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1.
Nat Immunol ; 25(7): 1296-1305, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38806708

ABSTRACT

Inflammatory pain results from the heightened sensitivity and reduced threshold of nociceptor sensory neurons due to exposure to inflammatory mediators. However, the cellular and transcriptional diversity of immune cell and sensory neuron types makes it challenging to decipher the immune mechanisms underlying pain. Here we used single-cell transcriptomics to determine the immune gene signatures associated with pain development in three skin inflammatory pain models in mice: zymosan injection, skin incision and ultraviolet burn. We found that macrophage and neutrophil recruitment closely mirrored the kinetics of pain development and identified cell-type-specific transcriptional programs associated with pain and its resolution. Using a comprehensive list of potential interactions mediated by receptors, ligands, ion channels and metabolites to generate injury-specific neuroimmune interactomes, we also uncovered that thrombospondin-1 upregulated by immune cells upon injury inhibited nociceptor sensitization. This study lays the groundwork for identifying the neuroimmune axes that modulate pain in diverse disease contexts.


Subject(s)
Nociceptors , Pain , Animals , Mice , Pain/immunology , Pain/metabolism , Nociceptors/metabolism , Transcriptome , Mice, Inbred C57BL , Inflammation/immunology , Male , Macrophages/immunology , Macrophages/metabolism , Disease Models, Animal , Thrombospondin 1/metabolism , Thrombospondin 1/genetics , Skin/immunology , Skin/metabolism , Skin/pathology , Zymosan , Single-Cell Analysis , Neuroimmunomodulation , Gene Expression Profiling , Neutrophils/immunology , Neutrophils/metabolism
2.
Nat Immunol ; 21(7): 727-735, 2020 07.
Article in English | MEDLINE | ID: mdl-32541831

ABSTRACT

Stimulator-of-interferon genes (STING) is vital for sensing cytosolic DNA and initiating innate immune responses against microbial infection and tumors. Redox homeostasis is the balance of oxidative and reducing reactions present in all living systems. Yet, how the intracellular redox state controls STING activation is unclear. Here, we show that cellular redox homeostasis maintained by glutathione peroxidase 4 (GPX4) is required for STING activation. GPX4 deficiency enhanced cellular lipid peroxidation and thus specifically inhibited the cGAS-STING pathway. Concordantly, GPX4 deficiency inhibited herpes simplex virus-1 (HSV-1)-induced innate antiviral immune responses and promoted HSV-1 replication in vivo. Mechanistically, GPX4 inactivation increased production of lipid peroxidation, which led to STING carbonylation at C88 and inhibited its trafficking from the endoplasmic reticulum (ER) to the Golgi complex. Thus, cellular stress-induced lipid peroxidation specifically attenuates the STING DNA-sensing pathway, suggesting that GPX4 facilitates STING activation by maintaining redox homeostasis of lipids.


Subject(s)
Herpes Simplex/immunology , Membrane Proteins/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Animals , Carbolines/pharmacology , Cells, Cultured , DNA, Viral/immunology , Disease Models, Animal , Endoplasmic Reticulum/metabolism , Female , Fibroblasts , Golgi Apparatus/metabolism , HEK293 Cells , Herpes Simplex/virology , Herpesvirus 1, Human/genetics , Herpesvirus 1, Human/immunology , Homeostasis/immunology , Humans , Immunity, Innate , Lipid Peroxidation/genetics , Lipid Peroxidation/immunology , Macrophages, Peritoneal/cytology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Membrane Proteins/immunology , Mice , Mice, Knockout , Nucleotidyltransferases/metabolism , Oxidation-Reduction , Oximes/pharmacology , Phospholipid Hydroperoxide Glutathione Peroxidase/antagonists & inhibitors , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Primary Cell Culture , Protein Carbonylation/immunology , Signal Transduction/drug effects , Signal Transduction/immunology , Sulfonamides/pharmacology , THP-1 Cells , Virus Replication/immunology
3.
J Immunol ; 212(2): 295-301, 2024 01 15.
Article in English | MEDLINE | ID: mdl-38054892

ABSTRACT

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) detects cytoplasmic microbial DNA and self-DNA from genomic instability, initiates innate immunity, and plays fundamental roles in defense against viruses and the development of various diseases. The cellular cGAS level determines the magnitude of the response to DNA. However, the underlying mechanisms of the control of cGAS stability, especially its feedback regulation during viral infection, remain largely unknown. In this study, we show that viral infection induces the expression of the UAF1-USP1 deubiquitinase complex in primary peritoneal macrophages (PMs) of C57BL/6J mice. UAF1-USP interacts with cGAS, selectively cleaves its K48-linked polyubiquitination, and thus stabilizes its protein expression in PMs and HEK293T cells. Concordantly, the UAF1-USP1 deubiquitinase complex enhances cGAS-dependent type I IFN responses in PMs. Uaf1 deficiency and ML323 (a specific inhibitor of UAF1-USP1 deubiquitinase complex) attenuates cGAS-triggered antiviral responses and facilitates viral replication both in vitro and in vivo. Thus, our study uncovers a positive feedback mechanism of cGAS-dependent antiviral responses and suggests the UAF1-USP1 complex as a potential target for the treatment of diseases caused by aberrant cGAS activation.


Subject(s)
Ubiquitin-Specific Proteases , Virus Diseases , Animals , Humans , Mice , Antiviral Agents , DNA , HEK293 Cells , Mice, Inbred C57BL , Nuclear Proteins/genetics , Nucleotidyltransferases/genetics , Ubiquitin-Specific Proteases/metabolism
4.
Cereb Cortex ; 34(3)2024 03 01.
Article in English | MEDLINE | ID: mdl-38494891

ABSTRACT

Visual imaging experts play an important role in multiple fields, and studies have shown that the combination of functional magnetic resonance imaging and machine learning techniques can predict cognitive abilities, which provides a possible method for selecting individuals with excellent image interpretation skills. We recorded behavioral data and neural activity of 64 participants during image interpretation tasks under different workloads. Based on the comprehensive image interpretation ability, participants were divided into two groups. general linear model analysis showed that during image interpretation tasks, the high-ability group exhibited higher activation in middle frontal gyrus (MFG), fusiform gyrus, inferior occipital gyrus, superior parietal gyrus, inferior parietal gyrus, and insula compared to the low-ability group. The radial basis function Support Vector Machine (SVM) algorithm shows the most excellent performance in predicting participants' image interpretation abilities (Pearson correlation coefficient = 0.54, R2 = 0.31, MSE = 0.039, RMSE = 0.002). Variable importance analysis indicated that the activation features of the fusiform gyrus and MFG played an important role in predicting this ability. Our study revealed the neural basis related to image interpretation ability when exposed to different mental workloads. Additionally, our results demonstrated the efficacy of machine learning algorithms in extracting neural activation features to predict such ability.


Subject(s)
Brain , Magnetic Resonance Imaging , Humans , Brain/physiology , Magnetic Resonance Imaging/methods , Cognition , Temporal Lobe , Parietal Lobe
5.
J Cell Mol Med ; 28(6): e18164, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38445807

ABSTRACT

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Humans , Mice , Autophagy/genetics , Carcinogenesis/genetics , Carcinoma, Hepatocellular/genetics , Cell Transformation, Neoplastic , Liver Neoplasms/genetics , Membrane Proteins , Mice, Nude
6.
Br J Nutr ; 131(2): 321-332, 2024 01 28.
Article in English | MEDLINE | ID: mdl-37642161

ABSTRACT

Despite observed ethnic differences in eating patterns and obesity, evidence in China is limited. This study examined ethnic differences in eating patterns and their associations with weight outcomes among multi-ethnic adults in West China. A cross-sectional survey collected self-reported data on demographics, eating behaviours, weight and height in 2021. Principal component analysis and multivariate regression were conducted to identify eating patterns and examine their associations with weight outcomes. In total, 4407 subjects aged ≥ 18 years were recruited across seven provinces in West China. Four eating patterns were identified: 'meat-lover' - characterised by frequent consumption of meat and dairy products, 'indulgent' - by frequent intakes of added salt, sugar, alcohol and pickled food, 'diversified-eating' - by frequently consuming food with diversified cooking methods and eating out and 'nutri-health-concerned' - by good food hygiene behaviours and reading food labels. Ethnic differences in eating patterns were observed. Compared with Han, Hui were less likely to exhibit meat-lover or diversified-eating patterns; Tibetans were less likely to have meat-lover or nutri-health-concerned patterns; Mongolians were more likely to have indulgent pattern. BMI was positively associated with meat-lover pattern in both genders (exp(ß): 1·029; 95 % CI: 1·001, 1·058 for men; 1·018; 1·000, 1·036 for women) and negatively associated with nutri-health-concerned pattern in women (0·983; 0·966, 1·000). Mongolians were two times more likely to be overweight/obese than Han (OR: 3·126; 1·688, 5·790). Considerable ethnic differences existed in eating patterns in West China. Mongolians were more likely to be overweight/obese, which was associated with their indulgent eating patterns. Ethnic-specific healthy eating intervention programs are needed.


Subject(s)
Diet , Feeding Behavior , Obesity , Overweight , Adult , Female , Humans , Male , China/epidemiology , Cross-Sectional Studies , Obesity/epidemiology , Ethnicity , East Asian People
7.
Cereb Cortex ; 33(6): 3026-3042, 2023 03 10.
Article in English | MEDLINE | ID: mdl-35764255

ABSTRACT

Ventromedial prefrontal cortex (vmPFC) processes many critical brain functions, such as decision-making, value-coding, thinking, and emotional arousal/recognition, but whether vmPFC plays a role in sleep-wake promotion circuitry is still unclear. Here, we find that photoactivation of dorsomedial hypothalamus (DMH)-projecting vmPFC neurons, their terminals, or their postsynaptic DMH neurons rapidly switches non-rapid eye movement (NREM) but not rapid eye movement sleep to wakefulness, which is blocked by photoinhibition of DMH outputs in lateral hypothalamus (LHs). Chemoactivation of DMH glutamatergic but not GABAergic neurons innervated by vmPFC promotes wakefulness and suppresses NREM sleep, whereas chemoinhibition of vmPFC projections in DMH produces opposite effects. DMH-projecting vmPFC neurons are inhibited during NREM sleep and activated during wakefulness. Thus, vmPFC neurons innervating DMH likely represent the first identified set of cerebral cortical neurons for promotion of physiological wakefulness and suppression of NREM sleep.


Subject(s)
Sleep, REM , Sleep , Sleep/physiology , Sleep, REM/physiology , Arousal , Wakefulness/physiology , GABAergic Neurons/physiology
8.
Eur J Anaesthesiol ; 41(3): 226-233, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38230449

ABSTRACT

BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65 years or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P  = 0.005). Subgroup analysis revealed that age 65-75 years; male sex; ASA III and IV; haemoglobin more than 12 g l -1 ; intra-operative hypotension; surgical duration more than 120 min; and education 9 years or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.


Subject(s)
Acute Kidney Injury , Cardiovascular Infections , Delirium , Emergence Delirium , Stroke , Aged , Humans , Male , Cardiovascular Infections/complications , Delirium/diagnosis , Delirium/epidemiology , Delirium/etiology , Emergence Delirium/diagnosis , Emergence Delirium/epidemiology , Emergence Delirium/etiology , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Risk Factors , Sleep Quality , Female
9.
Chem Biodivers ; 21(5): e202400300, 2024 May.
Article in English | MEDLINE | ID: mdl-38430215

ABSTRACT

Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT-eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4-2-1, Fr.4-2-2 and Fr.4-2-3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K-AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4-2-1 exerted its antioxidant effects by modulating the PI3K/AKT-eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress-induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.


Subject(s)
Flavonoids , Hippophae , Nitric Oxide Synthase Type III , Oxidative Stress , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Hippophae/chemistry , Nitric Oxide Synthase Type III/metabolism , Flavonoids/pharmacology , Flavonoids/isolation & purification , Flavonoids/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effects , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/isolation & purification , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Cell Survival/drug effects , Protective Agents/pharmacology , Protective Agents/chemistry , Protective Agents/isolation & purification
10.
Molecules ; 29(6)2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38542847

ABSTRACT

This study evaluated the effects of four highland barley proteins (HBPs), namely, albumin, globulin, gliadin and glutenin, on the short-term retrogradation of highland barley starch (HBS). The findings reveal that HBPs could reduce the viscosity, storage modulus and hardness of HBS, with albumin and globulin showing more prominent effects. Furthermore, with the addition of HBPs, the loss tangent (tan δ) of HBS loss increased from 0.07 to 0.10, and the enthalpy of gelatinization decreased from 8.33 to 7.23. The degree of retrogradation (DR%) of HBS was 5.57%, and the DR% decreased by 26.65%, 38.78%, 11.67% and 20.29% with the addition of albumin, globulin, gliadin and glutenin, respectively. Moreover, the relative crystallinity (RC) and the double helix structures were inhibited with the HBPs' incorporation. Meanwhile, the HBPs also could inhibit water migration and improve the structure of HBS gels. In summary, HBPs could inhibit the retrogradation behavior of HBS, which provides new theoretical insights for the production studies of highland barley foods.


Subject(s)
Globulins , Hordeum , Starch/chemistry , Gliadin/chemistry , Albumins
11.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1882-1887, 2024 Apr.
Article in Zh | MEDLINE | ID: mdl-38812200

ABSTRACT

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.


Subject(s)
Glycosides , Picrorhiza , Glycosides/chemistry , Glycosides/isolation & purification , Humans , Cell Line, Tumor , Picrorhiza/chemistry , Molecular Structure , Magnetic Resonance Spectroscopy , Drugs, Chinese Herbal/chemistry , Triterpenes
12.
Ann Surg Oncol ; 30(12): 7442-7451, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37326809

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the predictive value of the 5-factor modified frailty index (mFI-5) for postoperative mortality, delirium and pneumonia in patients over 65 years of age undergoing elective lung cancer surgery. METHODS: Data were collected from a single-center retrospective cohort study conducted in a general tertiary hospital from January 2017 to August 2019. In total, the study included 1372 elderly patients aged over 65 who underwent elective lung cancer surgery. They were divided into frail group (mFI-5, 2-5), prefrail group (mFI-5, 1) and robust group (mFI-5, 0) on the basis of mFI-5 classification. The primary outcome was postoperative 1-year all-cause mortality. Secondary outcomes were postoperative pneumonia and postoperative delirium. RESULTS: Frailty group had the highest incidence of postoperative delirium (frailty 31.2% versus prefrailty 1.6% versus robust 1.5%, p < 0.001), postoperative pneumonia (frailty 23.5% versus prefrailty 7.2% versus robust 7.7%, p < 0.001), and postoperative 1-year mortality (frailty 7.0% versus prefrailty 2.2% versus robust 1.9%. p < 0.001). Frail patients have significantly longer length of hospitalization than those in the robust group and prefrail patients (p < 0.001). Multivariate analysis showed a clear link between frailty and increased risk of postoperative delirium (aOR 2.775, 95% CI 1.776-5.417, p < 0.001), postoperative pneumonia (aOR 3.291, 95% CI 2.169-4.993, p < 0.001) and postoperative 1-year mortality (aOR 3.364, 95% CI, 1.516-7.464, p = 0.003). CONCLUSIONS: mFI-5 has potential clinical utility in predicting postoperative death, delirium and pneumonia incidence in elderly patients undergoing radical lung cancer surgery. Frailty screening of patients (mFI-5) may provide benefits in risk stratification, targeted intervention efforts, and assist physicians in clinical decision-making.

13.
BMC Cancer ; 23(1): 973, 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37828456

ABSTRACT

BACKGROUND: Hepatocyte growth factor (HGF) is a peptide-containing multifunctional cytokine, which is overexpressed and/or activated in multiple malignancies and is reported to be associated with tumor development and inferior survival. At present, the role of HGF in small cell lung cancer (SCLC) has not been fully explored yet. MATERIALS AND METHODS: The expression of HGF and its value in predicting survival in SCLC were explored from GEO database and in pan-cancer analysis. Furthermore, we detected the expression of HGF using tumor tissue and paired plasma samples from a validation cohort of 71 SCLC patients at our institute. Correlation between tumor and plasma HGF expression and the prognostic values were analyzed. RESULTS: GEO database analysis revealed that tumor tissue had lower HGF expression than paired normal tissue in SCLC. At our institute, immunohistochemical staining showed negative expression of HGF in tumor tissue of SCLC at our institute (47/47, 100%). The average baseline plasma HGF was 1.28 (range,0.42-4.35) ng/ml. However, plasma HGF was higher in SCLC patients with patients with N3, M1, liver metastasis (LM) and bone metastasis (BM) disease compared with those N0 - 2 (1.25 vs. 1.75 ng/mL, P = 0.000), M0 (1.26 vs. 1.63 ng/mL, P = 0.003), non-LM (1.32 vs. 2.06 ng/mL, P = 0.009), and non-BM (1.35 vs. 1.77 ng/mL, P = 0.047), respectively. Multivariate analysis revealed plasma HGF was an independent predictor for LM and prognostic factor of OS. CONCLUSION: Our results revealed that plasma HGF rather than tumor HGF exhibited a potential role in predicting metastasis and survival in SCLC. Plasma HGF might be used as a non-invasive detecting and monitoring tool for SCLC.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Hepatocyte Growth Factor , Lung Neoplasms/pathology , Signal Transduction , Biomarkers , Prognosis
14.
BMC Cancer ; 23(1): 578, 2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37349714

ABSTRACT

PURPOSE: This study aimed to investigate the clinical utility of diverse aneuploid circulating tumor cell (CTC) subtypes and particularly CTC-associated white blood cell (CTC-WBC) clusters in predicting treatment response, prognosis and real-time monitoring disease progression in advanced driver gene-negative non-small lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 74 eligible patients were prospectively enrolled and serial blood samples were collected at pre-treatment(t0), after two cycles of therapy (t1) and at post-four-to-six treatment cycles (t2). Co-detection of diverse subtypes of aneuploid CTCs and CTC-WBC clusters was conducted in advanced NSCLC patients receiving first-line treatment. RESULTS: At baseline, CTCs were detected in 69 (93.24%) patients and CTC-WBC clusters were detected in 23 (31.08%) patients. Patients with CTCs < 5/6ml or with CTC-WBC clusters undetectable exhibited a better treatment response than patients with pre-therapeutic aneuploid CTCs ≥ 5/6ml or harboring CTC-WBC clusters (p = 0.034 and p = 0.012, respectively). Before treatment, patients bearing tetraploid CTCs ≥ 1/6ml showed significantly inferior progression-free survival (PFS) [hazard ratio (HR):2.420, 95% confidence interval (CI): 1.426-4.106; p = 0.001] and overall survival (OS) compared to patients with tetraploid CTCs < 1/6ml (HR:1.907, 95%CI: 1.119-3.251; p = 0.018). A longitudinal study demonstrated that post-therapeutic patients harboring CTC-WBC clusters displayed the reduced PFS and OS compared with those without CTC-WBC clusters, and subgroup analysis showed that the presence of CTC-WBC clusters indicated a worse prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. After adjusting for multiple significant factors, post-therapeutic CTC-WBC clusters were the only independent predictor of both PFS (HR:2.872, 95% CI: 1.539-5.368; p = 0.001) and OS (HR:2.162, 95% CI: 1.168-4.003; p = 0.014). CONCLUSIONS: In addition to CTCs, longitudinal detection of CTC-WBC clusters provided a feasible tool to indicate initial treatment response, dynamically monitor disease progression and predict survival in driver gene-negative advanced NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neoplastic Cells, Circulating , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Neoplastic Cells, Circulating/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Longitudinal Studies , Tetraploidy , Prognosis , Disease Progression , Biomarkers, Tumor/genetics
15.
Prev Med ; 174: 107607, 2023 09.
Article in English | MEDLINE | ID: mdl-37414227

ABSTRACT

Cardiovascular health (CVH) is closely associated with various noncommunicable diseases (NCDs) and comorbidity; however, the influence of CVH on NCD multimorbidity was not fully elucidated. We aimed to examine the association between CVH using Life's Essential 8 (LE8) and NCD multimorbidity among adults, males, and females in the United States, conducting a cross-sectional analysis using data involving 24,445 participants from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. LE8 was categorized into low, moderate, and high CVH groups. Multivariate logistic regressions and restricted cubic spline regressions were used to estimate the association between LE8 and NCD multimorbidity. Overall, 6162 participants had NCD multimorbidity, of which 1168 (43.5%), 4343 (25.9%), and 651 (13.4%) had low, moderate, and high CVH, separately. After multivariable adjustment, LE8 was negatively associated with NCD multimorbidity among adults (odds ratio (OR) for per 1 standard deviation (SD) increase in LE8 and 95% confidence interval (CI), 0.67 (0.64, 0.69)), and the top 3 NCDs associated with CVH were emphysema, congestive heart failure, stroke, and the dose-response relationships between LE8 and NCD multimorbidity were observed among adults (overall P < 0.001). Similar patterns were also identified among males and females. Higher CVH measured by the LE8 score was associated with lower odds of NCD multimorbidity among adults, males, and females.


Subject(s)
Cardiovascular Diseases , Noncommunicable Diseases , Adult , Male , Female , Humans , United States/epidemiology , Nutrition Surveys , Noncommunicable Diseases/epidemiology , Cross-Sectional Studies , Cardiovascular Diseases/epidemiology , Comorbidity , Risk Factors
16.
J Biomed Inform ; 139: 104303, 2023 03.
Article in English | MEDLINE | ID: mdl-36736449

ABSTRACT

Expert microscopic analysis of cells obtained from frequent heart biopsies is vital for early detection of pediatric heart transplant rejection to prevent heart failure. Detection of this rare condition is prone to low levels of expert agreement due to the difficulty of identifying subtle rejection signs within biopsy samples. The rarity of pediatric heart transplant rejection also means that very few gold-standard images are available for developing machine learning models. To solve this urgent clinical challenge, we developed a deep learning model to automatically quantify rejection risk within digital images of biopsied tissue using an explainable synthetic data augmentation approach. We developed this explainable AI framework to illustrate how our progressive and inspirational generative adversarial network models distinguish between normal tissue images and those containing cellular rejection signs. To quantify biopsy-level rejection risk, we first detect local rejection features using a binary image classifier trained with expert-annotated and synthetic examples. We converted these local predictions into a biopsy-wide rejection score via an interpretable histogram-based approach. Our model significantly improves upon prior works with the same dataset with an area under the receiver operating curve (AUROC) of 98.84% for the local rejection detection task and 95.56% for the biopsy-rejection prediction task. A biopsy-level sensitivity of 83.33% makes our approach suitable for early screening of biopsies to prioritize expert analysis. Our framework provides a solution to rare medical imaging challenges currently limited by small datasets.


Subject(s)
Heart Failure , Heart Transplantation , Humans , Child , Diagnostic Imaging , Machine Learning , Risk Assessment , Postoperative Complications
17.
Gynecol Endocrinol ; 39(1): 2237116, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37489849

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in gynecology with severe metabolic abnormalities. Therefore, identifying effective treatments and drugs for PCOS is important. We aimed to investigate effect of the traditional Chinese medicine (TCM) Rubus chingii Hu (R. chingii) on ovarian function and insulin resistance (IR) of PCOS rat models, and to explore the underlying mechanisms. METHODS: A PCOS rat model was established by subcutaneous injection of dehydroepiandrosterone (DHEA) solution for 20 days. PCOS rats were randomly divided into a control group (CON), model group (MOD), metformin group (MET), TCM R. chingii group (RCG), and RCG + Ad-TXNIP groups. After 28 days of treatment, the samples were collected for subsequent experiments. RESULTS: R. chingii treatment alleviated hormone imbalance and IR while improving ovarian pathology in the PCOS model. R. chingi inhibited the activation of the thioredoxin-interacting protein (TXNIP)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in the ovarian tissue of PCOS rats. Furthermore, TXNIP overexpression hindered the protective effect of R. chingii intervention in PCOS rats, as evidenced by the increase of homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), testosterone (T), C-reactive protein (CRP) levels, and atretic follicles. CONCLUSION: R. chingii intervention improved ovarian polycystic development by suppressing the TXNIP/NLRP3 inflammasome, which may be an effective treatment for PCOS.


Subject(s)
Insulin Resistance , Polycystic Ovary Syndrome , Rubus , Animals , Female , Humans , Rats , Carrier Proteins , Cell Cycle Proteins , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Polycystic Ovary Syndrome/therapy , Rubus/chemistry
18.
Eur Arch Otorhinolaryngol ; 280(4): 1603-1610, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36030467

ABSTRACT

PURPOSE: To assess awareness and recognition of vestibular function tests in otorhinolaryngology medical staffs, especially the vestibular evoked myogenic potentials (VEMP) testing in patients with obstructive sleep apnea (OSA). METHODS: A survey was delivered via either email or a social media app. The medical staffs of the Chinese Medical Association of Otolaryngology Head and Neck Surgery from various branches were enrolled. Study data were collected and managed with an online data collection tool. RESULTS: A total of 1781 emails and 623 social media messages were sent to 2404 otorhinolaryngology medical staffs. One hundred and fifty-seven of them participated in the survey, including 24 via emails and 133 via the social media app. Regarding the knowledge of VEMP, only 59 (37.6%) of them agreed that OSA could be related to vertigo/dizziness/imbalance and 28 (17.8%) believed that OSA could result in VEMP abnormalities and would factor this in diagnosing the impairment of the vestibular function of OSA patients. A total of 7.6% of the respondents had never heard of the VEMP tests. Responses regarding the minimum age at which VEMP are possible ranged from younger than 6 months to greater than 18 years of age. Beliefs regarding the utility and reliability of VEMP varied, with 'unsure' being the most frequent response. In addition, only 17.8% of otolaryngologists indicated some access to the VEMP test. CONCLUSIONS: Knowledge and beliefs about the role of VEMP in diagnosing otolithic organ dysfunction caused by OSA in otorhinolaryngology vary widely. It is important for otorhinolaryngology medical staffs to learn the latest literatures and updated knowledge through continuing education.


Subject(s)
Otolaryngology , Sleep Apnea, Obstructive , Vestibular Evoked Myogenic Potentials , Humans , Infant , Vestibular Evoked Myogenic Potentials/physiology , Reproducibility of Results , Surveys and Questionnaires , Sleep Apnea, Obstructive/diagnosis
19.
Int J Mol Sci ; 24(24)2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38139164

ABSTRACT

Glycyrol (GC) is one natural active product. Imiquimod-induced psoriasis-like Balb/c mouse models were established. The model mice were intraperitoneally injected with cyclosporine A (CsA) and GC for 8 days followed by a series of biological detections. GC had little toxicity according to the levels of peripheral blood cells, hemoglobin, blood urea nitrogen (BUN), and serum creatinine (CRE), while CsA significantly increased the levels of BUN and CRE. GC decreased the splenic index and reduced the expressions of IL-6, IL-23, and CXCL-3 in the model mice and IL-6, CXCL-1, and CXCL-2 in the inflammatory HaCaT cells. The half inhibition concentration (IC50) of GC on HaCaT cells was 29.72 µmol/L, resulting in improved apoptosis, enhanced expressions of p21, BAX, and BIK, and reduced expressions of BCL-2. GC is an immunosuppressive agent against psoriasis-like symptoms by anti-inflammatory effects, which provides a strategy for the discovery of anti-psoriatic natural products.


Subject(s)
Dermatitis , Psoriasis , Mice , Animals , Interleukin-6/metabolism , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/metabolism , Dermatitis/metabolism , Anti-Inflammatory Agents/adverse effects , Inflammation/drug therapy , Inflammation/metabolism , Immunosuppressive Agents/adverse effects , Mice, Inbred BALB C , Disease Models, Animal , Skin/metabolism , Cytokines/metabolism
20.
J Sci Food Agric ; 103(10): 5077-5086, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-36990966

ABSTRACT

BACKGROUND: This study aimed to investigate the effects of semidry milling on the quality attributes of highland barley flour and highland barley bread. Highland barley flours were prepared by dry (DBF), semidry (SBF), and wet (WBF) milling methods. The properties of different highland barley flours were analyzed, and highland barley breads made from different highland barley flours were evaluated. RESULTS: The results showed that WBF had the lowest damaged starch content (15.2 g kg-1 ), and the contents of damaged starch in SBF-35 and SBF-40 (43.5 g kg-1 and 24.1 g kg-1 respectively) were lower than that of DBF (87.6 g kg-1 ). And SBF-35 and SBF-40 with large particles exhibited low hydration performance. In addition, SBF-35 and SBF-40 had higher pasting viscosity, pasting temperature, ΔH, and relative crystallinity, consequently resulting in better gel properties than other highland barley flours. These properties could help SBF-35 and SBF-40 develop high-quality bread with large specific volume and superior crumb structure and texture that is similar to the bread with WBF. CONCLUSION: Overall, semidry milling not only could improve the characteristics of HBF, but also avoid high starch damage by dry milling and water wasting by wet milling. What is more, highland barley breads with SBF-35 and SBF-40 had preferable appearance and crumb texture. Therefore, semidry milling could be regarded as a feasible way to produce highland barley flour. © 2023 Society of Chemical Industry.


Subject(s)
Flour , Hordeum , Bread , Hordeum/chemistry , Starch/chemistry , Water
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