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The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and a promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R's structure, activation, and physiological roles, focusing on its expression and function in microglial cells. The article examines the receptor's involvement in calcium signaling, microglial activation, and polarization, as well as its role in the pathogenesis of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. The review highlights the complex nature of P2X7R signaling, discussing its potential neuroprotective and neurotoxic effects depending on the disease stage and context. It also addresses the development of P2X7R antagonists and their progress in clinical trials, identifying key research gaps and future perspectives for P2X7R-targeted therapy development. By providing a comprehensive overview of the current state of knowledge and future directions, this review serves as a valuable resource for researchers and clinicians interested in exploring the therapeutic potential of targeting P2X7R for the treatment of neurodegenerative disorders.
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With the rapid development of traditional Chinese medicine and the continuous discovery of various anticancer effects of salidroside (sal), it is known that sal inhibits tumor proliferation, invasion and migration by inducing apoptosis and autophagy, regulating the cell cycle, modulating the tumor microenvironment, and controlling cancer-related signaling pathways and molecules. The microRNA (miRNA)-mRNA signaling axis can regulate the expression of target mRNAs by altering miRNA expression, thereby affecting the growth cycle, proliferation, and metabolism of cancer cells. Studies have shown that sal can influence the occurrence and progression of various malignant tumors through the miRNA-mRNA signaling axis, inhibiting the progression of lung cancer, gastric cancer, and nasopharyngeal carcinoma, with a notable time and dose dependence in its antitumor effects. Summarizing the specific mechanism of sal regulating miRNA-mRNA signaling axis to inhibit tumors in recent years can provide a new theoretical basis, diagnosis, and therapeutic methods for the research on prevention and treatment of tumors.
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Glucosídeos , MicroRNAs , Fenóis , RNA Mensageiro , Transdução de Sinais , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fenóis/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Microambiente Tumoral/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , AnimaisRESUMO
Temporal modulation recently draws great attentions in wave manipulations, with which one can introduce the concept of temporal multilayer structure, a temporal counterpart of spatially multilayer configurations. This kind of multilayer structure holds temporal interfaces in the time domain, which provides additional flexibility in temporal operations. Here we take this opportunity and propose to simulate a non-Abelian gauge field with a temporal multilayer structure in the discrete physical system. Two basic temporal operations, i.e., the folding/unfolding operation and the phase shift operation are used to design such a temporal multilayer structure, which hence can support noncommutative operations to realize the non-Abelian Aharonov-Bohm interference in the time domain. A two-/three-dimensional non-Abelian gauge field can be built, which may be further extended to higher dimensions. Our work therefore provides a unique platform enabling generalization of non-Abelian physics to arbitrary dimensions and offers a method for wave manipulations with temporal band engineering.
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This study aimed to develop a noninvasive predictive model for identifying early postoperative recurrence of hepatocellular carcinoma (within 2 years after surgery) based on contrast-enhanced ultrasound and serum biomarkers. Additionally, the model's validity was assessedthrough internal and external validation. Clinical data were collected from patients who underwent liver resection at the First Hospital of Quanzhou and Mengchao Hepatobiliary Hospital. The data included general information, contrast-enhanced ultrasound parameters, Liver Imaging Reporting and Data System (LI-RADS) classification, and serum biomarkers. The data from Mengchao Hospital were divided into 2 groups, with a ratio of 6:4, to form the modeling and internal validation sets, respectively. On the other hand, the data from the First Hospital of Quanzhou served as the external validation group. The developed model was named the Hepatocellular Carcinoma Early Recurrence (HCC-ER) prediction model. The predictive efficiency of the HCC-ER model was compared with other established models. The baseline characteristics were found to be well-balanced across the modeling, internal validation, and external validation groups. Among the independent risk factors identified for early recurrence, LI-RADS classification, alpha-fetoprotein, and tumor maximum diameter exhibited hazard ratios of 1.352, 1.337, and 1.135 respectively. Regarding predictive accuracy, the HCC-ER, Tumour-Node-Metastasis, Barcelona Clinic Liver Cancer, and China Liver Cancer models demonstrated prediction errors of 0.196, 0.204, 0.201, and 0.200 in the modeling group; 0.215, 0.215, 0.218, and 0.212 in the internal validation group; 0.210, 0.215, 0.216, and 0.221 in the external validation group. Using the HCC-ER model, risk scores were calculated for all patients, and a cutoff value of 50 was selected. This cutoff effectively distinguished the high-risk recurrence group from the low-risk recurrence group in the modeling, internal validation, and external validation groups. However, the calibration curve of the predictive model slightly overestimated the risk of recurrence. The HCC-ER model developed in this study demonstrated high accuracy in predicting early recurrence within 2 years after hepatectomy. It provides valuable information for developing precise treatment strategies in clinical practice and holds considerable promise for further clinical implementation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Segunda Neoplasia Primária , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Instituições de Assistência Ambulatorial , CalibragemRESUMO
Objectives: To construct a novel model based on contrast-enhanced ultrasound (CEUS) and serological biomarkers to predict the early recurrence (ER) of primary hepatocellular carcinoma within 2 years after hepatectomy. Methods: A total of 466 patients who underwent CEUS and curative resection between 2016.1.1 and 2019.1.1 were retrospectively recruited from one institution. The training and testing cohorts comprised 326 and 140 patients, respectively. Data on general characteristics, CEUS Liver Imaging Reporting and Data System (LI-RADS) parameters, and serological were collected. Univariate analysis and multivariate Cox proportional hazards regression model were used to evaluate the independent prognostic factors for tumor recurrence, and the Contrast-enhanced Ultrasound Serological (CEUSS) model was constructed. Different models were compared using prediction error and time-dependent area under the receiver operating characteristic curve (AUC). The CEUSS model's performances in ER prediction were assessed. Results: The baseline data of the training and testing cohorts were equal. LI-RADS category, α-fetoprotein level, tumor maximum diameter, total bilirubin level, starting time, iso-time, and enhancement pattern were independent hazards, and their hazards ratios were 1.417, 1.309, 1.133, 1.036, 0.883, 0.985, and 0.70, respectively. The AUCs of CEUSS, BCLC,TNM, and CNLC were 0.706, 0.641, 0.647, and 0.636, respectively, in the training cohort and 0.680, 0.583, 0.607, and 0.597, respectively, in the testing cohort. The prediction errors of CEUSS, BCLC, TNM, and CNLC were 0.202, 0.205, 0.205, and 0.200, respectively, in the training cohort and 0.204, 0.221, 0.219, and 0.211, respectively, in the testing cohort. Conclusions: The CEUSS model can accurately and individually predict ER before surgery and may represent a new tool for individualized treatment.
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BACKGROUND: Lenvatinib (LEN) is a first-line therapy for patients with hepatocellular carcinoma (HCC), but has a larger adverse effect profile. In this study, we developed a liposome with drug-carrying function and magnetic resonance imaging (MRI) imaging function to investigate the targeted drug-carrying function and MRI tracing ability of liposome for HCC. METHODS: Magnetic nano-liposomes (MNL) with dual targeting function of epithelial cell adhesion molecule (EpCAM) and vimentin and capable of encapsulating LEN drugs were prepared. The characterization performance, drug loading efficiency and cytotoxicity of EpCAM/vimentin-LEN-MNL were tested, and the dual-targeting slow release drug loading function and MRI tracing ability were investigated in cellular and animal models. RESULTS: EpCAM/vimentin-LEN-MNL has a mean particle size of 218.37 ± 5.13 nm and a mean potential of 32.86 ± 4.62 mV, and is spherical in shape and can be uniformly dispersed in solution. The encapsulation rate was 92.66 ± 0.73% and the drug loading rate was 9.35 ± 0.16%. It has low cytotoxicity, can effectively inhibit HCC cell proliferation and promote HCC cell apoptosis, and has specific targeting function and MRI tracing ability for HCC cells. CONCLUSIONS: In this study, an HCC-specific dual-targeted sustained-release drug delivery liposome with dual-targeted recognition and sensitive MRI tracer was successfully prepared, which provides an important scientific basis for maximizing the multiple effects of nano-carriers in tumor diagnosis and treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/metabolismo , Lipossomos , Preparações de Ação Retardada/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Vimentina/uso terapêutico , Molécula de Adesão da Célula Epitelial , Linhagem Celular TumoralRESUMO
This study focuses on the petrographic analysis method to evaluate semi-coke and its combustion behavior in the sintering process, which has been seldom conducted before. Semi-cokes are different in morphological features, porosity, pore structure, and wall thickness, because of differences in the vitrinite and inertinite of the raw coal. Semi-coke displayed isotropy, and even after the drop tube furnace (DTF) and sintering process, it still retained its optical properties. Eight kinds of sintered ash were observed using reflected light microscopy. Petrographic analyzes for the combustion properties of semi-coke were based on its optical structure, morphological development, and unburned char. The results indicated that microscopic morphology was an important characteristic when trying to understand the behavior and burnout of semi-coke. These characteristics can be used to trace the origin of the unburned char in fly ash. The unburned semi-coke mostly existed in the form of inertoid, mixed dense and mixed porous. Meanwhile, it was found that most of the unburned chars were melted into sinter, resulting in inefficient fuel combustion.
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The consensus algorithm is very critical in any blockchain system, because it directly affects the performance and security of the blockchain system. At present, the classic Practical Byzantine Fault Tolerance Algorithm (PBFT), which is mainly used in the consortium chain, will lead to system communication congestion and reduced throughput when the number of nodes increases, so the PBFT algorithm is not suitable for large-scale consortium chains. In response to the above problems, this paper proposes a new clustering-based sharding consensus algorithm (KBFT), which aims to ensure that the consortium chain takes into account decentralization, security and scalability. The KBFT algorithm first uses the K-prototype clustering algorithm to shard the nodes in the network according to mixed attributes, and second, disjoint transactions are used to reach consensus in parallel in different shards. Concurrently, the KBFT algorithm introduces a supervision mechanism and a node credit mechanism, which is used to supervise and score the behavior of the nodes and select the proxy nodes, which improves security. We discuss the choice of shard size with the help of the binomial probability distribution and analyze the probability that the system can successfully form a global block under different node failure probabilities. Finally, the proposed algorithm is evaluated through theoretical analysis and simulation experiments. Results show that the proposed algorithm achieves a marked improvement in scalability and throughput along with a marked reduction in communication complexity compared with the classic baseline algorithm PBFT in this field of study, which improves the operating efficiency of the system and simultaneously guarantees the security and robustness of the system.
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BACKGROUND Myeloablative chemotherapy supported by autologous stem cell transplantation (ASCT) is an option for primary central nervous system lymphoma (PCNSL) in both the relapse setting and as postremission consolidation, but the level of evidence in this field is still low. MATERIAL AND METHODS We retrospectively analyzed 47 HIV-negative PCNSL patients from 2010 to 2021. To assess the outcomes in patients undergoing ASCT. RESULTS Of the 47 patients, the median age was 51 (range, 21-77) years, and 28 (59.6%) were male. After induction, 33 (70.2%) patients achieved complete remission, and 6 (12.8%) patients achieved partial remission. At a median follow-up of 21.4 months (95% CI 8.86-33.95), the median progression-free survival (PFS) was 23.3 months (95% CI 14.87-31.73), and the 4-year PFS rate was 14.6%. The median overall survival (OS) time was 62.4 months (95% CI 41.93-82.87), and the 4-year OS rate was 71.5%. Among 20 patients who received ASCT (10 consolidation, 10 salvage), the 4-year PFS and 4-year OS rates were 57.3% and 71.2%, respectively. In the multivariate analysis, ASCT therapy (hazard ratio [HR] 0.16, P=0.016) and early remission (HR 0.12, p=0.003) were found to be independent prognostic factors for a longer PFS. Two treatment-related deaths occurred in patients with multiple relapses before ASCT. Pancytopenia and diarrhea were the most common adverse events. CONCLUSIONS ASCT offers potential long-term PFS with good tolerability for patients with PCNSL. Our retrospective cohort adds to the currently available literature and identifies disease status after induction as a significant factor affecting survival.
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Transplante de Células-Tronco Hematopoéticas , Linfoma , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva , Linfoma/cirurgia , Sistema Nervoso Central , Transplante de Células-TroncoRESUMO
The dimensionality of a physical system is one of the major parameters defining its physical properties. The recently introduced concept of synthetic dimension has made it possible to arbitrarily manipulate the system of interest and harness light propagation in different ways. It also facilitates the transformative architecture of system-on-a-chip devices enabling far reaching applications such as optical isolation. In this report, a novel architecture based on dynamically-modulated waveguide arrays with the Su-Schrieffer-Heeger configuration in the spatial dimension is proposed and investigated with an eye on a practical implementation. The propagation of light through the one-dimensional waveguide arrays mimics time evolution of the field in a synthetic two-dimensional lattice. The addition of the effective gauge potential leads to an exotic topologically protected one-way transmission along adjacent boundary. A cosine-shape isolated band, which supports the topological Bloch oscillation in the frequency dimension under the effective constant force, appears and is localized at the spatial boundary being robust against small perturbations. This work paves the way to improved light transmission capabilities under topological protections in both spatial and spectral regimes and provides a novel platform based on a technologically feasible lithium niobate platform for optical computing and communication.
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Anti-thymocyte globulin (ATG) is often included in the conditioning regimen to prevent graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo-HCT). However, the risk of virus reactivation increases significantly. We conducted a single-center prospective study to identify the optimal ATG exposure that ensures engraftment, effectively prevents acute GVHD, and reduces the risk of virus reactivation without increasing relapse of malignant diseases in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). From September 2018 to June 2020, 106 patients (median age, 32 years) with malignant hematological diseases who received haplo-PBSCT for the first time were enrolled. All patients received 10 mg/kg rabbit ATG (thymoglobulin) divided for 4 days (days -5 to -2). Pre-transplant, post-transplant, and total areas under the concentration-time curve (AUCs) of active ATG were calculated. Total AUC of active ATG was shown to be the best predictor for virus reactivation and acute GVHD of grades II to IV or grades III and IV. The optimal total AUC range of active ATG was 100 to 148.5 UE/mL/day. The median time was 14 versus 13 days (P = .184) for neutrophil engraftment and 13 versus 13 days (P = .263) for platelet engraftment in the optimal and non-optimal AUC groups, respectively. The optimal AUC group showed a lower cumulative incidence of cytomegalovirus (CMV) reactivation and persistent CMV viremia than the non-optimal AUC group: 60.6% (95% confidence interval [CI], 48.3%-73.1%) versus 77.1% (95% CI, 64.5%-87.7%; P = .016) and 31.5% (95% CI, 21.2%-45.3%) versus 56.3% (95% CI, 42.9%-70.4%; P = .007), respectively. The cumulative incidence of persistent Epstein-Barr virus (EBV) viremia in the optimal AUC group was significantly lower than the non-optimal total AUC group: 33.1% (95% CI, 22.5%-46.8%) versus 52.6% (95% CI, 39.3%-67.2%; P = .048). However, there was no difference in EBV reactivation (P = .752). Similar outcomes were observed for grade II to IV and grade III and IV acute GVHD between the two groups: 48.6% (95% CI, 36.8%-62.0%) versus 37.0% (95% CI, 24.8%-52.5%; P = .113) and 10.4% (95% CI, 4.8%-21.7%) versus 4.2% (95% CI, 1.0%-15.6%; P = .234, respectively. Relapse, non-relapse mortality, and disease-free survival demonstrated no significant differences between the two groups. But, overall survival at 2 years tended to increase in the optimal AUC group: 75.7% (95% CI, 62.4%-84.8%) versus 57.8% (95% CI, 42.4%-70.4%; P = .061). These data support an optimal active ATG exposure of 110 to 148.5 UE/mL/day in haplo-PBSCT. Individualized dosing of ATG in allo-HCT might reduce the risk of virus reactivation and effectively prevent acute GVHD simultaneously.
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Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco de Sangue Periférico , Animais , Soro Antilinfocitário/uso terapêutico , Infecções por Citomegalovirus/complicações , Infecções por Vírus Epstein-Barr/complicações , Doença Enxerto-Hospedeiro/prevenção & controle , Herpesvirus Humano 4 , Humanos , Recidiva Local de Neoplasia/complicações , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos Prospectivos , Coelhos , Viremia/epidemiologiaRESUMO
In late December 2019, COVID-19 was first identified in Wuhan, China and resulted in a formidable outbreak in provinces and cities in China that became a pandemic. The outbreak likely began as several cases caused by probable zoonotic transmission, followed by human-to-human transmission via droplets or contact with infected bodily fluids or contaminated items. COVID-19 mainly affects the lower respiratory tract and manifests as pneumonia in human, and severely affected patients may have multiple organ dysfunction syndrome. Despite recent progress in vaccine development, the management of multiple organ failure caused by immune injury is mainly supportive. COVID-19 is more contagious than SARS and MERS, although it has a lower mortality rate. The 2019 outbreak of COVID-19 has been classified by the WHO as a Public Health Emergency of International Concern, which has drawn attention to the challenge of the disease and caused questioning of scientific strategies for preventing infection and improving clinical outcomes. This article reviews the latest developments on transmission and clinical management and control of COVID-19 infection.
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COVID-19 , Surtos de Doenças/prevenção & controle , Humanos , Pandemias , SARS-CoV-2 , Desenvolvimento de VacinasRESUMO
Polycyclic aromatic hydrocarbons (PAHs) are hazardous pollutants that are ubiquitous in the environment. Numerous bacteria have evolved to have degrading genes or pathways to degrade PAHs. Stenotrophomonas maltophilia strain W18 was found to be able to degrade PAHs. Including 43 other complete genome sequences of S. maltophilia strains, we performed a comparative genomic analysis of 44 S. maltophilia strains by running OrthoFinder. A KEGG pathway enrichment analysis of environmental and clinical isolates of S. maltophilia revealed that environmental isolates tended to enhance gene functions such as "energy metabolism," "amino acid metabolism," "xenobiotic biodegradation and metabolism," and "folding, sorting, and degradation." The pangenome of the 44 S. maltophilia strains was open, while the core genome was estimated to reach a steady plateau. Based on gene annotations, we inferred that most of the degradation potential came from the core genome of S. maltophilia, while character genes and accessory genes also contributed to the degradation ability of S. maltophilia W18. The genes expression level of core genes, character genes and accessory genes were proved by RT-qPCR experiment, and accessory genes encoding alcohol dehydrogenase were upregulated most compared with genes with similar functions. We performed a credible comparative genomic analysis of S. maltophilia strains. S. maltophilia W18 was set as a model PAH-degrading bacterium of this species in this study, which would provide guidance for understanding and predicting the degradation mechanisms of other PAH-degrading S. maltophilia strains lacking complete genome data or waiting to be determined. IMPORTANCE This study provided the latest comparative genomic analysis on Stenotrophomonas maltophilia strains and focused on analyzing their genomic features that allow them to adapt to natural environments. In this study, we set S. maltophilia W18 as a typical PAH-degrading strain of this species. By discussing the genomic adaptative features of degrading PAH, we can predict genomic adaptative features of other S. maltophilia PAH-degrading strains since the core function of this species is stable. The gene functions of how S. maltophilia environmental isolates are enhanced for adaptation to various natural environments compared with clinical isolates have been revealed. Combined with a pangenome analysis and RT-qPCR results, we have proved that core genes, character genes, and accessory genes are all involved in PAH degradation. Accessory genes encoding alcohol dehydrogenase were upregulated most compared with core and character genes with similar functions, which suggests that PAH metabolization potential might be enhanced by horizontal gene transfer.
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Biodegradação Ambiental , Genoma Bacteriano/genética , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Stenotrophomonas maltophilia/genética , Stenotrophomonas maltophilia/metabolismo , Adaptação Fisiológica/genética , Álcool Desidrogenase/genética , Poluentes Ambientais/metabolismo , Genômica , FilogeniaRESUMO
Accumulating studies had been performed using magnetic resonance imaging (MRI) to understand the neural mechanism of acupuncture therapy for depression. However, inconsistencies remain due to differences in research designs and MRI analytical methods. Therefore, we aim to summarize the current MRI research and provide useful information for further research by identifying papers published in English and Chinese about MRI studies on acupuncture for depression up to November 2020. A total of 22 studies met the inclusion criteria, including 810 depression patients and 416 health controls (HCs). The applied designs of these studies are mainly random control trial and pre-post designs. The MRI analytical methods are mainly (fractional) amplitude of low-frequency fluctuation (fALFF/ALFF) and functional connectivity (FC), whereas a small subset of studies used voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). The most consistent functional MRI (fMRI) results showed increased N-acetylaspartate/creatine (NAA/Cr) ratios, increased ALFF in the right precuneus, decreased ALFF in the inferior frontal gyrus (IFG), and increased FC of the anterior cingulate cortex (ACC). In contrast, no significant neurological changes were identified in any of the DTI or VBM studies. However, clear, reliable conclusions cannot be drawn due to the use of different designs, analytical methods, seed points selected, types of depression, acupuncture points, and so on. Improved report specifications, well-designed studies, consistent analytical methods, and larger sample sizes will enable the field to better elucidate the underlying mechanisms of acupuncture in depressed patients.
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BACKGROUND: Long non-coding RNA (lncRNA) has gradually received widespread attention due to its role in regulating tumor progression. However, in renal cell cancer (RCC), the exact function of lncRNA LINC00671 remains uncertain. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for detecting LINC00671 and miR-221-5p expressions in RCC tissues and cell lines. Western blotting technique was utilized for detecting the expressions of epithelial-mesenchymal transition (EMT)-associated proteins (E-cadherin and N-cadherin) and suppressor of cytokine signaling 1 (SOCS1). The correlation between clinicopathological features and LINC00671 expression was also evaluated. RCC cell multiplication, migration and invasion were measured by CCK-8, EdU and Transwell assays, respectively. The targeted relationships between LINC00671 as well as the SOCS1 3'UTR and miR-221-5p were verified by RNA immunoprecipitation (RIP) and luciferase reporter gene assay. RESULTS: LINC00671 expression in RCC tissues and cells was significantly reduced. Patients with low LINC00671 expression had relatively shorter disease-free survival and overall survival. Moreover, LINC00671 expression was linked to lymph node metastasis, tumor stage, and tumor size. In Caki-1 and 769-P cell lines, LINC00671 overexpression restrained the multiplication, migration, invasion, as well as the EMT process of RCC cells in vitro. In terms of mechanism, miR-221-5p was identified as a target of LINC00671, and LINC00671 could up-regulate SOCS1 by repressing miR-221-5p. CONCLUSION: LINC00671 regulates the miR-221-5p/SOCS1 axis as a tumor suppressor in RCC.
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Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and heterogeneity. Genetic mutations caused by driver genes are important contributors to the formation of the tumor microenvironment. The purpose of this study is to discuss the expression of cancer driver genes in tumor tissues and their clinical value in predicting the prognosis of HCC. Methods: All data were sourced from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) public databases. Differentially expressed and prognostic genes were screened by the expression distribution of the cancer driver genes and their relationship with survival. Candidate genes were subjected to functional enrichment and transcription factor regulatory network. We further constructed a prognostic signature and analyzed the survival outcomes and immune status between different risk groups. Results: Most cancer driver genes are specifically expressed in cancer tissues. Driver genes may influence HCC progression through processes such as transcription, cell cycle, and T-cell receptor-related pathways. Patients in different risk groups had significant survival differences (p < 0.05), and risk scores showed high predictive efficacy (AUC>0.69). Besides, risk subgroups were also associated with multiple immune functions and immune cell content. Conclusion: We confirmed the critical role of cancer driver genes in mediating HCC progression and the immune microenvironment. Risk subgroups contribute to the assessment of prognostic value in different patients and explain the heterogeneity of HCC.
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ABSTRACT: The aim of the study was to analyze the efficacy of posaconazole for the prophylaxis and treatment of invasive fungal diseases (IFDs) in patients with hematological malignancies.In this retrospective observational multi-center study, 762 patients from 25 Chinese hematological centers were enrolled. Inclusion criteria were patients with hematological malignancy or they had undergone hematopoietic stem cell transplantation and received at least 1 dose of posaconazole. The primary endpoints were the observation of breakthrough rates and the clinical efficacy of posaconazole prophylaxis. The secondary endpoint was the efficacy of posaconazole for the treatment of IFDs.Of the 762 enrolled patients, 456 (59.8%) were prescribed posaconazole prophylactically while 243 (31.9%) received posaconazole as an IFD treatment (12 proven, 61 probable, 109 possible, and 61 unclassified IFD cases) for ≥7âdays. The overall IFD breakthrough rate (probable cases) for the ≥4âdays prophylactic treatment (nâ=â445) group was 1.6% (95% Cl: 0.6%-3.2%), with breakthrough rates of 2.6% for acute myeloid leukemia/myelodysplastic syndrome patients undergoing chemotherapy and 2.2% for hematopoietic stem cell transplantation patients. For primary antifungal prophylaxis, the breakthrough rate was 1.9% and for secondary antifungal prophylaxis 0%. The overall effective IFD remission rate of patients treated for ≥7âdays with posaconazole was 56.0% and the effective remission rate of proven/probable/possible IFD cases was 59.3%. The effective remission rate of posaconazole as salvage therapy was 50% (95% CI: 32.4%-67.6%) including 75% (CI: 19.4%-99.4%) for Aspergillus infections.The present retrospective study confirmed posaconazole as IFD prophylaxis and medication for hematological malignancy patients undergoing various treatments in China.
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Antifúngicos/uso terapêutico , Doenças Hematológicas/complicações , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Triazóis/uso terapêutico , Adulto , Feminino , Humanos , Infecções Fúngicas Invasivas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Acupuncture is widely recognized as a potentially effective treatment for stroke rehabilitation. Researchers in this area are actively investigating its therapeutic mechanisms. Magnetic resonance imaging (MRI), as a noninvasive, high anatomical resolution technique, has been employed to investigate neuroplasticity on acupuncture in stroke patients from a system level. However, there is no review on the mechanism of acupuncture treatment for stroke based on MRI. Therefore, we aim to summarize the current evidence about this aspect and provide useful information for future research. After searching PubMed, Web of Science, and Embase databases, 24 human and five animal studies were identified. This review focuses on the evidence on the possible mechanisms underlying mechanisms of acupuncture therapy in treating stroke by regulating brain plasticity. We found that acupuncture reorganizes not only motor-related network, including primary motor cortex (M1), premotor cortex, supplementary motor area (SMA), frontoparietal network (LFPN and RFPN), and sensorimotor network (SMN), as well as default mode network (aDMN and pDMN), but also language-related brain areas including inferior frontal gyrus frontal, temporal, parietal, and occipital lobes, as well as cognition-related brain regions. In addition, acupuncture therapy can modulate the function and structural plasticity of post-stroke, which may be linked to the mechanism effect of acupuncture.
Assuntos
Terapia por Acupuntura/métodos , Encéfalo/diagnóstico por imagem , Plasticidade Neuronal/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Encéfalo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/fisiopatologia , Resultado do TratamentoRESUMO
The 1-year mortality and health consequences of COVID-19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID-19 patients with cancer were compared with 498 non-cancer COVID-19 patients and 498 non-COVID cancer patients. The 1-year all-cause mortality and hospital mortality rates in Cancer COVID-19 Cohort (30% and 20%) were significantly higher than those in COVID-19 Cohort (9% and 8%, both P < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12-month all-cause post-discharge mortality rate in survival discharged Cancer COVID-19 Cohort (8%) was higher than that in COVID-19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID-19 Cohort (23%, 26/114) is similar to that in COVID-19 Cohort (30%, 130/432, P = .13). The 1-year all-cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID-19 patients with cancer showed a high rate of in-hospital mortality and 1-year all-cause mortality, but the 12-month all-cause post-discharge mortality rate in survival discharged cancer COVID-19 patients was similar to that in Cancer Cohort. Comparing to COVID-19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID-19 Cancer Cohort. Different tumor subtypes had different effects on COVID-19. But if cancer patients with COVID-19 manage to survive their COVID-19 infections, then long-term mortality appears to be similar to the cancer patients without COVID-19, and their long-term clinical sequelae were similar to the COVID-19 patients without cancer.