Background: One in four individuals with Parkinson's disease (PD) experience cognitive impairment (CI). However, few practical models integrating clinical and neuroimaging biomarkers have been developed to address CI in PD. This study aimed to evaluate the correlation between circulating neuron-specific enolase (NSE) levels, substantia nigra hyperechogenicity (SNH), and cognitive function in PD and to develop a nomogram based on clinical and neuroimaging biomarkers for predicting CI in patients with PD. Methods: A total of 385 patients with PD who underwent transcranial sonography (TCS) from January 2021 to December 2022 at Beijing Tiantan Hospital, Capital Medical University, were recruited as the training cohort. For validation, 165 patients with PD treated from January 2023 to December 2023 were enrolled. Data for SNH, plasma NSE, and other clinical measures were collected, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Logistic regression analysis was employed to select potential risk factors and establish a nomogram. The receiver operating characteristic curve and calibration curve were generated to evaluate the performance of the nomogram. Results: Patients with PD exhibiting CI displayed advanced age, elevated Unified PD Rating Scale-III (UPDRS-III) score, an increased percentage of SNH, higher levels of plasma NSE and homocysteine (Hcy), a larger SNH area, and lower education levels compared to PD patients without CI. Gender [odds ratio (OR) =0.561, 95% confidence interval (CI): 0.330-0.954, P=0.03], age (OR =1.039; 95% CI: 1.011-1.066; P=0.005), education level (OR =0.892; 95% CI: 0.842-0.954; P<0.001), UPDRS-III scores (OR =1.026; 95% CI: 1.009-1.043; P=0.003), plasma NSE concentration (OR =1.562; 95% CI: 1.374-1.776; P<0.001), and SNH (OR =0.545; 95% CI: 0.330-0.902; P=0.02) were independent predictors of CI in patients with PD. A nomogram developed using these six factors yielded a moderate discrimination performance with an area under the curve (AUC) of 0.823 (95% CI 0.781-0.864; P<0.001). The calibration curve demonstrated acceptable agreement between predicted outcomes and actual values. Validation further confirmed the reliability of the nomogram, with an AUC of 0.864 (95% CI: 0.805-0.922; P<0.001). Conclusions: The level of NSE in plasma and the SNH assessed by TCS are associated with CI in patients with PD. The proposed nomogram has the potential to facilitate the detection of cognitive decline in individuals with PD.
Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.
Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (Tcrónico) permaneció constante, mientras que la tolerancia al calor agudo (Tagudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.
The deterioration of anhydrite rock exposed to a freeze-thaw environment is a complex process. Therefore, this paper systematically investigated the physical and mechanical evolutions of freeze-thawed anhydrite rock through a series of multi-scale laboratory tests. Meanwhile, the correlation between pore structure and macroscopic mechanical parameters was discussed, and the deterioration mechanisms of anhydrite rock under freeze-thaw cycles were revealed. The results show that with the increase in freeze-thaw processes, the mechanical strength, elastic modulus, cohesion, proportions of micropores (r ≤ 0.1 µm), and PT-Ipore throat (0-0.1 µm) decrease exponentially. In comparison, the mass variation, proportions of mesopores (0.1 µm < r < 1 µm), macropores (r ≥ 1 µm), and PT-II pore throat (0.1-4 µm) increase exponentially. After 120 cycles, the mean porosity increases by 66.27%, and there is a significant honeycomb and pitted surface phenomenon. Meanwhile, as the freeze-thaw cycles increase, the frost resistance coefficient decreases, while the damage variable increases. The correlation analysis between pore structure and macroscopic mechanical parameters shows that macropores play the most significant role in the mechanical characteristic deterioration of freeze-thawed anhydrite rock. Finally, it is revealed that the water-rock expansion and water dissolution effects play a crucial role in the multi-scale damage of anhydrite rock under the freeze-thaw environment.
OBJECTIVE: This study aimed to examine the clinical and multimodal ultrasonic characteristics differences between carotid web (CW) and CW with plaque as well as the potential risk factors for stroke caused by CW. METHODS: We retrospectively enrolled patients diagnosed with CW by CTA or high-resolution MRI (HRMRI) and simultaneously underwent contrast enhanced ultrasound (CEUS) and superb microvascular imaging examinations from January 2015 to October 2022. The CW angle was measured using computer-aided software. The variations between CW and CW with plaque were evaluated, and univariable and multivariable logistic regressions were utilized to identify possible risk predictors for stroke caused by CW. RESULTS: Two hundred ninety-nine patients with an average age of 60.85 (± 8.77) years were included. Sex, age, history of smoking, alcohol, hypertension, diabetes mellitus, homocysteine level, and treatment, as well as web length and thickness, luminal stenosis, location wall, number, CW angle, and CEUS enhancement, were quite different among CW and CW with plaque patients (p < 0.05). The logistic regression analysis showed that web length was an independent predictor of luminal stenosis in CW patients. For patients with CW and plaque, plaque and web thickness, as well as plaque enhancement, were associated with stenosis. Furthermore, luminal stenosis and plaque length were risk factors for symptoms. CONCLUSION: The multimodal ultrasonic and clinical manifestations of CW and CW with plaque are quite different. Web length is an independent risk factor for carotid artery stenosis in CW patients, whereas luminal stenosis and plaque length were risk factors for symptoms in CW with plaque patients. CRITICAL RELEVANCE STATEMENT: Exploring the similarities and differences between the carotid web and the carotid web with plaque, based on the stereo-geometric spatial position relationship and hemodynamic changes, may provide further insights into the underlying mechanisms of stroke occurrence caused by the carotid web. KEY POINTS: 1. Multimodal ultrasonic and clinical manifestations of carotid web and carotid web with plaque are substantially different. 2. A thin triangular endoluminal defect is identified as a typical feature of the web on superb microvascular imaging, and two kinds of typical ultrasonic features of CW with plaque are also identified. 3. Web length is an independent risk factor for carotid stenosis in carotid web patients, whereas luminal stenosis and plaque length are risk factors for symptoms in patients with CW and plaque.
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age, which often leads to female infertility. Chronic inflammation is a significant factor in the development of PCOS. Our study aimed to explore the impact of mesencephalic astrocyte-derived neurotrophic factor (MANF), a scientifically validated anti-inflammatory factor, on 99 diagnosed PCOS patients. We also investigated its effects on PCOS mice induced with dehydroepiandrosterone (DHEA) and KGN cells induced with dihydrotestosterone (DHT). Our findings revealed a decrease in serum MANF levels in PCOS patients, which were negatively associated with serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. The administration of recombinant human MANF (rhMANF) in PCOS mice demonstrated a decrease in pro-inflammatory cytokines and monocytes/macrophages in both peripheral blood and ovarian tissues. Furthermore, the inclusion of rhMANF notably ameliorated DHEA-induced ovarian dysfunction and fibrosis by negatively regulating the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB)-NLR family, pyrin domain containing protein 3 (NLRP3) pathway. Additionally, in vitro experiments showed that the up-regulation of MANF offset DHT-induced inhibition of viability and apoptosis in KGN cells. Collectively, this study highlights the anti-inflammatory properties of MANF in PCOS and suggests its potential as a therapeutic approach for the management of PCOS.
Polycystic Ovary Syndrome , Female , Humans , Mice , Animals , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/complications , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Toll-Like Receptor 4 , Astrocytes/metabolism , Anti-Inflammatory Agents/therapeutic use , Nerve Growth Factors , Dehydroepiandrosterone/pharmacology , Dehydroepiandrosterone/therapeutic use
Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.
Biomarkers , Ferroptosis , Nephrolithiasis , Ferroptosis/drug effects , Animals , Nephrolithiasis/metabolism , Nephrolithiasis/genetics , Nephrolithiasis/pathology , Rats , Biomarkers/metabolism , Humans , Male , Calcium Oxalate/metabolism , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Kidney Calculi/metabolism , Kidney Calculi/genetics , Kidney Calculi/pathology , Cyclohexylamines/pharmacology , Phenylenediamines/pharmacology , Disease Models, Animal , Rats, Sprague-Dawley , Cell Line
Corneal endothelial keratoplasty has been the primary treatment method of endothelial decompensation, but it is often limited in clinical practice due to global shortage of donor cornea. Here, we explored using an ultra-thin allogeneic cornea-derived matrix (uACM) films as a substrate for constructing bioengineered corneal endothelial grafts. We evaluated the films' optical, mechanical, and structural properties, and measured the composition of the extracellular matrix. The uACM was an ultrathin and curved cornea-shaped film with favorable optical and mechanical properties. The fabrication process efficiently preserved corneal extracellular matrix composition and significantly decreased cellular components. Moreover, human corneal endothelial cells and rabbit corneal endothelial cells (RCECs) can adhere and grow on the uACM films with a positive expression of the corneal endothelial functional markers Na+/K+-ATPase and ZO-1. The successful transplantation of uACM with RCECs grafts into the rabbit model of endothelial dysfunction via Descemet membrane endothelial keratoplasty resulted in prompt restoration of corneal transparency and thickness. During the four-week follow-up period, the uACM with RCECs implanted eyes exhibited comparable corneal transparency, central corneal thickness, and endothelial cell count to that of the healthy rabbit. Histologic examination revealed that the grafts were successfully attached and integrated onto the posterior surface of the corneal stroma. The uACM achieved biomimetic reconstruction in terms of both composition and structure, and can be used to construct the bioengineered corneal endothelial grafts. These results indicate that constructing bioengineered corneal endothelial grafts from discarded human corneal tissues may pave the way for generating high-quality corneal endothelial grafts for transplantation.
Transgranular brittle fracture is the dominant failure mode of brittle materials, including ceramics and ceramic matrix composites. However, strengthening these materials without sacrificing their toughness has been a big challenge. In this study, an innovative approach is proposed to achieve coordinated strengthening and toughening of ceramics-based composites by introducing specific ductile coherent nanoparticles into ceramic grains. As an example, the WC-Co cemented tungsten carbides were used to demonstrate how this brittle material can achieve ultrahigh strength without losing toughness by seeding metallic nanoparticles inside WC grains. The mechanisms for inducing the formation and modulating the amount, size, and distribution of such nanophase within the ceramic grains were disclosed. The fraction of transgranular ruptures of the brittle ceramic phase was reduced significantly due to the presence of the ductile coherent in-grain nanoparticles. Both the strength and strain limit of the cemented carbides were remarkably increased compared to their counterparts reported in the literature. The coordinated strengthening and toughening strategy proposed in this work is applicable to a broad range of ceramics and ceramic matrix composites to obtain superior comprehensive mechanical properties.
Simultaneous improvement of strength and conductivity is urgently demanded but challenging for bimetallic materials. Here we show by creating a self-assembled lamellar (SAL) architecture in W-Cu system, enhancement in strength and electrical conductivity is able to be achieved at the same time. The SAL architecture features alternately stacked Cu layers and W lamellae containing high-density dislocations. This unique layout not only enables predominant stress partitioning in the W phase, but also promotes hetero-deformation induced strengthening. In addition, the SAL architecture possesses strong crack-buffering effect and damage tolerance. Meanwhile, it provides continuous conducting channels for electrons and reduces interface scattering. As a result, a yield strength that doubles the value of the counterpart, an increased electrical conductivity, and a large plasticity were achieved simultaneously in the SAL W-Cu composite. This study proposes a flexible strategy of architecture design and an effective method for manufacturing bimetallic composites with excellent integrated properties.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell cell invasion assay data shown in Fig. 2C on p. 7248 and Fig. 3G on p. 7249 were strikingly similar to data in different form in other articles written by different authors at different research institutes, which had either already been published (some of which have now been retracted), or had been submitted for publication at around the same time. Owing to the fact that certain of the data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 72457252, 2017; DOI: 10.3892/mmr.2017.7531].
AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.
Background: Although imaging techniques provide information about the morphology and stability of carotid plaque, they are operator dependent and may miss certain subtleties. A variety of radiomics models for carotid plaque have recently been proposed for identifying vulnerable plaques and predicting cardiovascular and cerebrovascular diseases. The purpose of this review was to assess the risk of bias, reporting, and methodological quality of radiomics models for carotid atherosclerosis plaques. Methods: A systematic search was carried out to identify available literature published in PubMed, Web of Science, and the Cochrane Library up to March 2023. Studies that developed and/or validated machine learning models based on radiomics data to identify and/or predict unfavorable cerebral and cardiovascular events in carotid plaque were included. The basic information of each piece of included literature was identified, and the reporting quality, risk of bias, and radiomics methodology quality were assessed according the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) checklist, the Prediction Model Risk of Bias Assessment Tool (PROBAST), and the radiomics quality score (RQS), respectively. Results: A total of 2,738 patients from 19 studies were included. The mean overall TRIPOD adherence rate was 66.1% (standard deviation 12.8%), with a range of 45-87%. All studies had a high overall risk of bias, with the analysis domain being the most common source of bias. The mean RQS was 9.89 (standard deviation 5.70), accounting for 27.4% of the possible maximum value of 36. The mean area under the curve for diagnostic or predictive properties of these included radiomics models was 0.876±0.09, with a range of 0.741-0.989. Conclusions: Radiomics models may have value in the assessment of carotid plaque, the overall scientific validity and reporting quality of current carotid plaque radiomics reports are still lacking, and many barriers must be overcome before these models can be applied in clinical practice.
BACKGROUND: Iron overload plays an important role in hydrocephalus development following intraventricular hemorrhage (IVH). Aquaporin 4 (AQP4) participates in the balance of cerebrospinal fluid secretion and absorption. The current study investigated the role of AQP4 in the formation of hydrocephalus caused by iron overload after IVH. METHODS: There were three parts to this study. First, Sprague-Dawley rats received an intraventricular injection of 100 µl autologous blood or saline control. Second, rats had IVH and were treated with deferoxamine (DFX), an iron chelator, or vehicle. Third, rats had IVH and were treated with 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020), a specific AQP4 inhibitor, or vehicle. Rats underwent T2-weighted and T2* gradient-echo magnetic resonance imaging to assess lateral ventricular volume and intraventricular iron deposition at 7, 14, and 28 days after intraventricular injection and were then euthanized. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence analyses were conducted on the rat brains to evaluate the expression of AQP4 at different time points. Hematoxylin and eosin-stained brain sections were obtained to assess the ventricular wall damage on day 28. RESULTS: Intraventricular injection of autologous blood caused a significant ventricular dilatation, iron deposition, and ventricular wall damage. There was increased AQP4 mRNA and protein expression in the periventricular tissue in IVH rats through day 7 to day 28. The DFX treatment group had a lower lateral ventricular volume and less intraventricular iron deposition and ventricular wall damage than the vehicle-treated group after IVH. The expression of AQP4 protein in periventricular tissue was also inhibited by DFX on days 14 and 28 after IVH. The use of TGN-020 attenuated hydrocephalus development after IVH and inhibited the expression of AQP4 protein in the periventricular tissue between day 14 and day 28 without a significant effect on intraventricular iron deposition or ventricular wall damage. CONCLUSIONS: AQP4 located in the periventricular area mediated the effect of iron overload on hydrocephalus after IVH.
Hydrocephalus , Iron Overload , Niacinamide , Thiadiazoles , Animals , Rats , Aquaporin 4/therapeutic use , Cerebral Hemorrhage/drug therapy , Hydrocephalus/etiology , Injections, Intraventricular , Iron/metabolism , Iron Overload/complications , Niacinamide/analogs & derivatives , Rats, Sprague-Dawley
Acute liver injury (ALI) is a significant causative factor for multiple hepatic diseases. The excessive inflammatory response triggers proinflammatory immune cells recruitment, infiltration and differentiation, further contributing to inflammatory injuries in liver. As a proinflammatory factor, circulating Peroxiredoxin 1 (Prdx1) is elevated in ALI patients and mice. In this study, through carbon tetrachloride (CCl4) and cecal puncture and ligation (CLP)-induced liver injury mice model, we found hepatocytes-derived Prdx1 expression was increased in ALI. After AAV8-Prdx1-mediated Prdx1 knockdown, CCl4 and CLP-induced ALI was alleviated, along with the reduced proinflammatory cytokines, suppressed myeloid cells recruitment, decreased proportions of hepatic macrophages and neutrophils, restrained proinflammatory macrophage differentiation and infiltration. Mechanistically, hepatocyte-derived Prdx1 regulated macrophages through paracrine activation of the TLR4 signal. Our data support the immune and inflammatory regulatory role of Prdx1 in ALI pathological process to suggest its potential therapeutic application and clinical value.
Peroxiredoxins , Toll-Like Receptor 4 , Animals , Humans , Mice , Hepatocytes/metabolism , Liver/pathology , Macrophages/metabolism , Peroxiredoxins/genetics , Peroxiredoxins/metabolism , Phenotype , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism
BACKGROUND: Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue. METHODS: This is a nested case-control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis. RESULTS: A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87-43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10. CONCLUSION: Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression.
COVID-19 , Cerebrovascular Disorders , Humans , Male , Female , Depression/etiology , Patient Discharge , COVID-19/epidemiology , Case-Control Studies , Post-Acute COVID-19 Syndrome , Fatigue/epidemiology , Fatigue/etiology , Anxiety/etiology , Survivors
Disrupted protein phosphorylation due to genetic variation is a widespread phenomenon that triggers oncogenic transformation of healthy cells. However, few relevant phosphorylation disruption events have been verified due to limited biological experimental methods. Because of the lack of reliable benchmark datasets, current bioinformatics methods primarily use sequence-based traits to study variant impact on phosphorylation (VIP). Here, we increased the number of experimentally supported VIP events from less than 30 to 740 by manually curating and reanalyzing multi-omics data from 916 patients provided by the Clinical Proteomic Tumor Analysis Consortium. To predict VIP events in cancer cells, we developed VIPpred, a machine learning method characterized by multidimensional features that exhibits robust performance across different cancer types. Our method provided a pan-cancer landscape of VIP events, which are enriched in cancer-related pathways and cancer driver genes. We found that variant-induced increases in phosphorylation events tend to inhibit the protein degradation of oncogenes and promote tumor suppressor protein degradation. Our work provides new insights into phosphorylation-related cancer biology as well as novel avenues for precision therapy.
Neoplasms , Proteomics , Humans , Phosphorylation , Oncogenes , Carcinogenesis/genetics , Neoplasms/metabolism
Introduction: Resveratrol is an immune modulator that can reduce M1 macrophage polarization in vitro. Reducing macrophage recruitment and M1 polarization can prevent corneal allograft rejection (CGR). In this study, rat corneal allograft rejection models were established to explore the effects of resveratrol on CGR and macrophages and the underlying mechanisms after corneal transplantation. Methods: Corneal allograft models were established, and 100 mg/kg resveratrol was injected intraperitoneally. The corneal allografts were assessed clinically using the Holland rejection scoring system, anterior segment photography, and anterior segment optical coherence tomography. Corneal macrophages, pro-inflammatory cytokines, and corneal lymphatic vessels were detected using hematoxylin and eosin staining, immunofluorescence staining, and real-time quantitative polymerase chain reaction (qRT-PCR). Dendritic cells (DCs) in cervical lymph nodes were explored using flow cytometry. RNA sequencing experiments were conducted to identify the mechanisms through which resveratrol affected CGR. The results were verified using Simple Western analysis. Pro-inflammatory cytokines by macrophages in vitro were measured using qRT-PCR and enzyme-linked immunosorbent assays. Results: Resveratrol significantly prolonged the survival of corneal grafts and reduced graft edema and central corneal thickness. Corneal macrophage recruitment and M1 macrophage polarization decreased significantly after corneal transplantation in the resveratrol group. Resveratrol also reduced pro-inflammatory cytokines in corneal grafts and suppressed the early generation of cornea lymphatic vessels and the recruitment of cornea inflammatory cells 14 days after surgery. Resveratrol decreased the proportion of DCs in ipsilateral cervical lymph nodes. The effect of resveratrol on CGR was related to the phosphatidylinositol 3-kinase/protein kinase-B (PI3K/Akt) pathway. Resveratrol reduced the secretion of pro-inflammatory cytokines by M1 macrophages in vitro. Conclusion: Our findings suggest that resveratrol can reduce corneal macrophage recruitment and M1 macrophage polarization after corneal transplantation in rats and prevent CGR. The PI3K/Akt pathway may be an important mechanism that warrants further research.
BACKGROUND: Pre-traumatic frailty in geriatric trauma patients has caught attention from emergency medical workers and the assessment of it thus become one of the important aspects of risk management. Several tools are available to identify frailty, but limited tools have been validated for geriatric trauma patients in China to assess pre-traumatic frailty.The aim of this study is to translate the Trauma-Specific Frailty Index(TSFI) into Chinese, and to evaluate the reliability and validity of the translated version in geriatric trauma patients. METHODS: A cross-sectional study was conducted. The TSFI was translated with using the Brislin model, that included forward and backward translation. A total of 184 geriatric trauma patients were recruited by a convenience sampling between October and December 2020 in Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan. Using reliability or internal consistency tests assessed with Cronbach's alpha coefficient, split-half reliability and test-retest reliability. Content validity and construct validity analysis were both performed. Sensitivity, specificity and maximum Youden index(YI) were used to determine the optimal cut-off value. The screening performance was examined by Kappa value. RESULTS: The total study population included 184 subjects, of which 8 participants were excluded, resulting in a study sample size of 176 elderly trauma patients (the completion rate was 95.7%). The Chinese version of Trauma-Specific Frailty Index(C-TSFI) have 15 items with 5 dimensions. Cronbach's alpha coefficient of the C-TSFI was 0.861, Cronbach's alpha coefficient of dimensions ranged from 0.837 to 0.875, the split-half reliability of the C-TSFI were 0.894 and 0.880 respectively, test-retest reliability ranged from 0.692 to 0.862. The correlation coefficient between items and the C-TSFI ranged from 0.439 to 0.761. The content validity index for items (I-CVI) of the C-TSFI scale was 0.86~1.00, and the scale of content validity index (S-CVI) was 0.93. The area under curve (AUC) of the C-TSFI was 0.932 (95%CI 0.904-0.96, P < 0.05), the maximum YI was 0.725, the sensitivity was 80.2%, the specificity was 92.3%, and the critical value was 0.31. Kappa value was 0.682 (P < 0.05). CONCLUSIONS: The Chinese version of TSFI could be used as a general assessment tool in geriatric trauma patients, and both its reliability and validity have been demonstrated.
Frailty , Humans , Aged , Frailty/diagnosis , Reproducibility of Results , Cross-Sectional Studies , Patients , Hospitals , China/epidemiology , Psychometrics/methods , Surveys and Questionnaires
