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BACKGROUND: Neuroinflammation is the pathological basis of many neurological diseases, including neurodegenerative diseases and stroke. Hua-Feng-Dan (HFD) is a well-established traditional Chinese medicine that has been used for centuries to treat stroke and various other brain-related ailments. OBJECTIVE: Our study aims to elucidate the molecular mechanism by which HFD mitigates neuroinflammation by combining network pharmacology and in vitro experiments. METHODS: TCMSP and SymMap databases were used to extract active compounds and their related targets. The neuroinflammation-related targets were obtained from the GeneCards database. The common targets of HFD and neuroinflammation were used to construct a protein-protein interaction (PPI) network. MCODE plug-in was used to find the hub module genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to dissect the hub module genes. The lipopolysaccharide (LPS)-induced BV2 microglial neuroinflammation model was utilized to assess the therapeutic effects of HFD on neuroin- flammation. Western blotting analysis was performed to examine the core target proteins in the TLR4/My- D88/NF-κB signaling pathway, potentially implicated in HFD's therapeutic effects on neuroinflammation. Hoechst 33342 staining and JC-1 staining were employed to evaluate neuronal apoptosis. RESULTS: Through network pharmacology, 73 active compounds were identified, with quercetin, beta-sitos- terol, luteolin, and (-)-Epigallocatechin-3-Gallate recognized as important compounds. Meanwhile, 115 com- mon targets of HFD and neuroinflammation were identified, and 61 targets were selected as the hub targets uti- lizing the MCODE algorithm. The results of in vitro experiments demonstrated that HFD significantly inhibit- ed microglial-mediated neuronal inflammation induced by LPS. Integrating the predictions from network phar- macology with the in vitro experiment results, it was determined that the mechanism of HFD in mitigating neu- roinflammation is closely related to the TLR4/MyD88/NF-κB pathway. Furthermore, HFD demonstrated the capacity to shield neurons from apoptosis by curbing the secretion of pro-inflammatory factors subsequent to microglial activation. CONCLUSION: The findings demonstrated that HFD had an inhibitory effect on LPS-induced neuroinflammation in microglia and elucidated its underlying mechanism. These findings will offer a theoretical foundation for the clinical utilization of HFD in treating neurodegenerative diseases associated with neuroinflammation.
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Objectives: The impact of climate change, especially extreme temperatures, on health outcomes has become a global public health concern. Most previous studies focused on the impact of disease incidence or mortality, whereas much less has been done on road traffic injuries (RTIs). This study aimed to explore the effects of ambient temperature, particularly extreme temperature, on road traffic deaths in Jinan city. Methods: Daily data on road traffic deaths and meteorological factors were collected among all residents in Jinan city during 2011-2020. We used a time-stratified case-crossover design with distributed lag nonlinear model to evaluate the association between daily mean temperature, especially extreme temperature and road traffic deaths, and its variation in different subgroups of transportation mode, adjusting for meteorological confounders. Results: A total of 9,794 road traffic deaths were collected in our study. The results showed that extreme temperatures were associated with increased risks of deaths from road traffic injuries and four main subtypes of transportation mode, including walking, Bicycle, Motorcycle and Motor vehicle (except motorcycles), with obviously lag effects. Meanwhile, the negative effects of extreme high temperatures were significantly higher than those of extreme low temperatures. Under low-temperature exposure, the highest cumulative lag effect of 1.355 (95% CI, 1.054, 1.742) for pedal cyclists when cumulated over lag 0 to 6 day, and those for pedestrians, motorcycles and motor vehicle occupants all persisted until 14 days, with ORs of 1.227 (95% CI, 1.102, 1.367), 1.453 (95% CI, 1.214, 1.740) and 1.202 (95% CI, 1.005, 1.438), respectively. Under high-temperature exposure, the highest cumulative lag effect of 3.106 (95% CI, 1.646, 5.861) for motorcycle occupants when cumulated over lag 0 to 12 day, and those for pedestrian, pedal cyclists, and motor vehicle accidents all peaked when persisted until 14 days, with OR values of 1.638 (95% CI, 1.281, 2.094), 2.603 (95% CI, 1.695, 3.997) and 1.603 (95% CI, 1.066, 2.411), respectively. Conclusion: This study provides evidence that ambient temperature is significantly associated with the risk of road traffic injuries accompanied by obvious lag effect, and the associations differ by the mode of transportation. Our findings help to promote a more comprehensive understanding of the relationship between temperature and road traffic injuries, which can be used to establish appropriate public health policies and targeted interventions.
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Accidentes de Tránsito , Estudios Cruzados , Dinámicas no Lineales , Temperatura , Humanos , Accidentes de Tránsito/estadística & datos numéricos , China/epidemiología , Masculino , Femenino , Adulto , Heridas y Lesiones/epidemiología , Heridas y Lesiones/mortalidad , Ciudades , Persona de Mediana Edad , AdolescenteRESUMEN
Some Brucella spp. are important pathogens. According to the latest prokaryotic taxonomy, the Brucella genus consists of facultative intracellular parasitic Brucella species and extracellular opportunistic or environmental Brucella species. Intracellular Brucella species include classical and nonclassical types, with different species generally exhibiting host preferences. Some classical intracellular Brucella species can cause zoonotic brucellosis, including B. melitensis, B. abortus, B. suis, and B. canis. Extracellular Brucella species comprise opportunistic or environmental species which belonged formerly to the genus Ochrobactrum and thus nowadays renamed as for example Brucella intermedia or Brucella anthropi, which are the most frequent opportunistic human pathogens within the recently expanded genus Brucella. The cause of the diverse phenotypic characteristics of different Brucella species is still unclear. To further investigate the genetic evolutionary characteristics of the Brucella genus and elucidate the relationship between its genomic composition and prediction of phenotypic traits, we collected the genomic data of Brucella from the NCBI Genome database and conducted a comparative genomics study. We found that classical and nonclassical intracellular Brucella species and extracellular Brucella species exhibited differences in phylogenetic relationships, horizontal gene transfer and distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes, showing the close relationship between the genetic variations and prediction of phenotypic traits of different Brucella species. Furthermore, we found significant differences in horizontal gene transfer and the distribution patterns of mobile genetic elements, virulence factor genes, and antibiotic resistance genes between the two chromosomes of Brucella, indicating that the two chromosomes had distinct dynamics and plasticity and played different roles in the survival and evolution of Brucella. These findings provide new directions for exploring the genetic evolutionary characteristics of the Brucella genus and could offer new clues to elucidate the factors influencing the phenotypic diversity of the Brucella genus.
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Central fatigue is a common pathological state characterized by psychological loss of drive, lack of appetite, drowsiness, and decreased psychic alertness. The mechanism underlying central fatigue is still unclear, and there is no widely accepted successful animal model that fully represents human characteristics. We aimed to construct a more clinically relevant and comprehensive animal model of central fatigue. In this study, we utilized the Modified Multiple Platform Method (MMPM) combined with alternate-day fasting (ADF) to create the animal model. The model group rats are placed on a stationary water environment platform for sleep deprivation at a fixed time each day, and they were subjected to ADF treatment. On non-fasting days, the rats were allowed unrestricted access to food. This process was sustained over a period of 21 days. We evaluated the model using behavioral assessments such as open field test, elevated plus maze test, tail suspension test, Morris water maze test, grip strength test, and forced swimming test, as well as serum biochemical laboratory indices. Additionally, we conducted pathological observations of the hippocampus and quadriceps muscle tissues, transmission electron microscope observation of mitochondrial ultrastructure, and assessment of mitochondrial energy metabolism and oxidative stress-related markers. The results revealed that the model rats displayed emotional anomalies resembling symptoms of depression and anxiety, decreased exploratory behavior, decline in learning and memory function, and signs of skeletal muscle fatigue, successfully replicating human features of negative emotions, cognitive decline, and physical fatigue. Pathological damage and mitochondrial ultrastructural alterations were observed in the hippocampus and quadriceps muscle tissues, accompanied by abnormal mitochondrial energy metabolism and oxidative stress in the form of decreased ATP and increased ROS levels. In conclusion, our ADF+MMPM model comprehensively replicated the features of human central fatigue and is a promising platform for preclinical research. Furthermore, the pivotal role of mitochondrial energy metabolism and oxidative stress damage in the occurrence of central fatigue in the hippocampus and skeletal muscle tissues was corroborated.
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Modelos Animales de Enfermedad , Animales , Ratas , Masculino , Ratas Sprague-Dawley , Estrés Oxidativo/fisiología , Hipocampo/metabolismo , Humanos , Fatiga/fisiopatología , Privación de Sueño , Mitocondrias/metabolismo , Síndrome de Fatiga Crónica/fisiopatología , Ayuno/fisiología , Músculo Esquelético , Aprendizaje por Laberinto/fisiologíaRESUMEN
Two vaccines ACAM 2000 and JYNNEOS have obtained approval from the Food and Drug Administration as preventive measures against monkeypox, contributing significantly to the management of the monkeypox epidemic. Nonetheless, research has demonstrated that smallpox vaccination offers approximately 88.8% protection against monkeypox, while immunization with these vaccines generates relatively low levels of neutralizing antibodies. In this work, we performed a comprehensive comparison of antigens between the 2022-2023 monkeypox strains and the smallpox vaccine strains. Our analysis has revealed considerable amino acid changes in all 27 antigens, including core and envelope proteins. Amino acid substitutions within B cell epitopes were observed in 26 of these antigens, with at least half of the antigen substitutions occurring within B cell epitopes in 20 out of the 26 antigens analyzed. These findings may raise potential concerns regarding the efficacy of these vaccines.
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Mpox , Vacuna contra Viruela , Viruela , Humanos , Mpox/epidemiología , Mpox/prevención & control , Monkeypox virus , Viruela/prevención & control , Epítopos de Linfocito B , VacunaciónRESUMEN
The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.
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Many clinical studies have demonstrated a correlation between psoriasis vulgaris and dementia, yet this correlation remains controversial. Our study employed the Mendelian randomization (MR) method to investigate the causal relationship between psoriasis vulgaris and dementia. Data were obtained from the summary statistics of the genome-wide association studies from IEU-OpenGWAS project database. In univariate Mendelian randomization (UVMR) analysis, psoriasis vulgaris was used as exposure. Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD) and frontotemporal dementia (FTD) served as the outcomes. In multivariate Mendelian randomization (MVMR) analysis, VaD served as the outcome. The first MVMR analysis used psoriasis vulgaris, mean platelet volume (MPV), platelet distribution width (PDW) and platelet count (PLT) as exposures. The second MVMR analysis used psoriasis vulgaris, vitamin D level and 25 hydroxyvitamin D level as exposures. The main analysis employed the inverse variance weighted method, and the outcomes were evaluated by odds ratio (OR) and 95% confidence interval (95% CI). In UVMR analysis, the results depicted that psoriasis vulgaris was associated with VaD (OR: 0.903, 95% CI: 0.818-0.996, p = 0.041). The results revealed insignificant associations between psoriasis vulgaris and other dementia types. After adjusting the effects of MPV, PDW and PLT in MVMR analysis, the association between psoriasis vulgaris and VaD was no longer significant (p = 0.164). Similarly, after adjusting the effects of vitamin D level and 25 hydroxyvitamin D level in MVMR analysis, the association between psoriasis vulgaris and VaD was also no longer significant (p = 0.533). Our study suggests that psoriasis vulgaris may potentially decrease VaD incidence. However, the causal association between psoriasis vulgaris and VaD may be impeded by platelet-related indices, vitamin D level and 25 hydroxyvitamin D level.
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Demencia , Psoriasis , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Psoriasis/complicaciones , Psoriasis/genética , Calcifediol , Vitamina D , Demencia/etiología , Demencia/genéticaRESUMEN
OBJECTIVE: The purpose of this study was to identify significant prognostic factors associated with facial paralysis after vestibular schwannoma (VS) surgery and develop a novel nomogram for predicting facial nerve (FN) outcomes. METHODS: Retrospective data were retrieved from 355 patients who underwent microsurgery via the retrosigmoid approach for VS between December 2017 and December 2022. Univariate and multivariate logistic regression analysis were used to construct a radiographic features-based nomogram to predict the risk of facial paralysis after surgery. RESULTS: Following a thorough screening process, a total of 185 participants were included. The univariate and multivariate logistic regression analysis revealed that tumor size (p = 0.005), fundal fluid cap (FFC) sign (p = 0.014), cerebrospinal fluid cleft (CSFC) sign (p < 0.001), and expansion of affected side of internal auditory canal (IAC) (p = 0.033) were independent factors. A nomogram model was constructed based on these indicators. When applied to the validation cohort, the nomogram demonstrated good discrimination and favorable calibration. Then we generated a web-based calculator to facilitate clinical application. CONCLUSION: Tumor size, FFC and CSFC sign, and the expansion of the IAC, serve as good predictors of postoperative FN outcomes. Based on these factors, the nomogram model demonstrates good predictive performance.
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Parálisis Facial , Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/cirugía , Nervio Facial/diagnóstico por imagen , Nervio Facial/cirugía , Estudios Retrospectivos , Parálisis Facial/diagnóstico por imagen , Parálisis Facial/etiología , NomogramasRESUMEN
We report 26 cases of eye injuries resulting from cobra venom sprayed by Naja atra. This accounts for 14.5% of patients (26/173) treated for cobra injuries who presented to the emergency department of a snakebite treatment center in Guangzhou, South China. Pain, blurred vision, lacrimation, photophobia, and foreign body sensation were the most common symptoms, found in 24 patients. Ophthalmic examination revealed eyelid swelling and conjunctival congestion. Eye slit lamp examination showed obvious punctate corneal epithelial defects in four patients. Five patients received an intravenous infusion of antivenom. All patients' eyes were rinsed completely with normal saline after their arrival at the hospital. Prophylactic topical antibiotics were given to all patients. All eyes were cured without long-term sequelae.
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Endoftalmitis , Mordeduras de Serpientes , Animales , Humanos , Elapidae , Venenos Elapídicos , Venenos de Serpiente , Endoftalmitis/etiología , Antivenenos/uso terapéutico , Mordeduras de Serpientes/complicaciones , Mordeduras de Serpientes/tratamiento farmacológicoRESUMEN
Talaromyces (Penicillium) marneffei is an intracellular pathogenic fungus. Some strains of this fungus have been misidentified due to the similarity between Talaromyces and Penicillium. T. marneffei has mainly been found to afflict immunocompromised individuals, causing respiratory, skin, and systemic mycosis. Mp1p is a key virulence factor that can help T. marneffei evade clearance by the normally functioning immune system. Understanding how novel functions arise is an intriguing question in many fields of biology. Mp1p has two homologous domains (Mp1p-LBD1 and Mp1p-LBD2). Sequence similarity searches with Mp1p-LBD sequences revealed Mp1p homologs in many other pathogenic fungi. Integrated information on the taxonomic distribution, phylogenetic relationships, and sequence similarity of Mp1p domains revealed that the ancestor of Mp1p-LBDs was acquired through horizontal gene transfer (HGT). Additional evidence revealed that Mp1p homologs have undergone extensive gene duplications in T. marneffei. Mp1p might be a result of gene fusion following gene duplication. Furthermore, we propose a new method for identifying Talaromyces and identify 4 strains with misclassification errors. Our results characterize the evolutionary mechanism of T. marneffei evasion of host innate immune defense and clearly demonstrate the role of gene duplication and HGT in the evolution of host immune escape by T. marneffei.
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Micosis , Talaromyces , Humanos , Talaromyces/genética , Filogenia , Micosis/genética , Micosis/microbiología , Inmunidad Innata/genéticaRESUMEN
There is yet no effective drug for Alzheimer's disease (AD) which is one of the world's most common neurodegenerative diseases. The Qin-Zhi-Zhu-Dan Formula (QZZD) is derived from a widely used Chinese patent drug-Qing-Kai-Ling Injection. It consists of Radix Scutellariae, Fructus Gardeniae, and Pulvis Fellis Suis. Recent study showed that QZZD and its effective components played important roles in anti-inflammation, antioxidative stress and preventing brain injury. It was noted that QZZD had protective effects on the brain, but the mechanism remained unclear. This study aims to investigate the mechanism of QZZD in the treatment of AD combining network pharmacology approach with experimental validation. In the network pharmacology analysis, a total of 15 active compounds of QZZD and 135 putative targets against AD were first obtained. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then applied to clarify the biological mechanism. The anti-inflammatory mechanism of QZZD was proved, and a synthetic pathway-TNFR1-ERK1/2-NF-κBp65 signaling pathway was obtained. On the basis of the above discoveries, we further validated the protective effects QZZD on neurons with an APP/PS1 double transgenic mouse model. Weight change of the mice was monitored to assess QZZD's influence on the digestive system; water maze experiment was used for evaluating the effects on spatial learning and memory; Western blotting and immunohistochemistry analysis were used to detect the predicted key proteins in network pharmacology analysis, including Aß, IL-6, NF-κBp65, TNFR1, p-ERK1/2, and ERK1/2. We proved that QZZD could improve neuroinflammation and attenuate neuronal death without influencing the digestive system in APP/PS1 double transgenic mice with dementia. Combining animal pharmacodynamic experiments with network pharmacology analysis, we confirmed the importance of inflammation in pathogenesis of AD, clarified the pharmacodynamic characteristics of QZZD in treating AD, and proved its neuroprotective effects through the regulation of TNFR1-ERK1/2-NF-κBp65 signaling pathway, which might provide reference for studies on treatment of AD in the future.
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Background: Qinzhi Zhudan Formula (QZZD), optimized from Angong Niuhuang Wan, consists of Radix Scutellariae, Fructus Gardeniae and Pulvis Fellis Suis. We had investigated the neuroprotective effects of QZZD and its active components, and demonstrated that it could treat cerebral ischemia and dementia through multiple pathways and mechanisms. Nevertheless, toxicological data on this formula still remains limited. In the study, we sought to examine the toxicological effects of QZZD during the treatment and recovery periods. Methods: We investigated potential toxicities of QZZD in Sprague-Dawley (SD) rats via 28-day gavage administration. SD rats were randomly divided into control group and treatment groups of A (0.5 g/kg/d QZZD), B (1.5 g/kg/d QZZD), and C (5.0 g/kg/d QZZD). The 56-day course includes treatment period (administration with water or QZZD once a day for 28 consecutive days) and recovery period (28 days). The rats received daily monitoring of general signs of toxicity and mortality, as well as weekly determination of body weight and food consumption. Moreover, the complete blood cell count, biochemistry, coagulation, and urine indicators, organ weights, and histopathological report were analyzed respectively at the end of the treatment and recovery periods. Results: There was no death related to the active pharmaceutical ingredients of QZZD during the treatment period. The maximum no observed adverse effect level (NOAEL) was 0.5 g/kg/d, which is approximately 16.7 times of the equivalent dose of clinical dose in rats. In group TB (1.5 g/kg/d QZZD) and TC (5.0 g/kg/d QZZD), there were adverse effects of blue coloring of tail skin, weight loss, a significant increase of total bilirubin (TBIL), blackening of liver and kidney in gross examination, hyperplasia of bile duct and karyomegaly of hepatocytes in histopathological examination. Besides, in females rats, the food consumption was reduced, while in male rats, there was decrease in triglycerides (TG) and slight increase in white blood cell (WBC) count and neutrophils. In group TC (5.0 g/kg/d QZZD), the indicators of red blood cell (RBC) count, hemoglobin (HGB) and hematocrit (HCT) were decreased slightly, while the platelet count (PLT) was increased. However, these changes were not considered to be toxicologically significant because they resolved during the recovery period. Conclusion: Overall, QZZD exhibited a good safety profile. The maximum no observed adverse effect level was 0.5 g/kg/d, and no target organs toxicity were identified. The present findings might confirm the safety of QZZD in clinical practices.
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Based on the theory of consolidating the root and cultivating the primary, the paper collates and reviews the theoretical evidences and the characteristics of Xin'an medical masters in treatment of bi syndrome with acupuncture and moxibustion so as to provide the ideas for further research. Xin'an medical masters thoroughly acquainted with the theory of consolidating the root and cultivating the primary in treatment of bi syndrome with acupuncture and moxibustion, emphasizing the regulation of qi and blood, yin and yang, the nutrient qi and the defensive qi; and replenishing the middle jiao (spleen and stomach) and the lower jiao (kidney). The acupoint selection was distinctive, in which, the acupoints were selected and stimulated in terms of the etiology and the pathogenesis of diseases, as well as the properties of special points. The remarkable therapeutic effect on bi syndrome was ensured through specially selecting he-sea points, ashi points and "yin-yang opposite" points; effectively using the penetrating needling technique and moxibustion method and combining acupuncture with herbal medication.
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Terapia por Acupuntura , Acupuntura , Moxibustión , Puntos de Acupuntura , BazoRESUMEN
Background: Vestibular schwannoma (VS) is the most common benign tumor of the posterior fossa. The recurrence of VS has always received widespread attention. This study aimed to develop a nomogram to predict Recurrence-free survival (RFS) following resection of VS. Methods: A total of 425 patients with VS who underwent resection at the Department of Neurosurgery in Chinese PLA General Hospital between January 2014 and December 2020 were enrolled in this retrospective study. The medical records and follow-up data were collected. Cox regression analysis was used to screen prognostic factors and construct the nomogram. The predictive accuracy and clinical benefits of the nomogram were validated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Results: The Cox regression analysis revealed that age (HR = 0.96; 95% CI 0.94 - 0.99; p < 0.01), EOR (HR = 4.65; 95% CI 2.22 - 9.74; p < 0.001), and Ki-67 (HR = 1.16; 95% CI 1.09 - 1.23; p < 0.001) were all significantly correlated with recurrence, and they were finally included in the nomogram model. The concordance index of the nomogram was 0.86. The areas under the curve (AUCs) of the nomogram model of 3-, 4- and 5-year were 0.912, 0.865, and 0.809, respectively. A well-fitted calibration curve was also generated for the nomogram model. The DCA curves also indicated that the nomogram model had satisfactory clinical utility compared to the single indicators. Conclusions: We developed a nomogram that has high accuracy in predicting RFS in patients after resection of VS. All of the included prognostic factors are easy to obtain. The nomogram can improve the postoperative management of patients and assist clinicians in individualized clinical treatment. Furthermore, we generated a web-based calculator to facilitate clinical application: https://abc123-123.shinyapps.io/VS-RFS/.
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Background: Glioma is globally recognised as one of the most frequently occurring primary malignant brain tumours, making the identification of glioma biomarkers critically significant. The protein KIF18A (Kinesin Family Member 18A) is a member of the kinesin superfamily of microtubule-associated molecular motors and has been shown to participate in cell cycle and mitotic metaphase and anaphase. This is the first investigation into the expression of KIF18A and its prognostic value, potential biological functions, and effects on the immune system and mitosis in glioma patients. Methods: Gene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. Statistical analysis was conducted in R software. Clinical samples were used to evaluate the expression of KIF18A via immunohistochemical staining. In addition, the expression level of KIF18A was validated on U87 cell line. Results: Our results highlighted that KIF18A plays a key role as an independent prognostic factor in patients with glioma. KIF18A was highly expressed in glioma tissues, and KIF18A expression was associated with age, World Health Organization grade, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion, primary therapy outcome, and overall survival (OS). Enrichment analysis revealed that KIF18A is closely correlated with the cell cycle and mitosis. Single sample gene set enrichment analysis (ssGSEA) analysis revealed that KIF18A expression was related to the immune microenvironment. The increased expression of KIF18A in glioma was verified in clinical samples and U87 cell line. Conclusion: The identification of KIF18A as a new biomarker for glioma could help elucidate how changes in the glioma cell and immune microenvironment promote glioma malignancy. With further analysis, KIF18A may serve as an independent prognostic indicator for human glioma.
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OBJECTIVE: This study evaluated the characteristics of vestibular schwannomas (VS) in young patients, including clinical features, treatment, prognosis, and histopathologic characteristics. METHODS: We retrospectively reviewed medical records and follow-up data for 36 pediatric patients <21 years of age who were surgically treated for VS in the Chinese PLA General Hospital between 2008 and 2019. RESULTS: Mean patient age was 17.4 years. Mean tumor size was 2.8 cm. Hearing loss (n = 32, 88.9%) and tinnitus (n = 20, 55.6%) were the most common symptoms. Ten patients (27.8%) had impaired facial nerve function after surgery. Gross total resection (GTR) was achieved in 26 cases (72.2%). The median tumor Ki-67 level was 5%. Tumor size was related to incomplete tumor resection (odds ratio, 0.2; 95% confidence interval, 0.1-0.9) and postoperative facial nerve dysfunction (odds ratio, 24.9; 95% confidence interval, 1.2-539.1). Tumor size was nonlinearly associated with prognosis and 2.2 cm corresponded to the inflection point at which the probability of tumor remnant and postoperative facial nerve dysfunction significantly increased. The GTR and low Ki-67 groups achieved better 3-year tumor control rate. Histopathologic findings confirmed the presence of cellular schwannoma subtype in young patients. CONCLUSIONS: Tumor size is an important factor affecting the prognosis of VS in young patients. For large VS, surgical treatment should be the first choice, rather than wait-and-scan. VS in young patients shows high tumor proliferation and a tendency to relapse. The cellular schwannoma subtype requires special attention; an accurate histopathologic diagnosis is necessary for young patients with VS, and a closer follow-up strategy should be adopted for cellular VS.
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Neurilemoma , Neuroma Acústico , Adolescente , Niño , Nervio Facial/cirugía , Estudios de Seguimiento , Humanos , Antígeno Ki-67 , Recurrencia Local de Neoplasia/complicaciones , Neurilemoma/complicaciones , Neuroma Acústico/patología , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Object detection in point cloud data is one of the key components in computer vision systems, especially for autonomous driving applications. In this work, we present Voxel-Feature Pyramid Network, a novel one-stage 3D object detector that utilizes raw data from LIDAR sensors only. The core framework consists of an encoder network and a corresponding decoder followed by a region proposal network. Encoder extracts and fuses multi-scale voxel information in a bottom-up manner, whereas decoder fuses multiple feature maps from various scales by Feature Pyramid Network in a top-down way. Extensive experiments show that the proposed method has better performance on extracting features from point data and demonstrates its superiority over some baselines on the challenging KITTI-3D benchmark, obtaining good performance on both speed and accuracy in real-world scenarios.