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BACKGROUND: Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative disorders characterized by α-synuclein pathology, disrupted iron homeostasis and impaired neurochemical transmission. Considering the critical role of iron in neurotransmitter synthesis and transport, our study aims to identify distinct patterns of whole-brain iron accumulation in MSA and PD, and to elucidate the corresponding neurochemical substrates. METHODS: A total of 122 PD patients, 58 MSA patients and 78 age-, sex-matched health controls underwent multi-echo gradient echo sequences and neurological evaluations. We conducted voxel-wise and regional analyses using quantitative susceptibility mapping to explore MSA or PD-specific alterations in cortical and subcortical iron concentrations. Spatial correlation approaches were employed to examine the topographical alignment of cortical iron accumulation patterns with normative atlases of neurotransmitter receptor and transporter densities. Furthermore, we assessed the associations between the colocalization strength of neurochemical systems and disease severity. RESULTS: MSA patients exhibited increased susceptibility in the striatal, midbrain, cerebellar nuclei, as well as the frontal, temporal, occipital lobes, and anterior cingulate gyrus. In contrast, PD patients displayed elevated iron levels in the left inferior occipital gyrus, precentral gyrus, and substantia nigra. The excessive iron accumulation in MSA or PD correlated with the spatial distribution of cholinergic, noradrenaline, glutamate, serotonin, cannabinoids, and opioid neurotransmitters, and the degree of this alignment was related to motor deficits. CONCLUSIONS: Our findings provide evidence of the interaction between iron accumulation and non-dopamine neurotransmitters in the pathogenesis of MSA and PD, which inspires research on potential targets for pharmacotherapy.
Subject(s)
Multiple System Atrophy , Parkinson Disease , Humans , Multiple System Atrophy/metabolism , Multiple System Atrophy/diagnostic imaging , Multiple System Atrophy/pathology , Parkinson Disease/metabolism , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Male , Female , Middle Aged , Aged , Brain/metabolism , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Iron/metabolism , Neurotransmitter Agents/metabolism , Brain Mapping/methodsABSTRACT
Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging on the temporal dynamics of a large-scale functional network in PD. We enrolled 62 PD patients and 32 healthy controls (HCs). The level of brain aging was determined by calculating global and local brain age gap estimates (G-brainAGE and L-brainAGE) from structural images. The neural network activity of the whole brain was captured by identifying coactivation patterns (CAPs) from resting-state functional images. Intergroup differences were assessed using the general linear model. Subsequently, a spatial correlation analysis between the L-brainAGE difference map and CAPs was conducted to uncover the anatomical underpinnings of functional alterations. Compared to HCs (-3.73 years), G-brainAGE was significantly higher in PD patients (+1.93 years), who also exhibited widespread elevation in L-brainAGE. G-brainAGE was correlated with disease severity and duration. PD patients spent less time in CAPs involving activated default mode and the fronto-parietal network (DMN-FPN), as well as the sensorimotor and salience network (SMN-SN), and had a reduced transition frequency from other CAPs to the DMN-FPN and SMN-SN CAPs. Furthermore, the pattern of localized brain age acceleration showed spatial similarities with the SMN-SN CAP. Accelerated structural brain aging in PD adversely affects brain function, manifesting as dysregulated brain network dynamics. These findings provide insights into the neuropathological mechanisms underlying neurodegenerative diseases and imply the possibility of interventions for modifying PD progression by slowing the brain aging process.
Subject(s)
Aging , Brain , Magnetic Resonance Imaging , Parkinson Disease , Humans , Parkinson Disease/physiopathology , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Male , Female , Middle Aged , Aging/physiology , Aging/pathology , Brain/diagnostic imaging , Brain/physiopathology , Aged , Nerve Net/diagnostic imaging , Nerve Net/physiopathologyABSTRACT
BACKGROUND: For chronic hepatitis B virus (HBV) infection patients, increasing evidence has demonstrated the effectiveness of expanding the indications and applicable population for antiviral therapy. However, the expanded indication of antiviral therapy for hepatocellular carcinoma (HCC) remains to be further explored. METHODS: 196 HBV-related HCC patients who received radical hepatectomy and nucleos(t)ide analogues (NAs) therapy at Sichuan Provincial People's Hospital were enrolled in this study. HCC recurrence, overall survival (OS), early virological (VR) and biochemical responses (BR) of patients were compared between different NAs therapy and the use of anti-programmed cell death protein 1 (PD-1) therapy. RESULTS: NAs therapy at different timing of surgery was a strong independent risk factor for postoperative recurrence and overall mortality of HBV-related HCC patients. Furthermore, in HCC patients who received postoperative anti-PD-1 therapy, patients with HBV DNA < 1000 copy/mL had significantly better recurrence-free survival (RFS) and OS than those with HBV DNA ≥ 1000 copy/mL (HR: 7.783; P = 0.002; HR: 6.699; P < 0.001). However, the differences of RFS and OS rates between entecavir group and tenofovir disoproxil fumarate group were not statistically significant. Similar results were also observed in the rates of early VR, BR and combined VR and BR. CONCLUSION: Timely and reasonable preoperative NAs therapy showed clinical benefit in improving the prognosis of patients with HBV-related HCC, even in the case of normal alanine aminotransferase (ALT) level and negative hepatitis e antigen (HBeAg). Furthermore, a possible synergistic effect between antiviral therapy and anti-PD-1 therapy was founded and need further verification.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/surgery , Hepatitis B virus , DNA, Viral , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Prognosis , Antiviral Agents/therapeutic useABSTRACT
PURPOSE: To evaluate the performance of multi-pool Chemical exchange saturation transfer (CEST) MRI in prediction of glioma grade, isocitrate dehydrogenase (IDH) mutation, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss and Ki-67 labeling index (LI), based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5). METHODS: 95 patients with adult-type diffuse gliomas were analyzed. The amide, direct water saturation (DS), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer (MT) and amine signals were derived using Lorentzian fitting, and asymmetry-based amide proton transfer-weighted (APTwasym) signal was calculated. The mean value of tumor region was measured and intergroup differences were estimated using student-t test. The receiver operating curve (ROC) and area under the curve (AUC) analysis were used to evaluate the diagnostic performance of signals and their combinations. Spearman correlation analysis was performed to evaluate tumor proliferation. RESULTS: The amide and DS signals were significantly higher in high-grade gliomas compared to low-grade gliomas, as well as in IDH-wildtype gliomas compared to IDH-mutant gliomas (all p < 0.001). The DS, MT and amine signals showed significantly differences between ATRX loss and retention in grade 2/3 IDH-mutant gliomas (all p < 0.05). The combination of signals showed the highest AUC in prediction of grade (0.857), IDH mutation (0.814) and ATRX loss (0.769). Additionally, the amide and DS signals were positively correlated with Ki-67 LI (both p < 0.001). CONCLUSION: Multi-pool CEST MRI demonstrated good potential to predict glioma grade, IDH mutation, ATRX loss and Ki-67 LI.
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BACKGROUND: Resection of colorectal adenoma (CRA) prevents colorectal cancer; however, recurrence is common. We aimed to assess the association of the triglyceride-glucose (TyG) index with CRA occurrence and recurrence. METHODS: Data from 3392 participants at a hospital in China from 2020 to 2022 were analyzed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A restricted cubic spline was used to fit TyG index doseâresponse curves to recurrent adenomas. The discriminatory power of TyG index for predicting later recurrence was assessed with the area under the receiver operating characteristic (ROC) curve in 170 patients with a TyG index at initial adenoma diagnosis. RESULTS: One thousand five hundred ninety-six adenoma and 1465 normal participants were included in the occurrence analysis, and 179 recurrent and 152 nonrecurrent participants were included in the recurrence analysis. The TyG mutation was an independent risk factor for CRA occurrence and recurrence. After adjusting for confounders, the risk of adenoma in the participants in Q2, Q3, and Q4 groups of TyG was 1.324 (95% CI 1.020-1.718), 1.349 (95% CI 1.030-1.765), and 1.445 (95% CI 1.055-1.980) times higher than that of the Q1, respectively, and the risk of recurrence in the Q3 and Q4 groups was 2.267 (95% CI 1.096-4.691) and 2.824 (95% CI 1.199-6.648) times in Q1 group. Multiple logistic regression showed that the highest quartile of the TyG index was associated with a greater risk of advanced adenoma recurrence (OR 4.456, 95% CI 1.157-17.164), two or more adenomas (OR 5.079, 95% CI 1.136-22.714 [after removal of TyG index extreme values]), and proximal colon or both adenomas (OR 3.043, 95% CI 1.186-7.810). Subgroup analysis revealed that the association was found to be present only in participants of all age groups who were either male or without obesity, hyperglycemia, hypertension, or dyslipidemia (p < 0.05). ROC curves illustrated that the TyG index had good predictive efficacy for identifying recurrence, especially for patients with two or more adenomas (AUC 0.777, 95% CI 0.648-0.907). CONCLUSIONS: An increase in the TyG index is associated with an increased risk of adenoma occurrence and recurrence, with a stronger association with the latter.
Subject(s)
Adenoma , Carbamates , Colorectal Neoplasms , Pyrazines , Pyridines , Humans , Male , Glucose , Retrospective Studies , Adenoma/epidemiology , China/epidemiology , Colorectal Neoplasms/epidemiology , Triglycerides , Blood Glucose , Risk Factors , BiomarkersABSTRACT
Although aerobic composting is usually utilized in livestock manure disposal, the emission of odorous gases from compost not only induces harm to the human body and the environment, but also causes loss of nitrogen, sulfur, and other essential elements, resulting in a decline in product quality. The impact of biotrickling filter (BTF) and insertion of carbon-based microbial agent (CBMA) on compost maturation, odor emissions, and microbial population during the chicken manure composting were assessed in the current experiment. Compared with the CK group, CBMA addition accelerated the increase in pile temperature (EG group reached maximum temperature 10 days earlier than CK group), increased compost maturation (GI showed the highest increase of 41.3% on day 14 in EG group), resulted in 36.59% and 14.60% increase in NO3--N content and the total nitrogen retention preservation rate after composting. The deodorization effect of biotrickling filter was stable, and the removal rates of NH3, H2S, and TVOCs reached more than 90%, 96%, and 56%, respectively. Furthermore, microbial sequencing showed that CBMA effectively changed the microbial community in compost, protected the ammonia-oxidizing microorganisms, and strengthened the nitrification of the compost. In addition, the nitrifying and denitrifying bacteria were more active in the cooling period than they were in the thermophilic period. Moreover, the abundance of denitrification genes containing nirS, nirK, and nosZ in EG group was lower than that in CK group. Thus, a large amount of nitrogen was retained under the combined drive of BTF and CBMA during composting. This study made significant contributions to our understanding of how to compost livestock manure while reducing releases of odors and raising compost quality.
Subject(s)
Agricultural Inoculants , Composting , Animals , Humans , Manure/microbiology , Chickens , Odorants , Nitrogen/analysis , Carbon , SoilABSTRACT
Objective: It was to investigate the diagnosis of fetal hemodynamics in pregnant women with diabetes mellitus in the third trimester of pregnancy by color Doppler ultrasonography. Methods: 55 women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy who were clinically diagnosed and treated in Haian City People's Hospital of Jiangsu Province were selected as the observation group, and 55 pregnant women with normal prenatal examination results were selected as the controls. The hemodynamic parameters of fetal middle cerebral artery (MCA), umbilical artery (UA), and renal artery (RA) were detected, including the ratio of maximum systolic blood flow velocity to end-diastolic blood flow velocity (S/D), resistance index (RI) and arterial pulsation index (PI). Fasting serum levels of maternal patients were collected for detecting Cystain C (Cys C) and homocysteine (Hcy) to analyze the predictive value of serological indexes and target arterial hemodynamics parameters for adverse pregnancy outcome (APO). Results: The results showed that compared with controls, in the observation group, RI, PI, and S/D of MCA and RA increased significantly, while RI, PI and S/D of UA decreased obviously (P < 0.05), the levels of serum Cys C and Hcy were clearly increased (P < 0.05). The APO rate of controls and observation group was 10.91 % and 25.45 %, respectively. It was found that the area under the curve of serum Cys C, Hcy, and the APO predicted by the hemodynamic parameters of fetal MCA, UA, and RA were all greater than 0.75 (P < 0.05). Multiple Logistic regression analysis showed that serum Cys C and Hcy, and the hemodynamic parameters of fetal MCA, UA and RA were correlated with APO (P < 0.05). Conclusion: In summary, maternal blood glucose level can affect fetal hemodynamic parameters. In the third trimester of pregnancy, the changes of blood flow parameters of fetal MCA, UA, RA, and maternal serum Cys C and Hcy levels are helpful to understand fetal status in utero, and can be used to predict APO.
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In response to the escalating demand for real-time and accurate fault detection in power transmission lines, this paper undertook an optimization of the existing YOLOv4 network. This involved the substitution of the main feature extraction network within the original YOLOv4 model with a lighter EfficientNet network. Additionally, the inclusion of Grouped Convolution modules in the feature pyramid structure replaced conventional convolution operations. The resulting model not only reduced model parameters but also effectively ensured detection accuracy. Moreover, in enhancing the model's reliability, data augmentation techniques were employed to bolster the robustness of the power transmission line fault detection algorithm. This optimization further utilized the DIoU loss function to stabilize target box regression. Comparative experiments demonstrated the improved YOLOv4 model's superior performance in terms of loss function optimization while significantly enhancing detection speed under equivalent configurations. The parameter capacity was reduced by 81%, totaling merely 43.65 million, while the frame rate surged by 85% to achieve 24 frames per second. These experimental findings validate the effectiveness of the algorithm.
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INTRODUCTION: The aim of the study was to explore the value of serum procalcitonin to albumin (PCT/ALB) and C-reactive protein to albumin (CRP/ALB) ratios in evaluating the condition and prognosis of craniocerebral trauma (CT). MATERIAL AND METHODS: 158 patients with CT admitted to the emergency department of our hospital from January 2020 to June 2022 were selected as the study subjects. According to the Glasgow coma scale (GCS) score, 158 patients with CT were grouped in a mild group (GCS score 13-15 points, n = 68), a moderate group (GCS score 9-12 points, n = 61), and a severe group (GCS score 3-8 points, n = 29). Besides, according to the patient's Glasgow prognosis (GOS) score, 158 patients with CT were divided into a good prognosis group (GOS score 4-5 points, n = 110) and a poor prognosis group (GOS score 1-3 points, n = 48). Serum PCT/ALB and CRP/ALB levels of different groups were compared. The correlation between PCT/ALB and CRP/ALB ratios and the score of GCS and GOS was explored using Pearson correlation analysis. Prognosis-related influencing factors were found out through multivariate logistic regression. The value of serum PCT/ALB and CRP/ALB ratios in evaluating the condition and prognosis of CT was evaluated by the ROC curve. RESULTS: Patients in the moderate and severe groups had much higher ratios of PCT/ALB and CRP/ALB and sharply lower GCS scores than those in the mild group ( p < 0.001). Compared with the patients in the moderate group, those in the severe group had much higher PCT/ALB and CRP/ALB ratios and obviously lower GCS scores ( p < 0.001). Patients with poor prognosis had markedly higher PCT/ALB and CRP/ALB ratios and memorably lower GOS score than the patients with good prognosis ( p < 0.001). A negative correlation between PCT, CRP, PCT/ALB ratio, CRP/ALB ratio and GCS scores ( r = -0.821, -0.857, -0.750, -0.766, p < 0.001) and GOS scores ( r = -0.636, -0.628, -0.595, -0.628, p < 0.001) was revealed by Pearson correlation analysis. ALB was correlated positively with GCS score and GOS score ( r = 0.381, 0.413, p < 0.001). Multivariate logistic regression analysis exhibited that PCT/ALB ratio and CRP/ALB ratio were related to poor prognosis of CT patients ( p < 0.05). ROC curve analysis showed that the combined PCT/ALB ratio and CRP/ALB area under the curve (AUC) were 0.883 and 0.860, respectively, which were used to assess the severity and predict prognosis of patients with CT. CONCLUSIONS: PCT/ALB and CRP/ALB ratios were positively correlated with the severity and prognosis of patients with CT, and were risk factors for poor prognosis. Early determination of changes in PCT/ALB and CRP/ALB ratios had a certain clinical value for evaluating the condition and prognosis of CT patients.
Subject(s)
C-Reactive Protein , Craniocerebral Trauma , Procalcitonin , Humans , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Prognosis , Male , Female , Craniocerebral Trauma/blood , Middle Aged , Adult , Procalcitonin/blood , Glasgow Coma Scale , Aged , Serum Albumin/analysis , Biomarkers/blood , Young AdultABSTRACT
Peripheral nerve injury (PNI) represents a serious clinical and public health problem due to its high incurrence and poor spontaneous recovery. Compared to autograft, which is still the best current practice for long-gap peripheral nerve defects in clinics, the use of polymer-based biodegradable nerve guidance conduits (NGCs) has been gaining momentum as an alternative to guide the repair of severe PNI without the need of secondary surgery and donor nerve tissue. However, simple hollow cylindrical tubes can barely outperform autograft in terms of the regenerative efficiency especially in critical sized PNI. With the rapid development of tissue engineering technology and materials science, various functionalized NGCs have emerged to enhance nerve regeneration over the past decades. From the aspect of scaffold design considerations, with a specific focus on biodegradable polymers, this review aims to summarize the recent advances in NGCs by addressing the onerous demands of biomaterial selections, structural designs, and manufacturing techniques that contributes to the biocompatibility, degradation rate, mechanical properties, drug encapsulation and release efficiency, immunomodulation, angiogenesis, and the overall nerve regeneration potential of NGCs. In addition, several commercially available NGCs along with their regulation pathways and clinical applications are compared and discussed. Lastly, we discuss the current challenges and future directions attempting to provide inspiration for the future design of ideal NGCs that can completely cure long-gap peripheral nerve defects.
Subject(s)
Nerve Regeneration , Peripheral Nerve Injuries , Tissue Scaffolds , Nerve Regeneration/physiology , Humans , Animals , Peripheral Nerve Injuries/therapy , Peripheral Nerves/physiology , Biocompatible Materials , Tissue Engineering/methods , Tissue Engineering/trends , Guided Tissue Regeneration/methods , Guided Tissue Regeneration/trends , Guided Tissue Regeneration/instrumentationABSTRACT
Objective: The purpose of this manuscript is to identify longitudinal trajectories of changes in triglyceride glucose (TyG) index and investigate the association of TyG index trajectories with risk of lean nonalcoholic fatty liver disease (NAFLD). Methods: Using data from 1,109 participants in the Health Management Cohort longitudinal study, we used Latent Class Growth Modeling (LCGM) to develop TyG index trajectories. Using a Cox proportional hazard model, the relationship between TyG index trajectories and incident lean NAFLD was analyzed. Restricted cubic splines (RCS) were used to visually display the dose-response association between TyG index and lean NAFLD. We also deployed machine learning (ML) via Light Gradient Boosting Machine (LightGBM) to predict lean NAFLD, validated by receiver operating characteristic curves (ROCs). The LightGBM model was used to create an online tool for medical use. In addition, NAFLD was assessed by abdominal ultrasound after excluding other liver fat causes. Results: The median age of the population was 46.6 years, and 440 (39.68%) of the participants were men. Three distinct TyG index trajectories were identified: "low stable" (TyG index ranged from 7.66 to 7.71, n=206, 18.5%), "moderate stable" (TyG index ranged from 8.11 to 8.15, n=542, 48.8%), and "high stable" (TyG index ranged from 8.61 to 8.67, n=363, 32.7%). Using a "low stable" trajectory as a reference, a "high stable" trajectory was associated with an increased risk of lean-NAFLD (HR: 2.668, 95% CI: 1.098-6.484). After adjusting for baseline age, WC, SBP, BMI, and ALT, HR increased slightly in "moderate stable" and "high stable" trajectories to 1.767 (95% CI:0.730-4.275) and 2.668 (95% CI:1.098-6.484), respectively. RCS analysis showed a significant nonlinear dose-response relationship between TyG index and lean NAFLD risk (χ2 = 11.5, P=0.003). The LightGBM model demonstrated high accuracy (Train AUC 0.870, Test AUC 0.766). An online tool based on our model was developed to assist clinicians in assessing lean NAFLD risk. Conclusion: The TyG index serves as a promising noninvasive marker for lean NAFLD, with significant implications for clinical practice and public health policy.
Subject(s)
Non-alcoholic Fatty Liver Disease , Male , Humans , Middle Aged , Female , Longitudinal Studies , Glucose , Machine Learning , TriglyceridesABSTRACT
Neuromelanin hypopigmentation within substantia nigra pars compacta (SNc) reflects the loss of pigmented neurons, which in turn contributes to the dysfunction of the nigrostriatal and striato-cortical pathways in Parkinson's disease (PD). Our study aims to investigate the relationships between SN degeneration manifested by neuromelanin reduction, functional connectivity (FC) among large-scale brain networks, and motor impairment in PD. This study included 68 idiopathic PD patients and 32 age-, sex- and education level-matched healthy controls who underwent neuromelanin-sensitive magnetic resonance imaging (MRI), functional MRI, and motor assessments. SN integrity was measured using the subregional contrast-to-noise ratio calculated from neuromelanin-sensitive MRI. Resting-state FC maps were obtained based on the independent component analysis. Subsequently, we performed partial correlation and mediation analyses in SN degeneration, network disruption, and motor impairment for PD patients. We found significantly decreased neuromelanin within SN and widely altered inter-network FCs, mainly involved in the basal ganglia (BG), sensorimotor and frontoparietal networks in PD. In addition, decreased neuromelanin content was negatively correlated with the dorsal sensorimotor network (dSMN)-medial visual network connection (P = 0.012) and dSMN-BG connection (P = 0.004). Importantly, the effect of SN neuromelanin hypopigmentation on motor symptom severity in PD is partially mediated by the increased connectivity strength between BG and dSMN (indirect effect = - 1.358, 95% CI: - 2.997, - 0.147). Our results advanced our understanding of the interactions between neuromelanin hypopigmentation in SN and altered FCs of functional networks in PD and suggested the potential of multimodal metrics for early diagnosis and monitoring the response to therapies.
Subject(s)
Hypopigmentation , Motor Disorders , Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/pathology , Substantia Nigra/metabolism , Melanins/metabolism , Magnetic Resonance Imaging/methods , Hypopigmentation/metabolism , Hypopigmentation/pathologyABSTRACT
BACKGROUND: Periodontitis is a chronic progressive disease and the leading cause of tooth loss in adults. Recent studies have shown the impact of oral microbial communities on systemic health and diseases such as cancer, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, diabetes, hypertension, and Alzheimer's disease. In previous case control studies investigatin the relationship between periodontal disease and the oral microbiota, little attention has been paid to the intersections of these domains. METHODS: Here, we used high-throughput 16S rRNA sequencing to analyse the differences in the microbial composition in saliva between a group of patients with chronic periodontitis (C; n = 51) and a healthy control group (H; n = 61) and predicted the functional gene composition by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. RESULTS: We found significant alterations in oral microbial diversity between C and H (P = 0.002). Sixteen genera were significantly different between C and H, and 15 of them were enriched in C linear discriminant analysis (LDA > 2). Fifty functional genes were significantly different between C and H, and 34 of them were enriched in C (P < .025). CONCLUSIONS: Periodontitis is associated with significant changes in the oral microbial community.
Subject(s)
Chronic Periodontitis , Microbiota , RNA, Ribosomal, 16S , Saliva , Humans , RNA, Ribosomal, 16S/genetics , Chronic Periodontitis/microbiology , Chronic Periodontitis/genetics , Case-Control Studies , Male , Female , Saliva/microbiology , Middle Aged , Microbiota/genetics , Adult , PhylogenyABSTRACT
OBJECTIVE: To characterize the retinal microvasculature and structure in subjective cognitive decline (SCD) and identify the potential biomarker for the early stage of the Alzheimer's disease (AD) spectrum. METHODS: In this study, 35 patients with SCD, 36 with cognitive impairment, and 29 with normal cognition (NC) were enrolled. Optical coherence tomography angiography was employed to assess retinal vascular density, fovea avascular zone area, and retinal thickness. The parameters reflecting retinal perfusion and structure were compared among the three groups. In addition, the association between retinal parameters, cerebral blood flow (CBF), and peripheral blood biomarkers in the SCD stage was analyzed. RESULTS: The superficial vascular complex (SVC) vascular density in the macula and retinal nerve fiber layer thickness in the peripapillary were significantly reduced in individuals with SCD compared to NC. Furthermore, there was a positive correlation between macular ganglion cell complex thickness and CBF in SCD. INTERPRETATION: The retinal microvasculature and structure exhibit alterations in individuals with SCD. Macular ganglion cell complex thickness demonstrates correlations with cerebral perfusion. The retina holds potential as a novel biomarker for early detection of AD.
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BACKGROUND: Within the normal range, elevated alanine aminotransferase (ALT) levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). AIM: To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively. METHODS: A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected. The incidence rate, cumulative times, and equally and unequally weighted cumulative effects of excess high-normal ALT levels (ehALT) were measured. Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD. RESULTS: A total of 83.13% of participants with MAFLD had normal ALT levels. The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group. Compared with those in the low-normal ALT group, the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651 [95% confidence interval (CI): 1.199-2.273] and 1.535 (95%CI: 1.119-2.106) in the third quartile and 1.616 (95%CI: 1.162-2.246) and 1.580 (95%CI: 1.155-2.162) in the fourth quartile, respectively. CONCLUSION: Most participants with MAFLD had normal ALT levels. Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Alanine Transaminase , China/epidemiology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Physical Examination , Reference ValuesABSTRACT
Ischemiaâreperfusion (I/R) injury is a frequently observed complication after flap surgery, and it affects skin flap survival and patient prognosis. Currently, there are no proven safe and effective treatment options to treat skin flap I/R injury. Herein, the potential efficacies of the bioactive peptide from maggots (BPM), as well as its underlying mechanisms, were explored in a rat model of skin flap I/R injury and LPS- or H2O2-elicited RAW 264.7 cells. We demonstrated that BPM significantly ameliorated the area of flap survival, and histological changes in skin tissue in vivo. Furthermore, BPM could markedly restore or enhance Nrf2 and HO-1 levels, and suppress the expression of pro-inflammatory cytokines, including TLR4, p-IκB, NFκB p65, p-p65, IL-6, and TNF-α in I/R-injured skin flaps. In addition, BPM treatment exhibited excellent biocompatibility with an adequate safety profile, while it exhibited superior ROS-scavenging ability and the upregulation of antioxidant enzymes in vitro. Mechanistically, the above benefits related to BPM involved the activation of Nrf2/HO-1 and suppression of TLR4/NF-κB pathway. Taken together, this study may provide a scientific basis for the potential therapeutic effect of BPM in the prevention of skin flap I/R injury and other related diseases.
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Objective: We aimed to examine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) affects the lung fibrosis process through the activation of p38 protein in mitogen-activated protein kinases (MAPK) signaling pathway, as well as the expression of downstream inflammatory factors. Methods: The expression levels of HB-EGF, collagen type I (COL-I), and hexokinase 2 (HK2) in peripheral blood mononuclear cells (PBMCs) of patients with connective tissue disease-related interstitial lung disease (CTD-ILD) were examined by qPCR, Western blotting and ELISA. Results: In vitro experiments showed that HB-EGF was increased in almost all subtypes [rheumatoid arthritis (RA), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIMs)] as well as in all groups (P < 0.05). For embryonic lung fibroblast (A549) cells, the expression levels of HK2 and α-smooth muscle actin (α-SMA) genes were elevated during 0-4 h and then plateaued. Transforming growth factor-ß1 (TGF-ß1) induced fibrosis in human embryonic lung fibroblasts (MRC-5) cells and A549 for a certain period of time, but the degree of induction varied, which may be related to the redifferentiability of cells at different spatial locations. Moreover, HB-EGF at concentrations above 1 ng/ml stimulation increased COL-I expression (P < 0.05), and for α-SMA gene, even 1 ng/ml concentration of HB-EGF had a stimulatory effect, and different concentrations of HB-EGF did activate the expression of p38 in a concentration-dependent manner within a certain concentration range, and by The qPCR results showed that for interleukin 6 (IL-6), an inflammatory factor regulated downstream of p38, the expression was significantly increased in A549 cells compared to control (P < 0.05), but tumor necrosis factor-α (TNF-α) expression was downregulated (P < 0.05), but for interleukin-1ß (IL-1ß) gene, there was no significant difference in A549 cells, and expression was downregulated in MRC-5 cells. Therefore, it is suggested that HB-EGF regulates the expression of inflammatory factors through p38 will be differential across cells. Conclusion: Our study shows that HB-EGF can suppress pulmonary fibrosis through downstream activation of p38/MAPK pathway activity, as well as the expression of various inflammatory factors downstream of it.
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Purpose: To compare the antireflux effect, long-term nutritional levels, and quality of life (QoL) between laparoscopy-assisted proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction (LTG-RY) for adenocarcinoma of the esophagogastric junction (AEG). Methods: This multicenter retrospective cohort study collected clinicopathological and follow-up data of AEG patients from January 2016 to January 2021 at five high-volume surgery centers. The study included patients who underwent digestive tract reconstruction with LPG-DTR or LTG-RY after tumor resection. Propensity score matching (PSM) was utilized to minimize confounding factors. The comparison after PSM included postoperative complications, reflux esophagitis, long-term nutritional levels, and QoL. Results: A total of 151 consecutive patients underwent either LPG-DTR or LTG-RY. After PSM, 50 patients from each group were included in the analysis. The frequency of reflux esophagitis and Clavien-Dindo classification did not significantly differ between the two groups (P > 0.05). At 1 year after surgery, the LPG-DTR group showed significantly higher weight and hemoglobin levels than the LTG-RY group (P < 0.05). The overall postoperative Visick grade differed significantly between the groups (P < 0.05), but there was no significant difference in the proportion of patients with Visick≥III (P > 0.05). Conclusion: Both LPG-DTR and LTG-RY are safe and feasible methods for digestive tract reconstruction in patients with AEG. Both methods have similar antireflux effects and postoperative QoL. However, LPG-DTR resulted in superior nutritional levels compared to LTG-RY. Therefore, LPG-DTR is considered a relatively effective method for digestive tract reconstruction in AEG patients.
ABSTRACT
Designing active and stable electrocatalysts with economic efficiency for oxygen evolution reaction (OER) is essential for developing water splitting process at an industrial scale. Herein, we rationally designed a tungsten doped iron cobalt phosphide incorporated with carbon (Wx-FeCoP2/C), prepared by a mechanochemical approach. X-ray photoelectron spectroscopy (XPS) revealed that the doping of W led to an increasing of Co3+/Co2+ and Fe3+/Fe2+ molar ratios, which contributed to the enhanced OER performance. As a result, a current density of 10 mA cm-2 was achieved in 1 M KOH at an overpotential of 264 mV on the optimized W0.1-FeCoP2/C. Moreover, at high current density of 100 mA cm-2, the overpotential value was 310 mV, and the corresponding Tafel slope was measured to be 48.5 mV dec-1, placing it among the best phosphide-based catalysts for OER. This work is expected to enlighten the design strategy of highly efficient phosphide-based OER catalysts.