducing the risk of depression (P value for interaction = 0.032.) The relationship between BUN and depressive symptoms was significant in non-T2D subjects (P < 0.001), but not in T2D (P = 0.940).ConclusionsOur findings suggest that there is a significant relationship between BUN and depression, and T2D status may influence the association between BUN and the risk of depression. Such findings require further prospective studies to provide more evidence.

Lagerstroemia indica has great economic value due to its ecological, medicinal, and ornamental properties. Because its bloom color is one of the most essential characteristics, research into its color development is a hot topic. In this study, five representative colored cultivars were chosen, each representing a different color, such as white, red, pink, violet, and purple. Fully bloomed flowers were used to detect flavonoids in the petals. Anthocyanin is the main factor for the color formation of L. indica. 14 anthocyanins were discovered among the 299 flavonoids. Among 14 anthocyanins, malvidin-3,5-di-O-glucoside varied greatly among four colored samples and is the main contributor to color diversity. Transcriptome sequencing revealed that compared to white flowers, Anthocyanin pathway genes appear to be more active in colored samples. Analyzing the correlation network between metabolites and differential expressed genes, 53 key structural genes, and 24 TFs were detected that may play an essential role in the formation of color in L. indica flowers. Among these, the differential expression of F3′5′H and F3′H between all samples are contributors to color diversity. These findings lay the foundation for discovering the molecular mechanism of L. indica flower color diversity.

A prolonged period of vigilance task will lead to vigilance decrement and a drop in cognitive efficiency. Although transcranial direct current stimulation (tDCS) can be used to improve cognitive performance following vigilance decrement, the findings in this area of study are inconsistent. This study aims to identify the neuroelectrophysiological and behavioral effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) on executive vigilance under a continuous monotonous condition. We recruited 29 participants who randomly received 30 min active or sham tDCS before the vigilance task (anode electrode at the left DLPFC, cathode electrode at the right supraorbital area). Participants completed four sessions of vigilance task and five sessions of self-report sleepiness, Oddball task, and Go/Nogo task, for a total of about 5 h. EEG was acquired in real-time throughout the experiment. Repeated measures of ANOVA were utilized to analyze the evolution of each metric with task-on-time. The results demonstrated that subjective arousal state, vigilance performance, event-related potentials (ERPs), and EEG power were significantly affected by time on task. Brain stimulation did not significantly affect the evolution of subjective and objective executive vigilance performance, but significantly modulated spontaneous activity in the alpha and beta bands across the entire brain. The continuous enhancement of the prefrontal cortex increased P2 amplitude for the Oddball task, which was associated with the enhancement of the early stage of information processing. P3 amplitude had a temporary enhancement effect, which significantly decreased following a cognitive fatigue. tDCS had a continuous enhancement effect on N2 amplitude for the Go/Nogo task, which was associated with the enhanced inhibition of distracting stimuli. Together, the current data suggest that anodal tDCS over left DLPFC possibly enhances the early stage of relevant information processing and the inhibitory control of distracting stimuli during a continuous and monotonous vigilance task.

ObjectiveThis study aimed to develop and validate a nomogram to predict malignant cerebral artery infarction (MMI) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) in the modern thrombectomy era.MethodsWe retrospectively analyzed data from a prospective cohort of consecutive patients with AIS who underwent EVT at Xuanwu hospital between January 2013 and June 2021. A multivariable logistic regression model was employed to construct the nomogram for predicting MMI after EVT. The discrimination and calibration of the nomogram were assessed both in the derivation and validation cohorts.ResultsA total of 605 patients were enrolled in this study, with 425 in the derivation cohort and 180 in the validation cohort. The nomogram was developed based on admission systolic blood pressure (SBP), the National Institute of Health Stroke Score (NIHSS), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), vessel occlusion site, EVT time window, and recanalization status. The nomogram displayed good discrimination with the area under the receiver operating characteristics (ROCs) curve (AUC) of 0.783 [95% confidence interval (CI), 0.726–0.840] in the derivation cohort and 0.806 (95% CI, 0.738–0.874) in the validation cohort. The calibration of the nomogram was good as well, with the Hosmer–Lemeshow test of p = 0.857 in the derivation cohort and p = 0.275 in the validation cohort.ConclusionIn the modern thrombectomy era, a nomogram containing admission SBP, NIHSS, ASPECTS, vessel occlusion site, EVT time window, and recanalization status may predict the risk of MMI after EVT in patients with AIS.

Tree peony (Paeonia suffruticosa) is a traditional Chinese flower that is not resistant to high temperatures, and the frequent sunburn during summer limits its normal growth. The lack of understanding of the molecular mechanisms in tree peony has greatly restricted the improvement of novel heat-tolerant varieties. Therefore, we treated tree peony cultivar “Yuhong” (P. suffruticosa “Yuhong”) at normal (25°C) and high temperatures (40°C) and sequenced the transcriptomes, to investigate the molecular responsive mechanisms to heat stress. By comparing the transcriptomes, a total of 7,673 differentially expressed genes (DEGs) were detected comprising 4,220 upregulated and 3,453 downregulated genes. Functional annotation showed that the DEGs were mainly related to the metabolic process, cells and binding, carbon metabolism, and endoplasmic reticulum protein processing. qRT-PCR revealed that three sHSP genes (PsHSP17.8, PsHSP21, and PsHSP27.4) were upregulated in the response of tree peony to heat stress. Tissue quantification of the transgenic lines (Arabidopsis thaliana) showed that all three genes were most highly expressed in the leaves. The survival rates of transgenic lines (PsHSP17.8, PsHSP21, and PsHSP27.4) restored to normal growth after high-temperature treatment were 43, 36, and 31%, respectively. In addition, the activity of superoxide dismutase, accumulation of free proline, and chlorophyll level was higher than those of the wild-type lines, while the malondialdehyde content and conductivity were lower, and the membrane lipid peroxidation reaction of the wild-type plant was more intense. Our research found several processes and pathways related to heat resistance in tree peony including metabolic process, single-organism process, phenylpropane biosynthesis pathway, and endoplasmic reticulum protein synthesis pathway. PsHSP17.8, PsHSP21, and PsHSP27.4 improved heat tolerance by increasing SOD activity and proline content. These findings can provide genetic resources for understanding the heat-resistance response of tree peony and benefit future germplasm innovation.

Type 2 diabetes (T2D) is a major global public health burden, with β-cell dysfunction a key component in its pathogenesis. However, the exact pathogenesis of β-cell dysfunction in T2D is yet to be fully elucidated. Ferroptosis, a recently discovered regulated form of non-apoptotic cell death, plays a vital role in the development of diabetes and its complications. The current study aimed to identify the key molecules involved in β-cell ferroptosis3 in patients with T2D using the mRNA expression profile data of GSE25724 by bioinformatic approaches. The differentially expressed mRNAs (DE-mRNAs) in human islets of patients with T2D were screened using the islet mRNA expression profiling data from the Gene Expression Omnibus and their intersection with ferroptosis genes was then obtained. Ferroptosis-related DE-mRNA functional and pathway enrichment analysis in T2D islet were performed. Using a protein-protein interaction (PPI) network constructed from the STRING database, Cytoscape software identified ferroptosis-related hub genes in the T2D islet with a Degree algorithm. We constructed a miRNA-hub gene network using the miRWalk database. We generated a rat model of T2D to assess the expression of hub genes. A total of 1,316 DE-mRNAs were identified in the islet of patients between T2D and non-T2D (NT2D), including 221 and 1,095 up- and down-regulated genes. Gene set enrichment analysis revealed that the ferroptosis-related gene set was significantly different in islets between T2D and NT2D at an overall level. A total of 33 ferroptosis-related DE-mRNAs were identified, most of which were significantly enriched in pathways including ferroptosis. The established PPI network with ferroptosis-related DE-mRNAs identified five hub genes (JUN, NFE2L2, ATG5, KRAS, and HSPA5), and the area under the ROC curve of these five hub genes was 0.929 in the Logistic regression model. We constructed a regulatory network of hub genes and miRNAs, and the results showed that suggesting that hsa-miR-6855-5p, hsa-miR-9985, and hsa-miR-584-5p could regulate most hub genes. In rat model of T2D, the protein expression levels of JUN and NFE2L2 in pancreatic tissues were upregulated and downregulated, respectively. These results contribute to further elucidation of ferroptosis-related molecular mechanisms in the pathogenesis of β-cell dysfunction of T2D.

Clusterin (CLU) is an extracellular chaperone involved in reducing amyloid beta (Aβ) toxicity and aggregation. Although previous genome-wide association studies (GWAS) have reported a potential protective effect of CLU on Alzheimer’s disease (AD) patients, how intron-located rs11136000 (CLU) affects AD risk by regulating CLU expression remains unknown. In this study, we integrated multiple omics data to construct the regulated pathway of rs11136000-CLU-AD. In step 1, we investigated the effects of variant rs11136000 on AD risk with different genders and diagnostic methods using GWAS summary statistics for AD from International Genomics of Alzheimer’s Project (IGAP) and UK Biobank. In step 2, we assessed the regulation of rs11136000 on CLU expression in AD brain samples from Mayo clinic and controls from Genotype-Tissue Expression (GTEx). In step 3, we investigated the differential gene/protein expression of CLU in AD and controls from four large cohorts. The results showed that rs11136000 T allele reduced AD risk in either clinically diagnosed or proxy AD patients. By using expression quantitative trait loci (eQTL) analysis, rs11136000 variant downregulated CLU expression in 13 normal brain tissues, but upregulated CLU expression in cerebellum and temporal cortex of AD samples. Importantly, CLU was significantly differentially expressed in temporal cortex, dorsolateral prefrontal cortex and anterior prefrontal cortex of AD patients compared with normal controls. Together, rs11136000 may reduce AD risk by regulating CLU expression, which may provide important information about the biological mechanism of rs9848497 in AD progress.

With the development of automobile intelligence, the security of the Internet of Vehicles has become a key factor that affects the development of intelligent vehicles. However, existing security risk analysis methods for the IoV either focus only on certain levels, such as the component level, or perform only a static analysis. This paper proposes a dynamic attack graph generation method for the IoV to identify and visually display the security risks caused by the associated vulnerabilities in an IoV system. First, using the actual architecture of the IoV, this paper shows how to model the security elements and their relationships in the IoV system and proposes a network security ontology model for this system. Second, it shows how to construct a reasoning rule base according to the causal relationship between the vulnerabilities using the Semantic Web Rule Language Finally, in view of the rapid change in the network topology of the IoV, a dynamic attack graph generation algorithm based on an ontology reasoning engine is proposed, which can effectively reduce the overhead caused by the changes in the attack graph. The effectiveness of the algorithm is demonstrated through an actual security event scenario and a constructed scenario. The experimental results show that the algorithm can dynamically and accurately display the network attack graph of the IoV. The proposed method is helpful in globally analyzing the threat caused by the combined exploitation of the vulnerabilities in an IoV system and risk management.

Background and ObjectiveThere is a paucity of research that has explored “False Alarm” mechanisms. In order to remedy this deficiency in knowledge, the present study used event-related potential (ERP) technology to reveal the mechanisms underlying False Alarm in response to fear stimuli.MethodsThis study selected snakes as experimental materials and the “oddball paradigm” was used to simulate the conditions of False Alarm. The mechanism underlying False Alarm was revealed by comparing cognitive processing similarities and differences between real snakes and toy snakes.ResultsEvent-related potential findings demonstrated that there was no significant difference between N1 and P2 components induced by real and toy snakes in the early processing stage. Compared with toy snakes, real snakes induced smaller N2 amplitude, larger P3 amplitude, and a shorter P3 latency at the late processing stage. The results of brain topographic mapping analysis showed that the brain regions activated by a real or toy snake were basically the same within the time windows of 110–150 and 220–270 ms, respectively. In the time window of 300–360 and 400–500 ms, the degree of brain regions activation with a real snake was significantly greater than that induced by a toy snake.ConclusionFalse Alarm is caused by the brain’s inability to distinguish, in the early stage of cognitive processing, stimulus objects with similar appearances. When the brain is able to distinguish the differences between different stimulus objects in the late stage of cognitive processing, False Alarm disappears.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory damage and cognitive dysfunction. Studies have shown that defective autophagic flux is associated with neuronal dysfunction. Modulating autophagic activity represents a potential method of combating AD. In Chinese medicine, Acori Tatarinowii Rhizoma is used to treat dementia and amnesia. β-Asarone, an active component of this rhizome can protect PC12 cells from Aβ-induced injury and modulate expression of autophagy factors. However, its cytoprotective mechanisms have yet to be discerned. It is unclear whether β-asarone affects autophagic flux and, if it does, whether this effect can alleviate Aβ cell damage. In the present study, we constructed APPswe-overexpressing PC12 cell line as a cell model of Aβ-induced damage and assessed expression of autophagic flux-related proteins as well as the number and morphology of autophagosomes and autolysosomes. Our results show that β-asarone decreases the expression levels of Beclin-1, p62, LC3-Ⅱ, and Aβ1-42. β-Asarone reduced the number of autophagosomes and increased the number of autolysosomes, as determined by confocal laser scanning microscopy and transmission electron microscopy. Our results suggest that β-asarone can protect PC12 cells from Aβ-induced damage by promoting autophagic flux, which may be achieved by enhancing autophagosome-lysosome fusion and/or lysosome function.

Objective: To investigate the outcomes of coronary artery lesions (CALs) and intravenous immunoglobulin (IVIG) resistance in patients with and without neutropenia during the disease course and to explore the relationships between Δ absolute neutrophils count (ΔANC) and the outcomes.Methods: We retrospectively reviewed the medical records of patients hospitalized in Children's Hospital of Soochow University with a main diagnosis of KD during January 2019 and December 2019. 1:4 propensity score matching was carried out to adjust the baseline characteristics. Smoothed plots and threshold effect analyses were performed to reveal the relationships between ΔANC and the outcomes.Results: Of the 438 patients enrolled, 75 (17.1%) were neutropenia cases and 363 (82.9%) were non-neutropenia cases. Patients with neutropenia were younger, had lower levels of initial ANC, white blood cell (WBC) count and C-reactive protein (CRP). Propensity score matching included 75 neutropenia and 247 non-neutropenia patients. No significant difference was found between neutropenia and non-neutropenia groups regarding CALs, coronary artery aneurysms, irregular coronary lumen, IVIG resistance and days of fever duration. There was a non-linear relationship between ΔANC and IVIG resistance. However, threshold effect analysis showed the incidence of IVIG resistance decreased with increasing ΔANC before the turning point (ΔANC = 1.6) (OR = 0.65, 95% CI = 0.50–0.8.4 P = 0.001). On the other hand, there was a linear relationship between ΔANC and CALs, even after adjusting the confounders (OR = 1.06, 95% CI = 1.02–1.11, P = 0.008).Conclusions: Neutropenia after IVIG was not exactly associated with the outcomes. However, ΔANC was in relation to CALs and IVIG resistance.

Kawasaki disease (KD) causes acute systemic vasculitis and has unknown etiology. Since the acute stage of KD is the most relevant, the aim of the present study was to identify hub genes in acute KD by bioinformatics analysis. We also aimed at constructing microRNA (miRNA)–messenger RNA (mRNA) regulatory networks associated with acute KD based on previously identified differentially expressed miRNAs (DE-miRNAs). DE-mRNAs in acute KD patients were screened using the mRNA expression profile data of GSE18606 from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DE-mRNAs were performed with the DAVID database. Target genes of DE-miRNAs were predicted using the miRWalk database and their intersection with DE-mRNAs was obtained. From a protein–protein interaction (PPI) network established by the STRING database, Cytoscape software identified hub genes with the two topological analysis methods maximal clique centrality and Degree algorithm to construct a miRNA-hub gene network. A total of 1,063 DE-mRNAs were identified between acute KD and healthy individuals, 472 upregulated and 591 downregulated. The constructed PPI network with these DE-mRNAs identified 38 hub genes mostly enriched in pathways related to systemic lupus erythematosus, alcoholism, viral carcinogenesis, osteoclast differentiation, adipocytokine signaling pathway and tumor necrosis factor signaling pathway. Target genes were predicted for the up-regulated and down-regulated DE-miRNAs, 10,203, and 5,310, respectively. Subsequently, 355, and 130 overlapping target DE-mRNAs were obtained for upregulated and downregulated DE-miRNAs, respectively. PPI networks with these target DE-mRNAs produced 15 hub genes, six down-regulated and nine upregulated hub genes. Among these, ten genes (ATM, MDC1, CD59, CD177, TRPM2, FCAR, TSPAN14, LILRB2, SIRPA, and STAT3) were identified as hub genes in the PPI network of DE-mRNAs. Finally, we constructed the regulatory network of DE-miRNAs and hub genes, which suggested potential modulation of most hub genes by hsa-miR-4443 and hsa-miR-6510-5p. SP1 was predicted to potentially regulate most of DE-miRNAs. In conclusion, several hub genes are associated with acute KD. An miRNA–mRNA regulatory network potentially relevant for acute KD pathogenesis provides new insights into the underlying molecular mechanisms of acute KD. The latter may contribute to the diagnosis and treatment of acute KD.

Endothelial-to-mesenchymal transition (EndMT) plays an important role in embryonic development and disease progression. Yet, how different members of the transforming growth factor-β (TGF-β) family regulate EndMT is not well understood. In the current study, we report that TGF-β2, but not bone morphogenetic protein (BMP)9, triggers EndMT in murine endothelial MS-1 and 2H11 cells. TGF-β2 strongly upregulates the transcription factor SNAIL, and the depletion of Snail is sufficient to abrogate TGF-β2-triggered mesenchymal-like cell morphology acquisition and EndMT-related molecular changes. Although SLUG is not regulated by TGF-β2, knocking out Slug also partly inhibits TGF-β2-induced EndMT in 2H11 cells. Interestingly, in addition to SNAIL and SLUG, BMP9 stimulates inhibitor of DNA binding (ID) proteins. The suppression of Id1, Id2, or Id3 expression facilitated BMP9 in inducing EndMT and, in contrast, ectopic expression of ID1, ID2, or ID3 abrogated TGF-β2-mediated EndMT. Altogether, our results show that SNAIL is critical and indispensable for TGF-β2-mediated EndMT. Although SLUG is also involved in the EndMT process, it plays less of a crucial role in it. In contrast, ID proteins are essential for maintaining endothelial traits and repressing the function of SNAIL and SLUG during the EndMT process. These data suggest that the control over endothelial vs. mesenchymal cell states is determined, at least in part, by a balance between the expression of SNAIL/SLUG and ID proteins.

Endothelial to mesenchymal transition (EndMT) is a complex biological process that gives rise to cells with multipotent potential. EndMT is essential for the formation of the cardiovascular system during embryonic development. Emerging results link EndMT to the postnatal onset and progression of fibrotic diseases and cancer. Moreover, recent reports have emphasized the potential for EndMT in tissue engineering and regenerative applications by regulating the differentiation status of cells. Transforming growth factor β (TGF-β) engages in many important physiological processes and is a potent inducer of EndMT. In this review, we first summarize the mechanisms of the TGF-β signaling pathway as it relates to EndMT. Thereafter, we discuss the pivotal role of TGF-β-induced EndMT in the development of cardiovascular diseases, fibrosis, and cancer, as well as the potential application of TGF-β-induced EndMT in tissue engineering.

Left atrial (LA) fibrosis is a major arrhythmogenic substrate for atrial fibrillation (AF). The purpose of this study was to assess whether isoproterenol (ISO) induces LA fibrosis and increases susceptibility to AF, exploring the underlying mechanisms. Male Sprague-Dawley rats were subcutaneously injected ISO once per day for 2 days. Five weeks after injection, the ISO group had higher susceptibility AF and prolonged AF duration compared with the control group. ISO decreased LA conduction velocity (CV) and increased LA conduction heterogeneity. ISO increased fibrosise areas and the protein levels of collagen types I and III in the left atrium. Antifibrosis drug pirfenidone decreased AF occurrence and reduced LA fibrosis in ISO treated rats. ISO injection induced atrial ischemia infarction by increasing heart rate and decreasing diastolic and systolic blood pressures. These findings demonstrated that ISO increases susceptibility to AF by increasing LA fibrosis and LA conduction abnormalities 5 weeks after injection. ISO injection induces atrial ischemic injury is the main cause of fibrosis. Rats with ISO-induced LA fibrosis may be used in further AF research.

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10-20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS. [ABSTRACT FROM AUTHOR]

Objective: Arteriolosclerosis cerebral small vessel disease (CSVD) is a common type of CSVD. This study aimed to explore the factors associated with cognitive function and total MRI burden related to the disease. Methods: The demographic characteristics, clinical manifestations, cognitive function score, Barthel Index (BI), blood test index, and follow-up results of arteriolosclerosis CSVD patients treated for the first time in our hospital from January 2014 to August 2022 were collected. White matter hyperintensity (WMH) Fazekas score, total MRI burden, and cerebral atrophy grade were evaluated according to brain MRI findings. Factors associated with CSVD cognitive function were analyzed by binary logistic regression. The correlative factors related to the total MRI burden of CSVD were analyzed by ordered multiple logistic regression. Results: A total of 146 patients were included in this study, of which 132 cases (90.4%) had hypertension. There were 108 patients (74.0%) with cognitive dysfunction, 97 patients (66.4%) with balance and gait disorders, and 83 patients (56.8%) with moderate-to-severe dependence in daily life (BI ≤ 60 points). Of 146 patients, 79 (54.1%) completed clinical and imaging follow-ups for a median of 3 years. The number of patients with cognitive impairment and BI ≤ 60 points after follow-up significantly increased compared with the first admission (P < 0.001). There were also significant differences in total MRI burden (P = 0.001), WMH Fazekas score, and cerebral atrophy grade (P < 0.001). Mean age (P = 0.012), median deep WMH Fazekas score (P = 0.028), and median deep (P < 0.001) and superficial (P =0.002) cerebral atrophy grade of patients with cognitive impairment at first admission were all higher than those with non-cognitive impairment. Multivariate analysis showed that deep cerebral atrophy was independently and significantly associated with cognitive impairment of CSVD (P = 0.024), and hypertension was significantly and independently associated with total MRI burden (P = 0.001). Conclusion: The disease course of arteriolosclerosis CSVD may be related to cognitive function and total MRI burden. Deep cerebral atrophy was an independent risk factor for cognitive dysfunction in arteriolosclerosis CSVD, and hypertension was an independent risk factor for total MRI burden. [ABSTRACT FROM AUTHOR]

Background and purposeThe development of intracerebral hemorrhage (ICH) is closely related to mechanical forces. However, noninvasively evaluating mechanical forces for ICH patients in the current clinical setting is challenging. In this study, we aimed to build an easily accessible stiffness index (STI) and evaluate the stiffness of the perihematomal edema (PHE) region in ICH patients.Materials and methodsIn this retrospective study, two cohorts of 57 patients were included. One cohort (the exploratory cohort) comprised patients with both standard b-value diffusion-weighted imaging (sDWI) (b-values of 0 and 1,000 s/mm2, b0 and b1000) and higher b-value diffusion-weighted imaging (hDWI) (b-values of 200 and 1,500 s/mm2). Another cohort (the hemorrhage cohort) consisted of patients who were diagnosed with ICH and who underwent sDWI within 48 h from onset. The hDWI-based virtual shear modulus (μdiff) was calculated and correlated with the sDWI data in the exploratory cohort. In the hemorrhage cohort, STI maps that were used to estimate μdiff were generated. The mean STI (mSTI) and coefficient of variation (COV) of the STI were computed on the basis of the STI maps in the whole and largest-slice PHE regions.ResultsThe STI could be calculated with the Equation 0.047697*S1000-0.022944*S0 + 5.359883, where S1000 and S0 represent the signal intensities of the b1000 and b0 images, respectively. In the whole and largest-slice PHE regions, both the mSTI and COV were correlated with the hematoma volume (p

Background: Chimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity. Methods: This study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, creactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers. Results: We found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion. Conclusions: Our results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Depression and type 2 diabetes (T2D) are serious public health problems with irreversible health consequences and a significant economic burden on the healthcare system. Previous studies have suggested that blood urea nitrogen (BUN) was inversely longitudinally associated with incidence of diabetes and depression in adults, but few well-designed studies have examined the effects of status of T2D on the full range of relationship between BUN and depression. Methods: The analysis sample consisted of adults aged≥20 years from the 2007-2014 National Health and Nutrition Examination Survey (NHANES) who completed the Patient Health Questionnaire-9 (PHQ-9), involving 19,005 participants. By stratifying participants according to T2D status, we further assessed the difference between BUN and risk of depression in participants with and without T2D using multivariate logistic regression (interaction test). Results: In this cross-sectional study, the association between BUN and depression prevalence appeared to differ between the T2D and non-T2D groups (OR: 1.00, 95% Cl: 0.95-1.05 vs. OR: 0.89, 95% Cl: 0.85-0.93). In addition, there was evidence of an interaction between BUN levels and T2D status in reducing the risk of depression (P value for interaction = 0.032.) The relationship between BUN and depressive symptoms was significant in nonT2D subjects (P < 0.001), but not in T2D (P = 0.940). Conclusions: Our findings suggest that there is a significant relationship between BUN and depression, and T2D status may influence the association between BUN and the risk of depression. Such findings require further prospective studies to provide more evidence. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) was previously known as chronic bronchitis and emphysema. It has various main symptoms, such as dyspnea, chronic cough, and sputum, and is often accompanied by dysphagia. Although many published clinical reports have described COPD-related dysphagia, the physiological mechanisms underlying swallowing changes due to COPD remain unclear. Therefore, we analyzed how COPD affects the swallowing reflex using COPD model rats. We performed an electrophysiological study of respiration and swallowing using COPD model induced by intratracheal administration of porcine pancreatic elastase and lipopolysaccharide in Sprague-Dawley male rats. To identify the respiration and swallowing responses, electromyographic activity was recorded from the diaphragm, digastric (Dig), and thyrohyoid (TH) muscles. We confirmed COPD using micro-computed tomography analysis and hematoxylin and eosin staining of the lungs. The duty cycle was defined as the ratio of the inspiration duration to the total respiratory duration. In COPD model rats, the duty cycle was significantly higher than that in control rats. The frequency of the swallowing reflex evoked by electrical stimulation of the superior laryngeal nerve during the inspiration phase was higher in COPD model rats than in control rats. Furthermore, long-term COPD altered Dig and TH muscle activity without pathological muscle change. Our results suggest that COPD increases the frequency of swallowing initiation during the inspiration phase. Furthermore, long-term COPD affects swallowing-related muscle activity without pathological muscle changes. These physiological changes may increase the risk of developing dysphagia. Further studies are necessary to clarify the mechanisms contributing to the functional changes in respiration and swallowing in COPD.

BackgroundMeningioma is a common non-glial tumor of the brain. Extracranial meningiomas in the parapharyngeal space are especially rare. Herein we report a case of extracranial meningioma in the parapharyngeal space and give a comprehensive description of its complete clinical course and radiological findings, which may provide helpful information in the diagnosis and treatment of extracranial meningiomas in the parapharyngeal space.Case PresentationA 61-year-old man presented a slowly increased mass under the left ear without pain and numbness over one year. Ultrasound examination detected a hypoechoic uneven mass behind the left parotid gland with a clear boundary, and color Doppler flow imaging revealed blood flow signals within the mass. Unenhanced computed tomography (CT) of the craniofacial region revealed a homogenous soft tissue mass in the parapharyngeal space without calcification. Magnetic resonance imaging (MRI) showed that a homogenous soft tissue mass was hyperintense on T2-weighted image, hypointense on T1-weighted image, and obviously enhanced after contrast enhancement in the parapharyngeal space. Coronal MRI showed that the lesion originated from basicranial dura extending into parapharyngeal space through the left foramen ovale at the skull base. Finally, histopathological and immunohistochemical analyses confirmed the final diagnosis of extracranial meningiomas in the parapharyngeal space.ConclusionExtracranial meningiomas of the parapharyngeal space are rare and often pose a diagnostic challenge. Preoperative imaging examinations, especially CT and MRI, can aid in the accurate preoperative diagnosis, especially when intracranial extensions and dural tail signs are observed.

ObjectiveThe aim of this study is to compare the efficacy and safety of complete multi-level vs. iliac-only revascularization for the treatment of concomitant iliac and superficial femoral artery (SFA) occlusive disease.MethodsA total of 139 consecutive adult patients with severe stenosis and occlusive iliac and SFA disease with Rutherford categories 2–5 underwent multi-level (n = 71) and iliac-only (n = 68) revascularization at the Department of Intervention Vascular Surgery, Peking University Third Hospital, and Aerospace Center Hospital, between March 2015 and June 2017. Improvement in Rutherford class, perioperative major adverse events, the length of stay, survival rate, and limb salvage rate were assessed. The neutrophil–lymphocyte ratio and platelet–lymphocyte ratio were compared between the two groups.ResultsAt 48 months, improvement in the Rutherford category was observed in the two groups with no significant difference (P = 0.809). Additionally, the two groups were similar concerning the primary patency (84.0% vs. 79.1%, P = 0.717) and limb salvage rate (93.1% vs. 91.3%, P = 0.781). A higher proportion of the perioperative major adverse events (33.8% vs. 27.9%, P = 0.455), the all-cause mortality (11.3% vs. 8.8%, P = 0.632), and the average length of hospital stay [7.0 (6.0, 11.0) vs. 7.0 (5.0, 8.0), P = 0.037] were seen in the multi-level group compared with the iliac-only group.ConclusionFor concomitant iliac and superficial femoral artery occlusive disease, iliac-only revascularization has favorable efficacy and safety outcomes compared with complete multi-level revascularization in selected patients with patent profunda femoris artery and at least one healthy outflow tract of the infrapopliteal artery.

BackgroundThymic cysts are often misinterpreted as thymomas or lymph nodes, then leading to unnecessary thymectomy. The purpose of this study was to investigate how the adjacent large vessels artifactually affected attenuation values of thymic cysts on contrast–enhanced CT (CE-CT).MethodsIn this retrospective study, a total of 84 patients were included with pathological diagnosis of thymic cysts and preoperative CE-CT. Quantitative measurements of the size, CT attenuation of thymic cysts and CT attenuation of adjacent large vessels were performed on preoperative CE-CT. According to the absolute change in attenuation of the cysts between contrast-enhanced and nonenhanced CT, the patients were classified into the groups of artifactual hyper-density, unchanged density, and artifactual hypo-density. CT characteristics were compared between the three groups. Furthermore, multivariable logistic regression analysis was performed to determine the independent factors for artifactual hyper-density.ResultsThe group of artifactual hyper-density had smaller short diameter of the cysts, higher postcontrast attenuation values and lower nonenhanced attenuation values of the adjacent large vessel. Furthermore, the multivariable logistic analysis showed that artifactual hyper-density of thymic cysts was negatively associated with nonenhanced attenuation of adjacent large vessel, and positively associated with postcontrast attenuation of adjacent large vessel and postcontrast attenuation of cysts.ConclusionsMost cases with >20 HU nonenhanced CT attenuation in surgically resected cases. Artifactual hyper-density─pseudo-enhancement phenomenon of thymic cysts was more apparent in higher increasing attenuation of adjacent large vessels on CE-CT. A well understanding of this phenomenon can help reduce preoperative misdiagnosis and unnecessary thymectomy.

BackgroundColchicine is a traditional medication that is currently approved to treat gout and familial Mediterranean fever (FMF). However, colchicine has a wide range of anti-inflammatory activities, and several studies have indicated that it may be useful in a variety of other conditions, such as rheumatic disease, cardiac disease, and cancer. Osteosarcoma, the most common type of bone sarcoma, is derived from primitive bone-forming mesenchymal cells. In this study, we investigated whether colchicine could be used to treat osteosarcoma through the regulation of cell cycle signaling.MethodsTwo human osteosarcoma cell lines, U2OS and Saos-2, were used. A clonogenic assay was used to determine the antiproliferative effects of colchicine on osteosarcoma cells. Reactive oxygen species (ROS) production and apoptosis were measured by flow cytometry. Migration and invasion assays were performed to investigate the inhibitory effects of colchicine. The signaling pathways related to colchicine treatment were verified by GO biological process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.ResultsColchicine was selected as the lead compound based on the results of initial screening and cell viability assays conducted in Saos-2 and U2Os cells. Colchicine reduced the viability of Saos-2 and U2OS cells in a concentration-dependent manner. It also significantly inhibited colony-forming ability and induced ROS production and apoptosis. It also inhibited the migration and invasion of both Saos-2 and U2OS cells. GOBP and KEGG enrichment analyses indicated the involvement of microtubule-based processes and cancer-related pathways.ConclusionsThese findings suggest that colchicine has therapeutic potential in osteosarcoma.

This study aimed to investigate the effects of physical therapists’ exercise instructions in Japanese patients with type 2 diabetes. Thirty-six participants were recruited from the outpatient clinic at Matsushita Memorial Hospital, Osaka, Japan from June 2020 to September 2020 and were randomly assigned to either the non-intervention or intervention group. The intervention group received exercise instructions from physical therapists for 30 min at baseline (week 0) and at week 4 by referring to ambulatory accelerometer records. Laboratory parameters, physical activity, body composition, motor skill, and transtheoretical model were assessed in both the groups at baseline (week 0) and week 8. In week 8, patients in the intervention group had a statistically significant reduction in HbA1c levels compared with those in the non-intervention group (7.3% [6.8-%–7.9%] vs. 7.4% [7.3%–7.7%], P = 0.04). The number of steps per day (P = 0.001), energy expenditure (P = 0.01), lower extremity muscle strength (P = 0.002), and 6-min walk test results (P = 0.04) were significantly increased in the intervention group compared with those in the non-intervention group in week 8. The transtheoretical model varied between baseline (week 0) and week 8 only in the intervention group (P < 0.001). Thus, outpatient exercise instructions from physical therapists could improve glycemic control owing to physical activity by improving motor skills and changing the transtheoretical model in Japanese patients with type 2 diabetes.

Vitamin E is an essential fat-soluble nutrient mainly found in vegetable oils, nuts, and other foods. In this study, we evaluated the contribution of commonly consumed foods to the vitamin E dietary intake of the population in relation to their consumption practices. In addition, the vitamin E intakes of Chinese residents were compared in different regions of China and in different years. The results showed that vegetable oil was the main source of vitamin E dietary intake for Chinese residents, accounting for 46.76% of total dietary intake of vitamin E, followed by cereals, vegetables, meat, aquatic products, eggs, legumes, nuts, fruits and dairy products. Among all vegetable oils, rapeseed oil was the highest contributor of vitamin E, accounting for 10.73% of all foods. Due to dietary habits and regional differences, vitamin E intake also varies greatly among residents in different regions of China and has increased yearly from 1982 to 2020. This study provides with scientific evidence for reasonable VE supplementation.

It still remains unclear how the suprahyoid muscles function in bolus formation during mastication. This study aimed to investigate the contributory role of the suprahyoid muscles during mastication. A total of 20 healthy young volunteers were asked to perform tongue pressure generation tasks and unilateral mastication tasks using peanuts and two different types of rice crackers. Surface electromyographic (EMG) activity of the masseter and suprahyoid muscles and mandibular kinematics were recorded. Suprahyoid activity increased with increasing tongue pressure. Masticatory duration until the first deglutition differed significantly among the different foods; the harder the food, the longer the duration. This was also the case in masseter activity per masticatory cycle. Masticatory rate and suprahyoid activity per masticatory cycle were significantly higher during soft rice cracker mastication. Masseter activity was higher on the masticatory side than on the non-masticatory side, however, there was no difference in suprahyoid activity between the sides. Suprahyoid activity and jaw gape showed significant positive correlation in the early stage on both the masticatory and non-masticatory sides. The suprahyoid muscles functioned dominantly for jaw-opening during peanut mastication, and for bolus formation, especially in the late stage during soft rice cracker mastication. Bolus formation was performed dominantly on the masticatory side during rice cracker mastication. These findings clearly demonstrate a functional role of the suprahyoid muscles during mastication of solid foods from assessments using both EMG activity and mandibular kinematic recordings.

Examining the coordination of respiration and swallowing is important for elucidating the mechanisms underlying these functions and assessing how respiration is linked to swallowing impairment in dysphagic patients. In this study, we assessed the coordination of respiration and swallowing to clarify how voluntary swallowing is coordinated with respiration and how mastication modulates the coordination of respiration and swallowing in healthy humans. Twenty-one healthy volunteers participated in three experiments. The participants were asked to swallow 3 ml of water with or without a cue, to drink 100 ml of water using a cup without breathing between swallows, and to eat a 4-g portion of corned beef. The major coordination pattern of respiration and swallowing was expiration–swallow–expiration (EE type) while swallowing 3 ml of water either with or without a cue, swallowing 100 ml of water, and chewing. Although cueing did not affect swallowing movements, the expiratory time was lengthened with the cue. During 100-ml water swallowing, the respiratory cycle time and expiratory time immediately before swallowing were significantly shorter compared with during and after swallowing, whereas the inspiratory time did not differ throughout the recording period. During chewing, the respiratory cycle time was decreased in a time-dependent manner, probably because of metabolic demand. The coordination of the two functions is maintained not only in voluntary swallowing but also in involuntary swallowing during chewing. Understanding the mechanisms underlying respiration and swallowing is important for evaluating how coordination affects physiological swallowing in dysphagic patients.

Background and Objective: An increasing number of epidemiological original studies suggested that long-term exposure to particulate matter (PM2.5 and PM10) could be associated with the risk of myocardial infarction (MI), but the results were inconsistent. We aimed to synthesized available cohort studies to identify the association between ambient air pollution (PM2.5 and PM10) and MI risk by a meta-analysis.Methods: PubMed and Embase were searched through September 2019 to identify studies that met predetermined inclusion criteria. Reference lists from retrieved articles were also reviewed. A random-effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI).Results: Twenty-seven cohort studies involving 6,764,987 participants and 94,540 patients with MI were included in this systematic review. The pooled results showed that higher levels of ambient air pollution (PM2.5 and PM10) exposure were significantly associated with the risk of MI. The pooled relative risk (RR) for each 10-μg/m3 increment in PM2.5 and PM10 were 1.18 (95% CI: 1.11–1.26), and 1.03 (95% CI: 1.00–1.05), respectively. Exclusion of any single study did not materially alter the combined risk estimate.Conclusions: Integrated evidence from cohort studies supports the hypothesis that long-term exposure to PM2.5 and PM10 is a risk factor for MI.

The cornea is the main refractive medium of the human eye, and its clarity is critical to visual acuity. Corneal optical density (COD) is an important index to describe corneal transparency. Intact corneal epithelial and endothelial cells, regular arrangement of collagen fibers in the stroma, and normal substance metabolism are all integral for the cornea to maintain its transparency. In the last two decades, the Pentacam Scheimpflug imaging system has emerged as a breakthrough for the measurement of COD (also called corneal densitometry). It has been found that a wide variety of factors such as age, refractive status, and corneal diseases can affect COD. Different corneal refractive surgery methods also change COD in different corneal regions and layers and affect visual acuity following the surgery. Thus, COD has gradually become a significant indicator to evaluate corneal health, one on which the attention of clinicians has been increasingly focused.