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Allogeneic tumors are eradicated by host immunity; however, it is unknown how it is initiated until the report in Nature by Yaron Carmi et al. in 2015. Currently, we know that allogeneic tumors are eradicated by allogeneic IgG via dendritic cells. AlloIgG combined with the dendritic cell stimuli tumor necrosis factor alpha and CD40L induced tumor eradication via the reported and our proposed potential signaling pathways. AlloIgG triggers systematic immune responses targeting multiple antigens, which is proposed to overcome current immunotherapy limitations. The promising perspectives of alloIgG immunotherapy would have advanced from mouse models to clinical trials; however, there are only 6 published articles thus far. Therefore, we hope this perspective view will provide an initiative to promote future discussion.
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With the rapid progression of agricultural informatization technology, the methodologies of crop monitoring based on spectral technology are constantly upgraded. In order to carry out the efficient, precise and nondestructive detection of relative chlorophyll (SPAD) during the booting stage, we acquired hyperspectral reflectance data about spring wheat vertical distribution and adopted the fractional-order differential to transform the raw spectral data. After that, based on correlation analysis, fractional differential spectra and fractional differential spectral indices with strong correlation with SPAD were screened and fused. Then, the least-squares support vector machine (LSSSVM) and the least-squares support vector machine (SMA-LSSSVM) optimized on the slime mold algorithm were applied to construct the estimation models of SPAD, and the model accuracy was assessed to screen the optimal estimation models. The results showed that the 0.4 order fractional-order differential spectra had the highest correlation with SPAD, which was 9.3% higher than the maximum correlation coefficient of the original spectra; the constructed two-band differential spectral indices were more sensitive to SPAD than the single differential spectra, in which the correlation reached the highest level of 0.724. The SMA-LSSSVM model constructed based on the two-band fractional-order differential spectral indices was better than the single differential spectra and the integration of both, which realized the assessment of wheat SPAD.
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Imageamento Hiperespectral , Triticum , Análise Espectral , Folhas de Planta , Análise dos Mínimos QuadradosRESUMO
Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.
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Necrose da Cabeça do Fêmur , Glucocorticoides , Microvasos , Humanos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/etiologia , Microvasos/patologia , Glucocorticoides/efeitos adversos , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/patologia , Microcirculação , Neovascularização Patológica/etiologiaRESUMO
T-tubes and airway stents are commonly used but have limited effectiveness and frequent complications. A 50-year-old male patient presented with severe tracheal stenosis, affecting an 8.7 cm length of the airway. We employed an innovative approach known as external suspension fixation of tracheal stent using robotic assistance. This method involves surgically attaching the stent to the exterior of the trachea to provide support and stabilize the softened or collapsed tracheal segments. We designed a C-shaped nickel-titanium alloy exterior stent and successfully fixed it using robotic assistance. This intervention effectively restored tracheal function and led to a favorable postoperative recovery. The technique does not affect tracheal membrane function or airway mucociliary clearance. It could potentially be considered as a new option for treating long-segment benign tracheal softening or collapse.
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Níquel , Desenho de Prótese , Procedimentos Cirúrgicos Robóticos , Stents , Titânio , Estenose Traqueal , Humanos , Masculino , Pessoa de Meia-Idade , Estenose Traqueal/cirurgia , Estenose Traqueal/diagnóstico por imagem , Estenose Traqueal/etiologia , Estenose Traqueal/fisiopatologia , Resultado do Tratamento , LigasRESUMO
In the field of diagnosing lung diseases, the application of neural networks (NNs) in image classification exhibits significant potential. However, NNs are considered "black boxes," making it difficult to discern their decision-making processes, thereby leading to skepticism and concern regarding NNs. This compromises model reliability and hampers intelligent medicine's development. To tackle this issue, we introduce the Evolutionary Neural Architecture Search (EvoNAS). In image classification tasks, EvoNAS initially utilizes an Evolutionary Algorithm to explore various Convolutional Neural Networks, ultimately yielding an optimized network that excels at separating between redundant texture features and the most discriminative ones. Retaining the most discriminative features improves classification accuracy, particularly in distinguishing similar features. This approach illuminates the intrinsic mechanics of classification, thereby enhancing the accuracy of the results. Subsequently, we incorporate a Differential Evolution algorithm based on distribution estimation, significantly enhancing search efficiency. Employing visualization techniques, we demonstrate the effectiveness of EvoNAS, endowing the model with interpretability. Finally, we conduct experiments on the diffuse lung disease texture dataset using EvoNAS. Compared to the original network, the classification accuracy increases by 0.56%. Moreover, our EvoNAS approach demonstrates significant advantages over existing methods in the same dataset.
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ETHNOPHARMACOLOGICAL RELEVANCE: In China, Xanthoceras sorbifolium Bunge was first documented as "Wen Guan Hua" in the "Jiu Huang Ben Cao" in 1406 A.D. According to the "National Compilation of Chinese Herbal Medicine," X. sorbifolium leaves are sweet and flat in nature and can dispel wind and dampness, suggesting that their extract can be used to treat rheumatoid arthritis. X. sorbifolium Bunge has also been used to treat arteriosclerosis, hyperlipidemia, hypertension, chronic hepatitis, and rheumatism, complications associated with hyperuricemic nephropathy (HN), a condition characterized by kidney damage resulting from high levels of uric acid (UA) in the blood. AIM OF THE STUDY: The purpose of this study was to investigate the effects and underlying mechanisms of a 70% ethanol extract from X. sorbifolium leaves (EX) in alleviating HN. MATERIALS AND METHODS: A mouse model of hyperuricemia was established to initially evaluate the hypouricemic effects and determine the effective dose of EX. Phytochemical analyses were conducted using ultra high-performance liquid chromatography and liquid chromatography-mass spectroscopy. The potential key pathways of EX in the alleviation of HN were inferred using network pharmacology and bioinformatics. An HN rat model was then established, and experiments including biomarker detection, western blotting, reverse transcription quantitative polymerase chain reaction, immunohistochemical and Masson's trichrome staining, and transmission electron microscopy were conducted to evaluate the effect of EX on UA transporter expression in vitro. RESULTS: Network pharmacology and bioinformatics analyses revealed that the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was the key pathway for the alleviation of HN progression by EX. EX treatment reduced serum biomarkers in HN rats, downregulated the expression of p-PI3K, p-AKT, glucose transporter 9 (GLUT9), urate transporter 1 (URAT1), Collagen I, matrix metalloproteinase (MMP)-2, and MMP-9, and upregulated the expression of ATP binding cassette subfamily G member 2 (ABCG2) to improve renal interstitial fibrosis in HN rats. A high content of both quercitrin and cynaroside were identified in EX; their administration inhibited the increased expression of GLUT9 and URAT1 in damaged HK-2 cells. CONCLUSION: Our study provides evidence that EX alleviates HN. The potential mechanism underlying this effect may be the regulation of UA transporters, such as GLUT9 and URAT1, by limiting the activation of the PI3K/AKT signaling pathway to improve renal injury.
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Hiperuricemia , Nefropatias , Camundongos , Ratos , Animais , Ácido Úrico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Rim , Nefropatias/metabolismo , Transdução de Sinais , Biomarcadores/metabolismoRESUMO
Lung cancer is currently the second most common type of cancer with the second incidence rate and the first mortality rate worldwide. Nonsmall cell lung cancer (NSCLC) accounts for ~85% of the total number of cases of lung cancers. Concerning the treatment of NSCLC, targeted therapy has become a research hotspot in recent years because of its favorable efficacy, high selectivity and minimal adverse reactions. Among the drugs used in targeted therapy, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the most common and are categorized into four generations. The use of first and secondgeneration drugs leads to drug resistance within 814 months. This resistance is primarily caused by the T790M mutation, which is the most observed mechanism. A thirdgeneration drug has been developed to address this issue and a fourthgeneration drug is expected to overcome multiple resistance mechanisms, including thirdgeneration drug resistance. However, the fourthgeneration drug has not been launched yet. At present, multiple thirdgeneration targeted drugs have been launched globally, with three being launched in China and several being at research and clinical trial stages. The present article provides a review of the development process, mechanism of action and clinical trials of the thirdgeneration EGFRTKIs, aiming to provide some reference and suggestions for the clinical treatment of NSCLC and scientific research on thirdgeneration targeted drugs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , /uso terapêuticoRESUMO
Current treatments for orthopaedic illnesses frequently result in poor prognosis, treatment failure, numerous relapses, and other unpleasant outcomes that have a significant impact on patients' quality of life. Cell-free therapy has emerged as one of the most promising options in recent decades for improving the status quo. As a result, using exosomes produced from various cells to modulate ferroptosis has been proposed as a therapeutic method for the condition. Exosomes are extracellular vesicles that secrete various bioactive chemicals that influence disease treatment and play a role in the genesis and progression of orthopaedic illnesses. Ferroptosis is a recently defined kind of controlled cell death typified by large iron ion buildup and lipid peroxidation. An increasing number of studies indicate that ferroptosis plays a significant role in orthopaedic illnesses. Exosomes, as intercellular information transfer channels, have been found to play a significant role in the regulation of ferroptosis processes. Furthermore, accumulating research suggests that exosomes can influence the course of many diseases by regulating ferroptosis in injured cells. In order to better understand the processes by which exosomes govern ferroptosis in the therapy of orthopaedic illnesses. This review discusses the biogenesis, secretion, and uptake of exosomes, as well as the mechanisms of ferroptosis and exosomes in the therapy of orthopaedic illnesses. It focuses on recent research advances and exosome mechanisms in regulating iron death for the therapy of orthopaedic illnesses. The present state of review conducted both domestically and internationally is elucidated and anticipated as a viable avenue for future therapy in the field of orthopaedics.
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Exossomos , Ferroptose , Ferroptose/fisiologia , Humanos , Exossomos/metabolismo , Animais , Ferro/metabolismoRESUMO
To better understand the palatable properties of Xuanwei ham, the aqueous extract was isolated, analyzed and combin with sensory evaluation. Of umami-tasting activity and umami-enhancing impact, four new peptides (MDAIKKMQ, RKYEEVAR, YVGDEAQSKRG, and VNVDEVGGEALGR) were extracted and identified by ultrafiltration, gel separation, reverse performance liquid chromatography, and nano-LC-MS / MS. Sensory evaluation results showed that all of them had umami activity and enhanced umami taste, among which VNVDEVGGEALGR had the best effect. These peptides' umami taste thresholds ranged from 0.25 to 0.8 mg/mL. The MSG solution's umami taste threshold ranged from 0.125 to 0.5 mg/mL. Molecular docking results showed that the four umami peptides could be embedded into the binding pocket of the T1R3 cavity of the umami taste receptor T1R1/T1R3, wherein the binding sites Asp219, Asp150, and Thr179 may play crucial roles, and Glu222, Asp108, Glu217 and Glu148 play auxiliary roles. Hydrogen bonding and hydrophobic interactions were the most prominent interaction forces. This study helps to clarify the flavor characteristics of Xuanwei ham and could improve new processing technology.
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Peptídeos , Paladar , Simulação de Acoplamento Molecular , Peptídeos/química , Sítios de Ligação , Espectrometria de MassasRESUMO
Subtilisin-like proteases (subtilases) are found in almost all plant species and are involved in regulating various biotic and abiotic stresses. Although the literature on subtilases in different plant species is vast, the gene function of the serine peptidase S8 family and its maize subfamily is still unknown. Here, a bioinformatics analysis of this gene family was conducted by describing gene structure, conserved motifs, phylogenetic relationships, chromosomal distributions, gene duplications, and promoter cis-elements. In total, we identified 18 ZmSPS8 genes in maize, distributed on 7 chromosomes, and half of them were hydrophilic. Most of these proteins were located at the cell wall and had similar secondary and tertiary structures. Prediction of cis-regulatory elements in promoters illustrated that they were mainly associated with hormones and abiotic stress. Maize inbred lines B73, Zheng58, and Qi319 were used to analyze the spatial-temporal expression patterns of ZmSPS8 genes under drought treatment. Seedling drought results showed that Qi319 had the highest percent survival after 14 d of withholding irrigation, while B73 was the lowest. Leaf relative water content (LRWC) declined more rapidly in B73 and to lower values, and the nitrotetrazolium blue chloride (NBT) contents of leaves were higher in Qi319 than in the other inbreds. The qPCR results indicated that 6 serine peptidase S8 family genes were positively or negatively correlated with plant tolerance to drought stress. Our study provides a detailed analysis of the ZmSPS8s in the maize genome and finds a link between drought tolerance and the family gene expression, which was established by using different maize inbred lines.
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As one of the most common malignant tumors, hepatocellular carcinoma (HCC) has a rising incidence rate and also seriously endangers human life and health. According to research reports, hepatitis B, hepatitis C, intake of aflatoxin in the diet, and the effects of alcohol and other chemicals can induce an increase in the incidence of liver cancer. However, in the current clinical treatment of HCC, most of the drugs are chemical drugs, which have relatively large side effects and are prone to drug resistance. Therefore, the development of natural compounds to treat HCC has become a new treatment strategy. Several studies have shown that flavonoids have shown outstanding effects and exhibit strong tumor growth inhibitory effects in vivo experimental studies. Luteolin, as a natural flavonoid, has anti-tumor, anti-inflammatory, anti-viral, anti-oxidation, immune regulation, and other pharmacological effects. The anti-cancer mechanism of luteolin mainly directly acts on tumor cells to inhibit their growth, induce cell apoptosis, reduce tumor tissue angiogenesis, regulate long non-coding RNA, affect immunogenic cell death, and regulate autophagy. As well as improving the curative effect of radiotherapy and chemotherapy and chemoprevention. In this study, we evaluated the function of luteolin in regulating cancer cell proliferation, migration, and invasion will summarize and analyze luteolin and its mechanism of regulating HCC to improve the role of luteolin in the clinical prevention and treatment of HCC.
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Ovarian cancer (OC) is a common and highly prevalent malignant tumor in women, associated with a high mortality rate, easy recurrence and easy metastasis, which is predominantly at an advanced stage when detected in patients. This renders the cancer more difficult to treat, and consequently it is also associated with a low survival rate, being the malignancy with the highest mortality rate among the various gynecological tumors. As an important factor affecting the development and metastasis of OC, understanding the underlying mechanism(s) through which it is formed and developed is crucial in terms of its treatment. At present, the therapeutic methods of angiogenic mimicry for OC remain in the preliminary stages of exploration and have not been applied in actual clinical practice. In the present review, various signaling pathways and factors affecting angiogenic mimicry in OC were described, and the chemical synthetic drugs, natural compound extracts, small-molecule protein antibodies and their associated targets, and so on, that target angiogenic mimicry in the treatment of OC, were discussed. The purpose of this review was to provide new research ideas and potential theoretical support for the discovery of novel therapeutic targets for OC that may be applied in the clinic, with the aim of effectively reducing its metastasis and recurrence rates.
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Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency. Clinically, it is most frequently observed in people with alcohol abuse. WE, however, can occur in any clinical condition associated with malnutrition or thiamine deficiency. We present the case of a 47-year-old woman with prolonged therapeutic fasting who presented with ophthalmoplegia, ataxia and deep coma. MRI showed unusual symmetric cortical abnormalities in the frontal and parietal lobes, as well as typical lesions surrounding the third ventricle and aqueduct. Although the patient entered a vegetative state, she finally regained consciousness after thiamine supplementation unexpectedly. To the best of our knowledge, it has never been reported to date that the patient with WE in a vegetative state with cortical damage shows a marvelous prognosis, which prompts us to report this case. In the present report, we highlight the role of MRI in the diagnosis of acute WE.
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Pancreatite/complicações , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/etiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Pessoa de Meia-Idade , Lobo Parietal/patologia , Substância Cinzenta Periaquedutal/patologia , Tálamo/patologiaRESUMO
We investigated a possible association between genetic variations in chloride channel Kb (CLCNKB) gene and essential hypertension (EH) in the Mongolian and Han populations in Inner Mongolia. Our study included 414 unrelated Mongolian herdsmen and 524 Han farmers. Two tagSNPs of CLCNKB (rs945393 and rs10803414) were identified from the Chinese HapMap database based on pairwise r(2) ≥ 0.5 and minor allele frequency ≥0.05. Genotyping was performed using the PCR/ligase detection reaction assay. There was significant difference in allele frequency of rs10803414 between the EH group (35%) and the control group (26%) in the Mongolian population (P < .05). Significant association was identified between rs10803414 and EH in the Mongolian population (P < .05) and rs945393 and EH in the Han population (P < .01). The frequency of haplotype CC in the EH group (9.4%) was significantly higher than in the control group (4.6%) in the Mongolian population; individuals who possessed the CC haplotype had a significantly higher risk of EH in the Mongolian population. There was no association between haplotype and EH in the Han population. After adjusting for age, sex, and other confounding risk factors, only rs10803414 was the risk factor of hypertension in Mongolians. Our results indicate that rs10803414 in CLCNKB confers a significant risk of EH in the Mongolian population and haplotype CC of CLCNKB is a genetic factor for EH in the Mongolian population. Our study expands the association between CLCNKB and EH to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of EH locus.
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Povo Asiático/genética , Canais de Cloreto/genética , Frequência do Gene/genética , Hipertensão/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença/genética , Genótipo , Haplótipos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mongólia , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto JovemRESUMO
Objective: Although the prognosis of posterior reversible encephalopathy syndrome (PRES) is usually favourable and most patients wholly recover, the disorder can result in death in some patients. To date, the data on clinical features and risk factors for death are still lacking; therefore, we aim to investigate the clinical features and long-term prognostic risk factors of PRES in the present study. Methods: The patients with PRES were identified from the First Affiliated Hospital of Zhengzhou University from June 2011 to June 2020. Clinical characteristics, laboratory tests, magnetic resonance imaging examinations, and treatment of all patients were analyzed retrospectively. All patients were followed up by telephone. Finally, the patients were divided into the survival group and death group for prognosis analysis. Results: A total of 92 patients with PRES were included; 84.8% of whom were female, with an average age of 25.4 (5-66) years at the onset of PRES. Epilepsy was the main clinical manifestation (72.8%). The in-hospital mortality rate was 2.17%. The 3-year all-cause survival rate for PRES patients was 86%. In univariate analysis, patients with systemic lupus erythematosus (P = 0.027) and blood transfusion history within 1 month before onset (P = 0.027), need for dialysis (P ≤ 0.001), nephritis (P = 0.010), stroke (P = 0.016), and heart failure (P = 0.016) were associated with death. In multivariate analysis, we found that heart failure (OR = 0.095, 95% CI 0.020 to 0.441) and stroke (OR = 0.033, 95% CI 0.002 to 0.467) were independent risk factors for death in PRES patients, while pregnancy was a protective factor for death in PRES patients (OR = 7.978, 95% CI 1.446 to 44.006). Conclusions: Our results indicate that PRES could be considered as a sign of a very high-risk patient. We also demonstrated that heart failure and stroke were independent risk factors for death in patients with PRES; moreover, pregnancy was a protective factor.
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Insuficiência Cardíaca , Síndrome da Leucoencefalopatia Posterior , Acidente Vascular Cerebral , Humanos , Feminino , Adulto , Masculino , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/complicações , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
Under the restriction of the national "double carbon" goal, how to realize the coordination between urbanization and low-carbon development in the Yellow River Basin is a problem worthy of attention. In this paper, a new urbanization and ecological carrying capacity evaluation index system is established to evaluate the new urbanization level and ecological carrying capacity of the Yellow River Basin. On this basis, the uncoordinated coupling level of new urbanization and ecological carrying capacity in the Yellow River Basin is measured by using the improved uncoordinated coupling model, and its temporal and spatial characteristics and internal impact mechanism are analyzed. The study shows that the new urbanization and ecological carrying capacity of the Yellow River Basin has a benign development trend as a whole. Shandong province belongs to the low-level uncoordinated coupling type; Gansu Province and Qinghai Province belong to the running-in uncoordinated type; and Shanxi Province, the Inner Mongolia Autonomous Region, Shaanxi Province, and the Ningxia Hui Autonomous Region belong to the antagonistic uncoordinated coupling type. The uncoordinated coupling degree between new urbanization and ecological carrying capacity in the Yellow River Basin has a spatial interaction effect. It presents a low-level cluster centered on Shaanxi Province and Shandong Province and a high-level cluster centered on Gansu Province, Qinghai Province, and the Ningxia Hui Autonomous Region. From the perspective of the internal main impact mechanism, water resources have a two-way impact on the development of the two systems of new urbanization and ecological carrying capacity; the number of permanent residents and the level of scientific and technological investment have a one-way impact on the process of new urbanization; and the green coverage rate of built-up areas has a one-way impact on the development of ecological carrying capacity. The main contributions of this paper are as follows. First, the evaluation index system of new urbanization and ecological carrying capacity has been improved in combination with the new development concept. The evaluation of new urbanization by this index system is more in line with the current national requirements for high-quality development. Second, the impact of potential resources and human regulation has been added to the traditional ecological carrying capacity evaluation index system, and the evaluation of ecological carrying capacity by this index system is more in line with reality. Thirdly, taking the time effect into account, an improved uncoordinated coupling method is proposed. Using this method to evaluate the relationship between systems is conducive to bringing the dynamic relationship within the system into the evaluation system, which is more in line with the reality of system changes. Fourth, from the perspective of problem diagnosis, research on the relationship between new urbanization and ecological carrying capacity will help to find the internal mechanism that affects the coordinated development of new urbanization and ecological carrying capacity in the Yellow River Basin. This method is universal for exploring the internal influence mechanism of the relationship between systems.
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Conservação dos Recursos Naturais , Urbanização , Carbono , China , Ecossistema , Humanos , RiosRESUMO
Renal cell carcinoma (RCC), one of the most frequent cancers, is a "classical" malignancy characterized by metabolic reprogramming. Clear cell renal cell carcinoma (ccRCC) is its most common histopathological subtype. Long-stranded non-coding ribonucleic acids (LncRNAs) are regulatory RNA molecules with limited protein-coding capacity and evolutionary conservation. Recent studies have revealed that lncRNAs can broadly regulate the metabolic reprogramming of ccRCC and its malignant transformation. However, there are few studies on lncRNAs regulating the metabolism of ccRCC, and the specific mechanisms are unknown. Therefore, this paper summarizes the regulatory mechanisms of lncRNAs in the metabolism of ccRCC, especially in the pathways of glycolysis, mitochondrial function, glutamine and lipid metabolism, cellular mechanisms, interactions with other molecules, specific scientific and clinic implications and applications to provide a basis for early clinical diagnosis, prediction and treatment. We also discuss the clinical application and challenges of targeting lncRNAs in ccRCC metabolism.
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OBJECTIVES: N6-methyladenosine (m6A), a predominant RNA modification, has been recently linked to messenger RNA splicing, stability and expression, and its dysregulation may be important in the initiation as well as development of human cancers. The current study was proposed to investigate the clinico-pathological value and multiomic characteristics of m6A-linked genes in the diagnosis and prognosis of lung adenocarcinoma (LUAD). METHODS: The expression levels and mutation types of 21 previously identified m6A regulators were analyzed using the TCGA (The Cancer Genome Atlas) database. The patients were categorized into two groups, a training group (n=392) and a testing group (n=98). Next, the prognostic score of m6A regulators was determined by the Cox survival analysis and a regression model of LASSO to develop a risk profile for patients with LUAD. Moreover, features of risk signature, including chemosensitivity, tumor immune microenvironment and genetic mutation, were also explored. RESULTS: In total, 18 of 21 m6A regulators showed significantly differential expression in LUAD (P<0.05). Among them, 6 genes were observed to be associated with the Overall Survival (OS) of patients with LUAD. Three genes (IGF2BP1 and 2, and HNRNPC) were further evaluated as a prognostic signature in LUAD. Patients, grouped as high risk based on the median of risk score, had poorer OS in comparison with those in low-risk group (P<0.05). The accuracy of our prognostic signatures was high: the AUC were 0.67, 0.59, 0.64 (training set), and 0.65, 0.69, 0.64 (testing set) at survival of 1- , 3- and 5-year, respectively. The prognostic performance of IGF2BP1, IGF2BP2 and HNRNPC was successfully validated in two independent external cohorts. High-risk score was an indicator of chemoresistance, TP53 mutation and increased infiltration of immune cells, and in vitro assessment of the cellular function of HNRNPC confirmed that the gene is involved in cell proliferation and invasion. CONCLUSION: The prognostic signature based on m6A regulators might provide novel insights into prognostic assessment and individualized treatment for patients with LUAD.
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Acute respiratory distress syndrome (ARDS) is an acute lung injury associated with high morbidity and mortality. This study aimed to establish an accurate prediction model for mortality risk in ARDS. 70% of patients from the Medical Information Mart for Intensive Care Database (MIMIC-III) were selected as the training group, and the remaining 30% as the testing group. Patients from a Chinese hospital were used for external validation. Univariate and multivariate regressions were used to screen the independent predictors. The receiver operating characteristic curve (ROC) analysis, the Hosmer-Lemeshow test, and the calibration curve were used for evaluating the performance of the model. Age, hemoglobin, heart failure, renal failure, Simplified Acute Physiology Score II (SAPS II), immune function impairment, total bilirubin (TBIL), and PaO2/FiO2 were identified as independent predictors. The algorithm of the prediction model was: ln (Pr/(1 + Pr)) = -3.147 + 0.037 ∗ age - 0.068 ∗ hemoglobin + 0.522 ∗ heart failure (yes) + 0.487 ∗ renal failure (yes) + 0.029 ∗ SAPS II + 0.697 ∗ immune function impairment (yes) + 0.280 ∗ TBIL (abnormal) - 0.006 ∗ PaO2/FiO2 (Pr represents the probability of death occurring). The AUC of the model was 0.791 (0.766-0.816), and the internal and the external validations both confirmed the good performance of the model. A nomogram for predicting the risk of death in ARDS patients was developed and validated. It may help clinicians early identify ARDS patients with high risk of death and thereby help reduce the mortality and improve the survival of ARDS.
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Nomogramas , Síndrome do Desconforto Respiratório , Humanos , Recém-Nascido , Unidades de Terapia Intensiva , Curva ROCRESUMO
BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are often coincident, and each condition is considered a risk factor for the other. Both occur frequently in the Inner Mongolia region of China. The reasons for differences in risk between Han and Mongolian ethnic groups are not known. The LEPR gene and its polymorphism, rs1137101 (Gln223Arg), are both considered risk factors for HTN and T2DM, but any role of rs1137101 in the occurrence of HTN + T2DM remains unclear for Mongolian and Han populations in the Inner Mongolia region. AIM: To investigate the relationship between rs1137101 and the occurrence of HTN with T2DM in Mongolian and Han populations in Inner Mongolia. METHODS: A total of 2652 subjects of Han and Mongolian ethnic origins were enrolled in the current study, including 908 healthy controls, 1061 HTN patients and 683 HTN patients with T2DM. RESULTS: The association between the rs1137101 polymorphism and HTN with T2DM was analyzed, and differences between Han and Mongolian individuals assessed. There was a significant correlation between rs1137101 and HTN (co-dominant, dominant, over-dominant and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) after adjustment for sex and age in individuals of Mongolian origin. rs1137101 was significantly associated with HTN (co-dominant, recessive and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) in the Han Chinese population. CONCLUSION: Mongolian and Han subjects from Inner Mongolia with HTN who had rs1137101 were protected against the development of T2DM. Allele A has the opposite impact on the occurrence of HTN in Mongolian and Han Chinese populations.