ABSTRACT
Circadian rhythm disruption is closely related to increased incidence of prostate cancer. Incorporating circadian rhythms into the study of prostate cancer pathogenesis can provide a more comprehensive understanding of the causes of cancer and offer new options for precise treatment. Therefore, this article comprehensively summarizes the epidemiology of prostate cancer, expounds the contradictory relationship between circadian rhythm disorders and prostate cancer risk, and elucidates the relationship between circadian rhythm regulators and the incidence of prostate cancer. Importantly, this article also focuses on the correlation between circadian rhythms and androgen receptor signaling pathways, as well as the applicability of time therapy in prostate cancer. This may prove significant in enhancing the clinical treatment of prostate cancer.
ABSTRACT
National assessments of groundwater contamination risks are crucial for sustaining high-quality groundwater supplies. However, traditional methods often treat groundwater contamination risk as a steady-state indicator without considering spatiotemporal variation in risk, both geographically and over time, caused by anthropogenic and climatic factors. In this work, XGBoost, a tree-based algorithm, was applied to comprehensively analyze the drivers of groundwater contamination from nitrate, using data on 13 physical features (as used by the index-based ranking method DRASTIC) and 30 anthropogenic features from 1985 to 2010 in the contiguous United States (CONUS). The results indicate that physical features controlling the transport processes, particularly those affecting contaminant travel time from land surface to groundwater (depth to water table and transmissivity), were the dominant factors for nitrate contamination in groundwater. This was followed by features representing the potential nitrogen loading. Positive correlations between most features and the nitrogen loading time (year) were found, suggesting their growing influence on contamination risk. Based on the drivers identified for nitrate concentrations exceeding 10 mg/L in groundwater and their varying temporal contributions, this study proposes a reformulated index-based method for contamination risk assessment. With this method, an overall accuracy of around 70 % was achieved based on the validation data set. The predicted high-risk areas are mainly intensive irrigation regions, such as the High Plains, northern Midwest, and Central Valley. This new approach contributes to a more accurate and effective assessment of the contamination risks of groundwater on a regional and national scale under temporally varying environmental conditions.
ABSTRACT
Autistic individuals generally demonstrate impaired emotion recognition but it is unclear whether effects are emotion-specific or influenced by oxytocin receptor (OXTR) genotype. Here we implemented a dimensional approach using an implicit emotion recognition task together with functional MRI in a large cohort of neurotypical adult participants (N = 255, male = 131, aged 17-29 years) to establish associations between autistic traits and neural and behavioral responses to specific face emotions, together with modulatory effects of OXTR genotype. A searchlight-based multivariate pattern analysis (MVPA) revealed an extensive network of frontal, basal ganglia, cingulate and limbic regions exhibiting significant predictability for autistic traits from patterns of responses to angry relative to neutral expression faces. Functional connectivity analyses revealed a genotype interaction (OXTR SNPs rs2254298, rs2268491) for coupling between the orbitofrontal cortex and mid-cingulate during angry expression processing, with a negative association between coupling and autistic traits in the risk-allele group and a positive one in the non-risk allele group. Overall, results indicate extensive emotion-specific associations primarily between patterns of neural responses to angry faces and autistic traits in regions processing motivation, reward and salience but not in early visual processing. Functional connections between these identified regions were not only associated with autistic traits but also influenced by OXTR genotype. Thus, altered patterns of neural responses to threatening faces may be a potential biomarker for autistic symptoms although modulatory influences of OXTR genotype need to be taken into account.
Subject(s)
Autistic Disorder , Receptors, Oxytocin , Adolescent , Adult , Female , Humans , Male , Young Adult , Anger , Autistic Disorder/genetics , Emotions/physiology , Genotype , Magnetic Resonance Imaging , Oxytocin , Receptors, Oxytocin/genetics , Receptors, Oxytocin/metabolismABSTRACT
Anti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.
Subject(s)
Autoantibodies , Interferon-gamma , Mycoses , Talaromyces , Th1 Cells , Humans , Talaromyces/immunology , Th1 Cells/immunology , Interferon-gamma/immunology , Autoantibodies/immunology , Autoantibodies/blood , Male , Adult , Female , China , Mycoses/immunology , Mycoses/microbiology , Middle Aged , T-Box Domain Proteins/genetics , T-Box Domain Proteins/immunology , STAT1 Transcription Factor/immunology , STAT1 Transcription Factor/geneticsABSTRACT
Constipation is a major health problem worldwide that requires effective and safe treatment options. Increasing evidence indicates that disturbances in gut microbiota may be a risk factor for constipation. Administration of lacidophilin tablets shows promising therapeutic potential in the treatment of inflammatory bowel disease owing to their immunomodulatory properties and regulation of the gut microbiota. The focus of this study was on investigating the ability of lacidophilin tablets to relieve constipation by modulating the gut microbiome. Rats with loperamide hydrochloride induced constipation were treated with lacidophilin tablets via intragastric administration for ten days. The laxative effect of lacidophilin tablets was then evaluated by investigating the regulation of intestinal microflora and the possible underlying molecular mechanism. Our results reveal that treatment with lacidophilin tablets increased the intestinal advancement rate, fecal moisture content, and colonic AQP3 protein expression. It also improved colonic microflora structure in the colonic contents of model rats mainly by increasing Akkermansia muciniphila and decreasing Clostridium_sensu_stricto_1. Transcriptome analysis indicated that treatment with lacidophilin tablets maintains the immune response in the intestine and promotes recovery of the intestinal mechanical barrier in the constipation model. Our study shows that lacidophilin tablets improve constipation, possibly by promoting Akkermansia colonization and by modulating the intestinal immune response.
Subject(s)
Gastrointestinal Microbiome , Rats , Animals , Akkermansia , Constipation/drug therapy , Intestines , LoperamideABSTRACT
BACKGROUND: Cardiovascular magnetic resonance (CMR) reference values are relied upon to accurately diagnose left ventricular (LV) and right ventricular (RV) pathologies. To date, reference values have been derived from modest sample sizes with limited patient diversity and attention to 1 but not both commonly used tracing techniques for papillary muscles and trabeculations. We sought to overcome these limitations by meta-analyzing normal reference values for CMR parameters stemming from multiple countries, vendors, analysts, and patient populations. METHODS: We comprehensively extracted published and unpublished data from studies reporting CMR parameters in healthy adults. A steady-state free-precession short-axis stack at 1.5T or 3T was used to trace either counting the papillary muscles and trabeculations in the LV volume or mass. We used a novel Bayesian hierarchical meta-analysis model to derive the pooled lower and upper reference values for each CMR parameter. Our model accounted for the expected differences between tracing techniques by including informative prior distributions from a large external data set. RESULTS: A total of 254 studies from 25 different countries were systematically reviewed, representing 12 812 healthy adults, of which 52 were meta-analyzed. For LV parameters counting papillary muscles and trabeculations in the LV volume, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 52% to 73% and 54% to 75%, LV end-diastolic volume index of 60 to 109 and 56 to 96 mL/m2, LV end-systolic volume index of 18 to 45 and 16 to 38 mL/m2, and LV mass index of 41 to 76 and 33 to 57 g/m2. For LV parameters counting papillary muscles and trabeculations in the LV mass, pooled normative reference ranges in men and women, respectively, were as follows: LV ejection fraction of 57% to 74% and 57% to 75%, LV end-diastolic volume index of 60 to 97 and 55 to 88 mL/m2, LV end-systolic volume index of 18 to 37 and 15 to 34 mL/m2, and LV mass index of 50 to 83 and 38 to 65 g/m2. For RV parameters, pooled normative reference ranges in men and women, respectively, were as follows: RV ejection fraction of 47% to 68% and 49% to 71%, RV end-diastolic volume index of 64 to 115 and 57 to 99 mL/m2, RV end-systolic volume index of 23 to 52 and 18 to 42 mL/m2, and RV mass index of 14 to 29 and 13 to 25 g/m2. CONCLUSIONS: Our Bayesian hierarchical meta-analysis provides normative reference values for CMR parameters of LV and RV size, systolic function, and mass, encompassing both tracing techniques across a diverse multinational sample of healthy men and women.
Subject(s)
Heart Ventricles , Ventricular Function, Left , Adult , Male , Humans , Female , Reference Values , Bayes Theorem , Heart Ventricles/diagnostic imaging , Stroke Volume , Papillary Muscles , Magnetic Resonance Spectroscopy , Magnetic Resonance Imaging, Cine , Reproducibility of ResultsABSTRACT
PURPOSE: To investigate the role of magnetic resonance imaging (MRI) based on radiomics using T2-weighted imaging fat suppression (T2WI-FS) and contrast enhanced T1-weighted imaging (CE-T1WI) sequences in differentiating T1-category nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPH). MATERIALS AND METHODS: This study enrolled 614 patients (training dataset: n = 390, internal validation dataset: n = 98, and external validation dataset: n = 126) of T1-category NPC and NPH. Three feature selection methods were used, including analysis of variance, recursive feature elimination, and relief. The logistic regression classifier was performed to construct the radiomics signatures of T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to differentiate T1-category NPC from NPH. The performance of the optimal radiomics signature (T2WI-FS + CE-T1WI) was compared with those of three radiologists in the internal and external validation datasets. RESULTS: Twelve, 15, and 15 radiomics features were selected from T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to develop the three radiomics signatures, respectively. The area under the curve (AUC) values for radiomics signatures of T2WI-FS + CE-T1WI and CE-T1WI were significantly higher than that of T2WI-FS (AUCs = 0.940, 0.935, and 0.905, respectively) for distinguishing T1-category NPC and NPH in the training dataset (Ps all < 0.05). In the internal and external validation datasets, the radiomics signatures based on T2WI-FS + CE-T1WI and CE-T1WI outperformed T2WI-FS with no significant difference (AUCs = 0.938, 0.925, and 0.874 for internal validation dataset and 0.932, 0.918, and 0.882 for external validation dataset; Ps > 0.05). The radiomics signature of T2WI-FS + CE-T1WI significantly performed better than three radiologists in the internal and external validation datasets. CONCLUSION: The MRI-based radiomics signature is meaningful in differentiating T1-category NPC from NPH and potentially helps clinicians select suitable therapy strategies.
Subject(s)
Hyperplasia , Magnetic Resonance Imaging , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Magnetic Resonance Imaging/methods , Male , Diagnosis, Differential , Female , Nasopharyngeal Carcinoma/diagnostic imaging , Middle Aged , Nasopharyngeal Neoplasms/diagnostic imaging , Adult , Hyperplasia/diagnostic imaging , Aged , Young Adult , Adolescent , Retrospective Studies , Contrast Media , Nasopharynx/diagnostic imaging , Reproducibility of Results , RadiomicsABSTRACT
The proper axial length of the eye is crucial for achieving emmetropia. In this study, we present a wireless battery-free eye modulation patch designed to correct high myopia and prevent relapse. The patch consists of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, µ-LEDs, a flexible circuit, and biocompatible encapsulation. The system can be wirelessly powered and controlled using external ultrasound. The electrochemical micro-actuator plays a key role in precisely shortening the axial length by driving the posterior sclera inward. This ensures accurate scene imaging on the retina for myopia eye. The drug microneedle array delivers riboflavin to the posterior sclera, and µ-LEDs' blue light induces collagen cross-linking, reinforcing sclera strength. In vivo experiments demonstrate that the patch successfully reduces the rabbit eye's axial length by ~1217 µm and increases sclera strength by 387%. The system operates effectively within the body without the need for batteries. Here, we show that the patch offers a promising avenue for clinically treating high myopia.
Subject(s)
Myopia , Animals , Rabbits , Cross-Linking Reagents/pharmacology , Disease Models, Animal , Myopia/therapy , Sclera , RiboflavinABSTRACT
Social recognition encompasses encoding social information and distinguishing unfamiliar from familiar individuals to form social relationships. Although the medial prefrontal cortex (mPFC) is known to play a role in social behavior, how identity information is processed and by which route it is communicated in the brain remains unclear. Here we report that a ventral midline thalamic area, nucleus reuniens (Re) that has reciprocal connections with the mPFC, is critical for social recognition in male mice. In vivo single-unit recordings and decoding analysis reveal that neural populations in both mPFC and Re represent different social stimuli, however, mPFC coding capacity is stronger. We demonstrate that chemogenetic inhibitions of Re impair the mPFC-Re neural synchronization and the mPFC social coding. Projection pathway-specific inhibitions by optogenetics reveal that the reciprocal connectivity between the mPFC and the Re is necessary for social recognition. These results reveal an mPFC-thalamic circuit for social information processing.
Subject(s)
Midline Thalamic Nuclei , Thalamus , Male , Mice , Animals , Recognition, Psychology , Prefrontal Cortex , Neural PathwaysABSTRACT
Maintaining or even increasing crop yields while reducing nitrous oxide (N2 O) emissions is necessary to reconcile food security and climate change, while the metric of yield-scaled N2 O emission (i.e., N2 O emissions per unit of crop yield) is at present poorly understood. Here we conducted a global meta-analysis with more than 6000 observations to explore the variation patterns and controlling factors of yield-scaled N2 O emissions for maize, wheat and rice and associated potential mitigation options. Our results showed that the average yield-scaled N2 O emissions across all available data followed the order wheat (322 g N Mg-1 , with the 95% confidence interval [CI]: 301-346) > maize (211 g N Mg-1 , CI: 198-225) > rice (153 g N Mg-1 , CI: 144-163). Yield-scaled N2 O emissions for individual crops were generally higher in tropical or subtropical zones than in temperate zones, and also showed a trend towards lower intensities from low to high latitudes. This global variation was better explained by climatic and edaphic factors than by N fertilizer management, while their combined effect predicted more than 70% of the variance. Furthermore, our analysis showed a significant decrease in yield-scaled N2 O emissions with increasing N use efficiency or in N2 O emissions for production systems with cereal yields >10 Mg ha-1 (maize), 6.6 Mg ha-1 (wheat) or 6.8 Mg ha-1 (rice), respectively. This highlights that N use efficiency indicators can be used as valuable proxies for reconciling trade-offs between crop production and N2 O mitigation. For all three major staple crops, reducing N fertilization by up to 30%, optimizing the timing and placement of fertilizer application or using enhanced-efficiency N fertilizers significantly reduced yield-scaled N2 O emissions at similar or even higher cereal yields. Our data-driven assessment provides some key guidance for developing effective and targeted mitigation and adaptation strategies for the sustainable intensification of cereal production.
Subject(s)
Agriculture , Oryza , Agriculture/methods , Triticum , Zea mays , Fertilizers , Nitrous Oxide/analysis , Crops, Agricultural , Edible Grain/chemistry , SoilABSTRACT
Increasing evidence suggests that brown adipose tissue (BAT) plays an important role in obesity and related diseases. Increasing the amount or activity of BAT could prevent obesity. Therefore, a safe and effective method of activating BAT is urgently required. Here, we evaluated the potential effects of lotus leaf extract (LLE) on BAT function. We found that LLE substantially increased UCP1 mRNA and protein levels as well as thermogenic protein expression in primary brown adipocytes. Additionally, LLE treatment reduced diet-induced obesity and improved glucose homeostasis owing to BAT activation and increased energy expenditure. We found that nuciferine, an active ingredient of LLE, could dose-dependently activate BAT in vitro and in vivo, alleviate diet-induced obesity, and improve glucose homeostasis by increasing energy expenditure. Mechanistically, we found that nuciferine induced PPARG coactivator 1 alpha (PGC1-α) expression, which is a key gene involved in mitochondrial biogenesis promoter activity, by directly binding to RXRA. Furthermore, RXRA knockdown abolished expression of the nuciferine-induced mitochondrial and thermogenesis-related gene in primary brown adipocytes. In summary, we found that LLE and nuciferine have a notable effect on BAT activation and highlight the potential applications of the main component of LLE in preventing obesity and treating metabolic disorders.
Subject(s)
Adipose Tissue, Brown , Aporphines , Humans , Adipose Tissue, Brown/metabolism , Obesity/genetics , Obesity/prevention & control , Obesity/metabolism , Aporphines/pharmacology , Energy Metabolism , Glucose/metabolismABSTRACT
Microglia actively monitor the neighboring brain microenvironments and constantly contact synapses with their unique ramified processes. In neurodegenerative diseases, including Alzheimer's disease (AD), microglia undergo morphological and functional alterations. Whether the direct manipulation of microglia can selectively or concurrently modulate synaptic function and the response to disease-associated factors remains elusive. Here, we employ optogenetic methods to stimulate microglia in vitro and in vivo. Membrane depolarization rapidly changes microglia morphology and leads to enhanced phagocytosis. We found that the optogenetic stimulation of microglia can efficiently promote ß-amyloid (Aß) clearance in the brain parenchyma, but it can also enhance synapse elimination. Importantly, the inhibition of C1q selectively prevents synapse loss induced by microglia depolarization but does not affect Aß clearance. Our data reveal independent microglia-mediated phagocytosis pathways toward Aß and synapses. Our results also shed light on a synergistic strategy of depolarizing microglia and inhibiting complement functions for the clearance of Aß while sparing synapses.
Subject(s)
Alzheimer Disease , Microglia , Humans , Microglia/metabolism , Optogenetics , Amyloid beta-Peptides/metabolism , Alzheimer Disease/metabolism , Synapses/metabolism , Complement System Proteins/metabolismABSTRACT
Time perception has been known to depend on the temporal frequency of the stimulus. Previously, the effect of temporal frequency modulation was assumed to be monotonically lengthening or shortening. However, this study shows that temporal frequency affects time perception in a non-monotonic and modality-dependent manner. Four experiments investigated the time distortion effects induced by modulation of temporal frequency across auditory and visual modalities. Critically, the temporal frequency was parametrically manipulated across four levels (steady stimulus, 10-, 20-, and 30/40-Hz intermittent auditory/visual stimulus). Experiment 1, 2, and 3 consistently showed that a 10-Hz auditory stimulus was perceived as shorter than a steady auditory stimulus. Meanwhile, as the temporal frequency increased, the perceived duration of the intermittent auditory stimulus was lengthened. A 40-Hz auditory stimulus was perceived as longer than a 10- Hz auditory stimulus, but did not differ significantly from a steady one. Experiment 4 showed that, for the visual modality, a 10-Hz visual stimulus was perceived as longer than a steady stimulus, and the perceived duration was lengthened as temporal frequency increased. This study demonstrated that within the scope of the temporal frequencies examined in this study, there were differential distortion effects observed across sensory modalities.
Subject(s)
Auditory Perception , Time Perception , Humans , Time , Visual Perception , Acoustic StimulationABSTRACT
Objective To study the traditional Chinese medicine(TCM)constitution characteristics of overweight/obese patients in Shanghai region and to investigate the correlation of TCM constitution with body composition.Methods Relevant data were collected from the patients with complete information of TCM constitution and human body composition analysis who visited the specialized outpatient clinic of acup-moxibustion catgut embedding therapy in the Department of Endocrinology,Shanghai Tenth People's Hospital from August 2020 to December 2022.The patients were divided into a normal body mass group(BMI<24 kg/m2),an overweight group(24 kg/m2≤BMI<28 kg/m2)and obesity group(BMI≥28 kg/m2),and then the distribution of TCM constitution types in the three groups of patients were analyzed.After that,the correlation between TCM constitution and body composition were explored with multiple regression analysis.Results(1)A total of 315 patients were included,of which 43 patients had normal body mass,85 patients were overweight and 187 patients were obese.(2)The TCM constitution types in descending order of the composition ratio in the normal body mass group and in the overweight group were spleen deficiency constitution,liver stagnation constitution,damp-heat constitution,yang deficiency constitution,and yin deficiency constitution,in the obese group were spleen deficiency constitution,yang deficiency constitution,damp-heat constitution,liver stagnation constitution,and yin deficiency constitution,and in the overweight/obese group were spleen deficiency constitution,damp-heat constitution,yang deficiency constitution,liver stagnation constitution,and yin deficiency constitution.No statistically significant differences of the distribution of TCM constitution types were shown between normal body bass population and overweight/obese population(P>0.05).In both normal body mass population and overweight/obese population,the single body constitution type was common,and biased constitution was rare,and there was no statistically significant difference when comparing between the two groups(P>0.05).(3)The results of multiple regression analysis showed that the basal metabolism of all patients was positively correlated with yang deficiency constitution and was negatively correlated with damp-heat constitution,and the differences were statistically significant(P<0.01).It is indicated that if the score of yang deficiency constitution rose by one point,the basal metabolism would increase by 0.54 kcal,and if the score of damp-heat constitution decreased by one point,the basal metabolism would decrease by 1.005 kcal.Conclusion In Shanghai region,obesity may be the main indication of the variation of the body constitution.In addition to spleen deficiency constitution,the proportions of yang deficiency constitution,damp-heat constitution and liver stagnation constitution are also higher in obese patients.In terms of the correlation between TCM constitution and body composition,basal metabolism is positively correlated with yang deficiency constitution and is negatively correlated with damp-heat constitution.Therefore,for the patients with yang deficiency constitution and damp-heat constitution,the influence of the basal metabolism level on the development of the disease should be taken into account.
ABSTRACT
Stereoelectroencephalography (SEEG) offers unique neural data from in-depth brain structures with fine temporal resolutions to better investigate the origin of epileptic brain activities. Although oscillatory patterns from different frequency bands and functional connectivity computed from the SEEG datasets are employed to study the epileptic zones, direct electrical stimulation-evoked electrophysiological recordings of synaptic responses, namely cortical-cortical evoked potentials (CCEPs), from the same SEEG electrodes are not explored for the localization of epileptic zones. Here we proposed a two-stream model with unsupervised learning and graph convolutional network tailored to the SEEG and CCEP datasets in individual patients to perform localization of epileptic zones. We compared our localization results with the clinically marked electrode sites determined for surgical resections. Our model had good classification capability when compared to other state-of-the-art methods. Furthermore, based on our prediction results we performed group-level brain-area mapping analysis for temporal, frontal and parietal epilepsy patients and found that epileptic and non-epileptic brain networks were distinct in patients with different types of focal epilepsy. Our unsupervised data-driven model provides personalized localization analysis for the epileptic zones. The epileptic and non-epileptic brain areas disclosed by the prediction model provide novel insights into the network-level pathological characteristics of epilepsy.
Subject(s)
Epilepsies, Partial , Epilepsy , Humans , Brain , Evoked Potentials/physiology , Brain Mapping/methods , Electroencephalography/methodsABSTRACT
BACKGROUND: Normal tension glaucoma (NTG) is considered a neurodegenerative disease with glaucomatous damage extending to diffuse brain areas. Therefore, this study aims to explore the abnormalities in the NTG structural network to help in the early diagnosis and course evaluation of NTG. METHODS: The structural networks of 46 NTG patients and 19 age- and sex-matched healthy controls were constructed using diffusion tensor imaging, followed by graph theory analysis and correlation analysis of small-world properties with glaucoma clinical indicators. In addition, the network-based statistical analysis (NBS) method was used to compare structural network connectivity differences between NTG patients and healthy controls. RESULTS: Structural brain networks in both NTG and NC groups exhibited small-world properties. However, the small-world index in the severe NTG group was reduced and correlated with a mean deviation of the visual field (MDVF) and retinal nerve fiber layer (RNFL) thickness. When compared to healthy controls, degree centrality and nodal efficiency in visual brain areas were significantly decreased, and betweenness centrality and nodal local efficiency in both visual and nonvisual brain areas were also significantly altered in NTG patients (all p < 0.05, FDR corrected). Furthermore, NTG patients exhibited increased structural connectivity in the occipitotemporal area, with the left fusiform gyrus (FFG.L) as the hub (p < 0.05). CONCLUSIONS: NTG exhibited altered global properties and local properties of visual and cognitive-emotional brain areas, with enhanced structural connections within the occipitotemporal area. Moreover, the disrupted small-world properties of white matter might be imaging biomarkers for assessing NTG progression.
ABSTRACT
BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .
Subject(s)
COVID-19 , Drugs, Chinese Herbal , Adult , Humans , Double-Blind Method , Drugs, Chinese Herbal/therapeutic use , Treatment OutcomeABSTRACT
Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.
ABSTRACT
Gastrointestinal (GI) disorders are common comorbidities in individuals with autism spectrum disorder (ASD), and abnormalities in these issues have been found to be closely related to the severity of core behavioral deficits in autism. The enteric nervous system (ENS) plays a crucial role in regulating various aspects of gut functions, including gastrointestinal motility. Dysfunctional wiring in the ENS not only results in various gastrointestinal issues, but also correlates with an increasing number of central nervous system (CNS) disorders, such as ASD. However, it remains unclear whether the gastrointestinal dysfunctions are a consequence of ASD or if they directly contribute to its pathogenesis. This review focuses on the deficits in the ENS associated with ASD, and highlights several high-risk genes for ASD, which are expressed widely in the gut and implicated in gastrointestinal dysfunction among both animal models and human patients with ASD. Furthermore, we provide a brief overview of environmental factors associated with gastrointestinal tract in individuals with autism. This could offer fresh perspectives on our understanding of ASD.