Forkhead box M1 mediates metabolic reprogramming in human colorectal cancer cells.

Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assays, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mTOR signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.

Inflammatory activity evaluation in patients with axial spondyloarthritis using MRI relaxometry and mucosal-associated invariant T cells.

Background: Currently, there is a lack of an objective quantitative measure to comprehensively evaluate the inflammatory activity of axSpA, which poses certain challenges in accurately assessing the disease activity. Objective: To explore the value of combined-parameter models of sacroiliac joints (SIJs) MRI relaxometry and peripheral blood Mucosal-associated invariant T (MAIT) cells in evaluating the inflammatory activity of axial spondyloarthritis (axSpA). Methods: This retrospective clinical study included 88 axSpA patients (median age 31.0 (22.0, 41.8) years, 21.6% females) and 20 controls (median age 28.0 (20.5, 49.5) years, 40.0% females). The axSpA group was classified into active subgroup (n=50) and inactive subgroup (n=38) based on ASDAS-CRP. All participants underwent SIJs MRI examination including T1 and T2* mapping, and peripheral blood flow cytometry analysis of MAIT cells (defined as CD3+Vα7.2+CD161+) and their activation markers (CD69). The T1 and T2* values, as were the percentages of MAIT cells and CD69+MAIT cells were compared between different groups. Combined-parameter models were established using logistic regression, and ROC curves were employed to evaluate the diagnostic efficacy. Results: The T1 values of SIJs and %CD69+MAIT cells in the axSpA group and its subgroup were higher than the control group (p<0.05), while %MAIT cells were lower than the control group (p<0.05). The T1 values and %CD69+MAIT cells correlated positively, while %MAIT cells correlated negatively, with the ASDAS-CRP (r=0.555, 0.524, -0.357, p<0.001). Between the control and axSpA groups, and between the inactive and active subgroups, the combined-parameter model T1 mapping+%CD69+MAIT cells has the best efficacy (AUC=0.959, 0.879, sensibility=88.6, 70%, specificity=95.0, 94.7%, respectively). Conclusion: The combined-parameter model T1 mapping+%CD69+MAIT cells allows a more accurate evaluation of the level of inflammatory activity.

Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions.

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.

Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

PURPOSE: Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. METHODS: The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. RESULTS: Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1ß in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. CONCLUSION: Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Multi-omics reveals the molecular mechanism of the combined toxic effects of PFOA and 4-HBP exposure in MCF-7 cells and the key player: mTORC1.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Performance of T2 mapping in the staging of Graves' ophthalmopathy based on different region of interest selection methods.

BACKGROUND: Discriminating the stage of Graves' ophthalmopathy (GO) is crucial for clinical decision. Application of conventional T2-weighted imaging in the staging is still limited. PURPOSE: To evaluate the performance of T2 mapping based on two different regions of interest (ROIs) for staging GO. MATERIAL AND METHODS: In total, 56 GO patients were retrospectively enrolled and divided into two groups according to the clinical activity score (CAS). T2 relaxation time (T2RT) of extraocular muscle (EOM) on T2 mapping based on two different ROIs (T2RTROI-1: ROIs were drawn separately in the four EOMs; T2RTROI-2: ROI was drawn in the most inflamed EOM) was measured and compared between active and inactive groups. RESULTS: Both T2RTROI-1 and T2RTROI-2 values in the active GO were significantly higher than those of inactive GO (P <0.001). T2RTROI-1 and T2RTROI-2 values were positively correlated with CAS (rs=0.73, 0.69; P <0.001). When the T2RTROI-1 value of 83.3 ms and T2RTROI-2 value of 106.3 ms were used as cutoff values for staging GO, respectively, the best results were obtained with areas under the curve (AUCs) of 0.822 and 0.827. There was no significant difference for AUCs between T2RTROI-1 and T2RTROI-2 (P = 0.751). Excellent and good inter-observer agreements were achieved in quantitative measurements for T2RTROI-1 and T2RTROI-2 values, respectively, with intraclass correlation coefficients of 0.954 and 0.882. CONCLUSION: The T2RT values derived from two different ROIs were useful for assessment of disease activity. Taking reproducibility and diagnostic performance into consideration, T2RTROI-1 would be an ideal image biomarker for staging GO compared to T2RTROI-2.

Depression in Polycystic Ovary Syndrome: Focusing on Pathogenesis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies. Appeared originally in Front Psychiatry 2022; 13:1001484.

A structured iterative division approach for non-sparse regression models and applications in biological data analysis.

In this paper, we focus on the modeling problem of estimating data with non-sparse structures, specifically focusing on biological data that exhibit a high degree of relevant features. Various fields, such as biology and finance, face the challenge of non-sparse estimation. We address the problems using the proposed method, called structured iterative division. Structured iterative division effectively divides data into non-sparse and sparse structures and eliminates numerous irrelevant variables, significantly reducing the error while maintaining computational efficiency. Numerical and theoretical results demonstrate the competitive advantage of the proposed method on a wide range of problems, and the proposed method exhibits excellent statistical performance in numerical comparisons with several existing methods. We apply the proposed algorithm to two biology problems, gene microarray datasets, and chimeric protein datasets, to the prognostic risk of distant metastasis in breast cancer and Alzheimer's disease, respectively. Structured iterative division provides insights into gene identification and selection, and we also provide meaningful results in anticipating cancer risk and identifying key factors.

Best acupuncture method for mammary gland hyperplasia: Evaluation of randomized controlled trials and Bayesian network meta-analysis.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis.

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.

UPLC-MS based metabonomics revealed the protective effects of Buyang Huanwu decoction on ischemic stroke rats.

Objective: Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy. Methods: We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Results: Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels. Conclusions: This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.

Dual intervention on the gut and skin microbiota attenuates facial cutaneous aging.

The gut and skin microbiota are microbial barriers, resisting harmful foreign microorganisms and maintaining internal homeostasis. Dysbiosis of the gut and skin microbiota is involved in aging progression. However, interventions targeting facial skin wellness taking into account the gut-skin axis are scarce. In this study, the impact of an eight-week intervention with oral (O), topical (T), and both oral and topical (OT) xylo-oligosaccharides (XOS) by regulating gut and skin microbiota on facial cutaneous aging was investigated in a double-blind placebo-controlled trial in females. An increase in the proportion of participants with skin rejuvenation was observed, along with a significant reduction in facial pores after OT intervention. The reduction of cutaneous Cutibacterium by OT intervention was greater than that in the O and T groups. These interventions can change the skin microbial structure. Intestinal Bifidobacterium was enriched only by dual treatment with oral and topical XOS. Function prediction analysis revealed a decrease in K02770 encoding fructose-1-phosphate kinase involved in de novo lipid synthesis from fructose with dual intervention, suggesting that inhibition of lipophilic Cutibacterium may contribute to reducing facial pores. Overall, the dual XOS intervention approach is most effective for improving both gut and skin microbiota, as well as facial skin aging.

Relationships between rumination and different types of rapid eye movement sleep in patients with chronic insomnia disorder.

BACKGROUND AND OBJECTIVE: Rumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. METHODS: This study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. RESULTS: The CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher ß power during REM sleep, higher ß and σ power during phasic REM sleep, and higher ß, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with ß power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. CONCLUSION: The CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (ß) wave power in REM sleep.

Changed nocturnal levels of stress-related hormones couple with sleep-wake states in the patients with chronic insomnia disorder: A clinical pilot study.

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.

Synthesis and Selective Anticancer Activity Evaluation of 2-phenylacrylonitrile Derivatives as Tubulin Inhibitors.

OBJECTIVE: This study aimed at synthesizing 13 series of novel derivatives with 2-phenylacrylonitrile, evaluating antitumor activity both in vivo and in vitro, and obtaining novel tubulin inhibitors. METHOD: The 13 series of 2-phenylacrylonitrile derivatives were synthesized by Knoevenagel condensation and the anti-proliferative activities were determined by MTT assay. The cell cycle and apoptosis were analyzed by flow cytometer. Quantitative cell migration was performed using 24-well Boyden chambers. The proteins were detected by western blotting. in vitro kinetics of microtubule assembly was measured using ELISA kit for Human ß-tubulin (TUBB). Molecular docking was done by Discovery Studio (DS) 2017 Client online tool. RESULTS: Among the derivatives, compound 1g2a possessed strong inhibitory activity against HCT116 (IC50 = 5.9 nM) and BEL-7402 (IC50 = 7.8 nM) cells. Compound 1g2a exhibited better selective antiproliferative activities and specificities than all the positive control drugs, including taxol. Compound 1g2a inhibited proliferation of HCT116 and BEL-7402 cells by arresting them in the G2/M phase of the cell cycle, inhibited the migration of HCT116 and BEL-7402 cells and the formation of cell colonies. Compound 1g2a showed excellent tubulin polymerization inhibitory activity on HCT116 and BEL-7402 cells. The results of molecular docking analyses showed that 1g2a may inhibit tubulin to exert anticancer effects. CONCLUSION: Compound 1g2a shows outstanding antitumor activity both in vivo and in vitro and has the potential to be further developed into a highly effective antitumor agent with little toxicity to normal tissues.

Levels, Toxic Effects, and Risk Assessment of Pyrrolizidine Alkaloids in Foods: A Review.

Pyrrolizidine alkaloids (PAs) are naturally occurring secondary metabolites of plants. To date, more than 660 types of PAs have been identified from an estimated 6000 plants, and approximately 120 of these PAs are hepatotoxic. As a result of PAs being found in spices, herbal teas, honey, and milk, PAs are considered contaminants in foods, posing a potential risk to human health. Here, we summarize the chemical structure, toxic effects, levels, and regulation of PAs in different countries to provide a better understanding of their toxicity and risk assessment. With recent research on the risk assessment of PAs, this review also discusses the challenges facing this field, aiming to provide a scientific basis for PA toxicity research and safety assessment.

The value of coordinated analysis of multimodal atherosclerotic plaque imaging in the assessment of cardiovascular and cerebrovascular events.

Background: Although atherosclerosis (AS) can affect multiple vascular beds, previous studies have focused on the analysis of single-site AS plaques. Objective: The aim of this study is to explore the differences or similarities in the characteristics of atherosclerotic plaque found in the internal carotid artery, cerebral artery, and coronary artery between patients with atherosclerotic cardiovascular disease (ASCVD) and those without events. Methods: Patients aged ≥ 18 years who underwent both high-resolution vessel wall imaging (HR-VWI) and coronary computed tomography angiography (CCTA) were retrospectively collected and categorized into the ASCVD group and the non-event group. The plaques were then categorized into culprit plaques, non-culprit plaques, and non-event plaques. Plaque morphological data such as stenosis, stenosis grades, plaque length (PL), plaque volume (PV), minimal lumen area (MLA), enhancement grade, and plaque composition data such as calcified plaque volume (CPV), fibrotic plaque volume (FPV), fibro-lipid plaque volume (FLPV), lipid plaque volume (LPV), calcified plaque volume ratio (CPR), fibrotic plaque volume ratio (FPR), fibro-lipid plaque ratio (FLPR), lipid plaque volume ratio (LPR), intraplaque hemorrhage volume (IPHV), and intraplaque hemorrhage volume ratio (IPHR)were recorded and analyzed. Results: A total of 44 patients (mean age 66 years, SD 9 years, 28 men) were included. In cervicocephalic plaques, the ASCVD group had more severe stenosis grades (p = 0.030) and demonstrated significant differences in LPV, LPR, and CPV (p = 0.044, 0.030, 0.020) compared with the non-event group. In coronary plaques, the ASCVD group had plaques with greater stenosis (p < 0.001), more severe stenosis grades (p < 0.001), larger volumes (p = 0.001), longer length (p = 0.008), larger FLPV (p = 0.012), larger FPV (p = 0.002), and higher FPR (p = 0.043) compared with the non-event group. There were significant differences observed in stenosis (HR-VWI, CCTA: p < 0.001, p < 0.001), stenosis grades (HR-VWI, CCTA: p < 0.001, p < 0.001), plaque length (HR-VWI, CCTA: p = 0.028, p < 0.001), and plaque volume (HR-VWI, CCTA: p = 0.013, p = 0.018) between the non-event plaque, non-culprit plaque, and culprit plaque. In the image analysis of HR-VWI, there were differences observed between IPHR (p < 0.001), LPR (p = 0.001), FPV (p = 0.011), and CPV (p = 0.015) among the three groups of plaques. FLPV and FPV were significantly different among the three different plaque types from the coronary artery (p = 0.043, p = 0.022). Conclusion: There is a consistent pattern of change in plaque characteristics between the cervicocephalic and coronary arteries in the same patient.

Beyond diagnosis: Leveraging routine blood and urine biomarkers to predict severity and functional outcome in acute ischemic stroke.

Background: The initial severity of acute ischemic stroke (AIS) is a crucial predictor of the disease outcome. In this study, blood and urine biomarkers from patients with AIS were measured to estimate stroke severity and predict long-term stroke outcomes. Methods: The medical records of patients with AIS between October 2016 and May 2020 were retrospectively analyzed. The relationships of blood and urine biomarkers with stroke severity at admission were evaluated in patients with AIS. Predictive models for initial stroke severity and long-term prognosis were then developed using a panel of identified biomarkers. Results: A total of 2229 patients were enrolled. Univariate analysis revealed 12 biomarkers associated with the National Institutes of Health Stroke Scale scores at admission. The area under the curve values for predicting initial stroke severity and long-term prognosis on the basis of these biomarkers were 0.7465, 0.7470, and 0.8061, respectively. Among multiple tested machine-learning, eXtreme gradient boosting exhibited the highest effectiveness in predicting 90-day modified Rankin Scale scores. SHapley Additive exPlanations revealed fasting glucose, albumin, hemoglobin, prothrombin time, and urine-specific gravity to be the top five most crucial biomarkers. Conclusion: These findings demonstrate that clinically available blood and urine biomarkers can effectively estimate initial stroke severity and predict long-term prognosis in patients with AIS. Our results provide a scientific basis for developing tailored clinical treatment and management strategies for AIS, through incorporating liquid biomarkers into stroke risk assessment and patient care protocols for patients with AIS.

Patients with first-episode psychosis in northern Taiwan: neurocognitive performance and niacin response profile in comparison with schizophrenia patients of different familial loadings and relationship with clinical features.

BACKGROUND: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. METHODS: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients' impairment on the CPT, WCST, and NRA. RESULTS: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: -1.24 for NRA, - 1.06 for undegraded d', - 0.70 for degraded d', - 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. CONCLUSIONS: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation.

In Vivo Imaging of γ-Glutamyl Transferase in Cardiovascular Diseases with a Photoacoustic Probe.

In this work, a photoacoustic (PA) probe, HDS-GGT, was developed for the in vivo imaging of cardiovascular diseases by monitoring the γ-glutamyl transferase (GGT) dynamics. HDS-GGT exhibited a stable PA signal with auxiliary absorbance and NIRF variation after the trigger by GGT. In all three modalities of absorbance, NIRF, and PA, HDS-GGT could quantitatively reflect the GGT level. In PA modality, HDS-GGT indicated the practical advantages including high sensitivity, high stability, and high specificity. In living oxidized low-density lipoprotein-induced RAW264.7 cells, HDS-GGT indicated proper capability for imaging the plaques by visualizing the GGT dynamics. Moreover, during imaging in living model mice, HDS-GGT was achieved to distinguish the plaques from healthy blood vessels via a multiview PA presentation. HDS-GGT could also suggest the severity of plaques in the extracted aorta from the model mice, which was consistent with the histological staining results. The information herein might be useful for future investigations on cardiovascular diseases.