RESUMO

Bipolar nanopores, with asymmetric charge distributions, can induce significant ionic current rectification (ICR) at ultrashort lengths, finding potential applications in nanofluidic devices, energy conversion, and other related fields. Here, with simulations, we investigated the characteristics of ion transport and modulation of the ICR inside bipolar nanopores. With bipolar nanopores of half-positive and half-negative surfaces, the most significant ICR phenomenon appears at various concentrations. In these cases, the ICR ratios are independent of electrolyte types. In other cases where nanopores have oppositely charged surfaces of different lengths, ICR ratios are related to the mobility of anions and cations. The pore length and surface charge density can enhance ICR. As the pore length increases, ICR ratios first increase and then approach their saturation, which is determined by the surface charge density. External surface charges of nanopores can promote the ICR phenomenon mainly due to the enhancement of ion enrichment inside the nanopores by external surface conductance. The effective width of exterior charged surfaces under various conditions is also explored, which is inversely proportional to the pore length and salt concentration and linearly related to the pore diameter, surface charge density, and applied voltage. Our results may provide guidance for the design of bipolar porous membranes.

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Telocytes (TCs) are a type of stromal cell discovered in the various organs of different animals and have many potential functions, including angiogenesis, signalling, and substance transport. However, the TCs have not been detected in the testis or epididymis of Tibetan sheep. This study investigated the position, characteristics, and distribution of TCs in the testis and epididymis of Tibetan sheep using transmission electron microscopy (TEM), toluidine blue staining, immunohistochemistry, and double immunofluorescence to elucidate their possible functions. TEM revealed that TCs were often found near basement membranes and capillaries and were characterised by large nuclei, elongated cytoplasmic protrusions, and many secretory vesicles. We also observed via toluidine staining that TCs were present near basement membrane and interstitial capillaries. Immunohistochemistry and double immunofluorescence revealed the positive expression of CD117, vimentin, platelet derived growth factor receptor α(PDGFRα), PDGFRα + CD117, and PDGFRα + vimentin in TCs. Additionally, we inferred that TCs participates in the formation of the blood-testis and blood-epididymis barriers, as well as in material transport and a stable microenvironment. This study presents the first evidence of the presence of TCs near the basement membrane and blood vessels in the testis and epididymis of Tibetan sheep. These findings provide new insights into the function of TCs in the reproductive systems of plateau animals.

Assuntos

Epididimo , Telócitos , Testículo , Animais , Masculino , Telócitos/metabolismo , Telócitos/citologia , Telócitos/ultraestrutura , Epididimo/metabolismo , Epididimo/citologia , Ovinos , Testículo/metabolismo , Testículo/citologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Microscopia Eletrônica de Transmissão , Tibet , Vimentina/metabolismo , Imuno-Histoquímica , Membrana Basal/metabolismo , Membrana Basal/ultraestrutura

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Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-ß, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC's effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.

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The abundance of molecules on early Earth likely enabled a wide range of prebiotic chemistry, with peptides playing a key role in the development of early life forms and the evolution of metabolic pathways. Among peptides, those with enzyme-like activities occupy a unique position between peptides and enzymes, combining both structural flexibility and catalytic functionality. However, their full potential remains largely untapped. Further exploration of these enzyme-like peptides at the nanoscale could provide valuable insights into modern nanotechnology, biomedicine, and even the origins of life. Hence, this review introduces the groundbreaking concept of "peptide nanozymes (PepNzymes)", which includes single peptides exhibiting enzyme-like activities, peptide-based nanostructures with enzyme-like activities, and peptide-based nanozymes, thus enabling the investigation of biological phenomena at nanoscale dimensions. Through the rational design of enzyme-like peptides or their assembly with nanostructures and nanozymes, researchers have found or created PepNzymes capable of catalyzing a wide range of reactions. By scrutinizing the interactions between the structures and enzyme-like activities of PepNzymes, we have gained valuable insights into the underlying mechanisms governing enzyme-like activities. Generally, PepNzymes play a crucial role in biological processes by facilitating small-scale enzyme-like reactions, speeding up molecular oxidation-reduction, cleavage, and synthesis reactions, leveraging the functional properties of peptides, and creating a stable microenvironment, among other functions. These discoveries make PepNzymes useful for diagnostics, cellular imaging, antimicrobial therapy, tissue engineering, anti-tumor treatments, and more while pointing out opportunities. Overall, this research provides a significant journey of PepNzymes' potential in various biomedical applications, pushing them towards new advancements.

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Trauma is an important cause of death in young- and middle-aged people. Trauma is comprehensive and includes many surgical specialties, and the surgical techniques of these specialties have long been mature. To reduce the mortality and disability rate of trauma patients, it is necessary to improve trauma management. Trauma has attracted attention in China and trauma treatment and care developed rapidly in recent years. To decrease traumatic mortality and disability rates, our team is committed to building an efficient trauma system in Shaanxi province and has successfully developed a trauma limb salvage map to address the high rates of amputation and disability in patients with limb injuries. This article elaborates on the construction experience of a trauma limb salvage map and its application details in Shaanxi province of China.

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Background: Bone metastases of lung cancer (BMLC) severely diminish patients' quality of life due to bone-related events, and the lack of clear guidelines globally regarding medical and surgical treatment significantly reduces patient survival. While knowledge about BMLC has grown exponentially over the past two decades, a comprehensive and objective bibliometric analysis remains absent. Methods: A comprehensive bibliometric analysis was conducted on relevant literature on BMLC extracted from the Web of Science database from 2004 to 2023 by Biblioshiny, VOSviewer, Scimago Graphica, CiteSpace, and Microsoft Office Excel Professional Plus 2016 software. 936 papers related to BMLC were extracted from the Web of Science Core Collection (WoSCC). The number of publications, countries, institutions, global collaborations, authors, journals, keywords, thematic trends, and cited references were then visualized. Finally, the research status and development direction in the last 20 years were analyzed. Results: This study included a total of 936 papers on BMLC from 2004 to 2023. There has been a steady increase in global publications each year, peaking in 2021. China had the highest number of publications, followed by Japan and the United States. Additionally, China had the most citations with an H-index of 35, while the US followed with an H-index of 34, highlighting their significant contributions to the field. "Frontiers in Oncology" had the highest number of publications. CiteSpace analysis identified "lung cancer," "bone metastasis," and "survival" as the top high-frequency keywords, encapsulating the core research focus. Keyword clustering analysis revealed six main clusters representing the primary research directions. Burst analysis of keywords showed that "skeletal complications" had the highest burst intensity from 2005 to 2013, while recent research trends include "immunotherapy" and "denosumab," with bursts from 2021 to 2023. Trend topic analysis indicated that "non-small cell lung cancer," "immunotherapy," and "immune checkpoint inhibitors" represent the cutting-edge research directions in this field. Conclusion: This article reveals the current status and trend of research on BMLC, which is increasing worldwide. China and the United States have contributed the most, but international cooperative research on BMLC should be strengthened. The pathogenesis, early prevention, and individualized treatment of BMLC need to be strengthened for further study, and immunotherapy is the next hotspot of lung cancer bone metastasis research.

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In recent years, with the continuous development of molecular immunology, immune checkpoint inhibitors (ICIs) have also been widely used in the treatment of gastric cancer, but they still face some challenges: The first is that only some people can benefit, the second is the treatment-related adverse events (TRAEs) that occur during treatment, and the third is the emergence of varying degrees of drug resistance with long-term use. How to overcome these challenges, combined therapy based on ICIs has become one of the important strategies. This article summarizes the clinical application of ICIs combined with chemotherapy, targeted therapy, radiotherapy, photodynamic therapy, thermotherapy, immune adjuvant, and dual immunotherapy and discusses the mechanism, and also summarizes the advantages and disadvantages of the current combination modalities and the potential research value. The aim of this study is to provide more and more optimized combination regimen for ICI combined therapy in patients with advanced gastric cancer and to provide reference for clinical and scientific research.

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Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT­PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter­EC adhesion proteins (zona occludens­1, connexin 43 and Vascular endothelial­Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl­CoA synthase long­chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter­EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.

Assuntos

Permeabilidade Capilar , Ferroptose , Osteoartrite , Proteína rhoA de Ligação ao GTP , Proteína rhoA de Ligação ao GTP/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Animais , Humanos , Camundongos , Masculino , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Camundongos Endogâmicos C57BL

RESUMO

Osteoarthritis (OA) is a chronic degenerative disease characterized by subchondral osteosclerosis, mainly due to osteoblast activity. This research investigates the function of Sik1, a member of the AMP-activated protein kinase family, in OA. Proteomic analysis was conducted on clinical samples from 30 OA patients, revealing a negative correlation between Sik1 expression and OA. In vitro experiments utilized BMSCs to examine the effect of Sik1 on osteogenic differentiation. BMSCs were cultured and induced toward osteogenesis with specific media. Sik1 overexpression was achieved through lentiviral transfection, followed by analysis of osteogenesis-associated proteins using Western blotting, RT-qPCR, and alkaline phosphate staining. In vivo experiments involved destabilizing the medial meniscus in mice to establish an OA model, assessing the therapeutic potential of Sik1. The CT scans and histological staining were used to analyze subchondral bone alterations and cartilage damage. The findings show that Sik1 downregulation correlates with advanced OA and heightened osteogenic differentiation in BMSCs. Sik1 overexpression inhibits osteogenesis-related markers in vitro and reduces cartilage damage and subchondral osteosclerosis in vivo. Mechanistically, Sik1 modulates osteogenesis and subchondral bone changes through Runx2 activity regulation. The research emphasizes Sik1 as a promising target for treating OA, suggesting its involvement in controlling bone formation and changes in the subchondral osteosclerosis.

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ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear. AIM OF THE STUDY: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism. MATERIALS AND METHODS: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases. RESULTS: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone. CONCLUSION: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway.

Assuntos

Artemisia , Simulação de Acoplamento Molecular , Extratos Vegetais , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Artemisia/química , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Masculino , Transdução de Sinais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fosfatidilinositol 3-Quinases/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Etanol/química , Linhagem Celular , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Substâncias Protetoras/farmacologia , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/tratamento farmacológico , Humanos

RESUMO

Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.

Assuntos

Ácidos e Sais Biliares , Neoplasias do Colo , Inulina , Neoplasias Pulmonares , Rifaximina , Inulina/farmacologia , Animais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Ácidos e Sais Biliares/metabolismo , Rifaximina/farmacologia , Rifaximina/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Linhagem Celular Tumoral , Masculino , Camundongos Endogâmicos BALB C

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Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adipose-liver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and FMT. Understanding the immunological mechanisms underlying in SLD is crucial for advancing clinical therapeutic strategies.

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Due to rapid homogenization in habitat types as a result of urbanization, some urban birds adapt their nesting strategies to changes in local habitat characteristics. Bird nesting decisions might have been mainly linked to resource constraints and ensuring reproductive success. In this study, we examined patterns of nesting behavior by spotted doves (Spilopelia chinensis) in a rapidly urbanizing area of Nanchang, China using ArcGIS 10.8, satellite tracking, camera traps, and field survey. To explore the mechanisms underlying nesting behavior in urban habitats, we assessed the correlations between nest reuse and reproductive success, and between nest reuse and nest predation. From December 2018 to December 2021, a total of 302 breeding nests were surveyed. The results revealed that the nest reuse rate was 38.08% (n = 115). Nests closer to trunk, with lower nest position and higher large-scale urbanization score tended to have higher reuse rate. In addition, nests with the higher the nest height and percent of canopy cover, and the lower small-scale urbanization score were more likely to reproduce successfully, and the reused nests also reproduce more successfully. The reproductive success associated with nest reuse was significantly higher than that associated with new nests (χ 2 = 8.461, p = .004). High degree of urbanization promoted nest reuse of spotted doves (large-scale urbanization score, z = 2.094, p = .036), which apparently enhanced their reproductive success (nest reuse, z = 2.737, p = .006). In conclusion, a nest structure with good permeability is the material basis for the nest reuse in spotted dove, while the relatively low risk of predation in urban habitat and the scarcity of nest site resources due to urbanization increase the tendency of birds to reuse old nests, which is associated with their reproductive success and evolutionary fitness.

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At the 3' end of the C2 gene in the mammalian TRB locus, a distinct reverse TRBV30 gene (named TRBV31 in mice) has been conserved throughout evolution. In the fully annotated TRB locus of 14 mammals (including six orders), we observed noteworthy variations in the localization and quality of the reverse V30 genes and Recombination Signal Sequences (RSSs) in the gene trees of 13 mammals. Conversely, the forward V29 genes and RSSs were generally consistent with the species tree of their corresponding species. This finding suggested that the evolution of the reverse V30 gene was not synchronous and likely played a crucial role in regulating adaptive immune responses. To further investigate this possibility, we utilized single-cell TCR sequencing (scTCR-seq) and high-throughput sequencing (HTS) to analyze TCRß CDR3 repertoires from both central and peripheral tissues of Primates (Homo sapiens and Macaca mulatta), Rodentia (Mus musculus: BALB/c, C57BL/6, and Kunming mice), Artiodactyla (Bos taurus and Bubalus bubalis), and Chiroptera (Rhinolophus affinis and Hipposideros armige). Our investigation revealed several novel observations: (1) The reverse V30 gene exhibits classical rearrangement patterns adhering to the '12/23 rule' and the 'D-J rearrangement preceding the V-(D-J) rearrangement'. This results in the formation of rearranged V30-D2J2, V30-D1J1, and V30-D1J2. However, we also identified 'special rearrangement patterns' wherein V30-D rearrangement preceding D-J rearrangement, giving rise to rearranged V30-D2-J1 and forward Vx-D2-J. (2) Compared to the 'deletional rearrangement' (looping out) of forward V1-V29 genes, the reverse V30 gene exhibits preferential utilization with 'inversional rearrangement'. This may be attributed to the shorter distance between the V30 gene and D gene and the 'inversional rearrangement' modes. In summary, in the mammalian TRB locus, the reverse V30 gene has been uniquely preserved throughout evolution and preferentially utilized in V(D)J recombination, potentially serving a significant role in adaptive immunity. These results will pave the way for novel and specialized research into the mechanisms, efficiency, and function of V(D)J recombination in mammals.

Assuntos

Evolução Molecular , Mamíferos , Animais , Mamíferos/genética , Humanos , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala , Camundongos

RESUMO

The spine is a common site for metastatic tumors, with 5%-10% of patients developing epidural spinal cord compression (ESCC), which significantly reduces their quality of life and accelerates the process of death. When total en-bloc spondylectomy (TES) radical surgery does not achieve the desired tumor control, palliative care remains the primary treatment option. Traditional laminar decompression or partial tumor resection can only relieve local compression. Although the surgical trauma and complications are less, these methods cannot effectively address tumor recurrence and secondary compression. Therefore, separation surgery combined with radiofrequency ablation and bone cement strengthening was used to treat thoracolumbar metastatic tumors, aiming to achieve good clinical results. In this protocol, the steps and key points of separation surgery combined with radiofrequency ablation and bone cement reinforcement for thoracolumbar metastatic tumors are introduced in detail. Meanwhile, the clinical data of 67 cases of thoracolumbar metastatic tumors in our hospital meeting the inclusion criteria were retrospectively analyzed. Different treatment methods divided the patients into two groups: separation surgery combined with radiofrequency ablation and bone cement strengthening (group A, 33 cases) and the radiotherapy group (group B, 34 cases). All patients were evaluated using improved Tokuhashi, Tomita, SINS, and ESCC scores before treatment. VAS score, Frankel grading, and Karnofsky scores during different periods of the two treatments were compared to assess the clinical outcomes. Studies have shown that separation surgery combined with radiofrequency ablation and bone cement strengthening can significantly reduce pain, promote neurological function recovery, enhance mobility, and improve quality of life in treating thoracolumbar metastatic tumors.

Assuntos

Cimentos Ósseos , Vértebras Lombares , Ablação por Radiofrequência , Neoplasias da Coluna Vertebral , Vértebras Torácicas , Humanos , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/secundário , Vértebras Torácicas/cirurgia , Vértebras Lombares/cirurgia , Ablação por Radiofrequência/métodos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Retrospectivos

RESUMO

CRISPR/Cas-based diagnostics (CRISPR-Dx) face challenges, including difficulty in detecting ultrashort nucleotides, preamplification dependency, cross-contamination, insufficiency in on-pot detection paradigms, and inconvenience in detecting non-nucleic acid targets. This forum outlines the advances in engineered CRISPR RNA (crRNA) that address the aforementioned problems, highlighting challenges, opportunities, and future directions.

RESUMO

Previous studies have found that the peripheral immune environment is closely related to the occurrence and development of intracranial aneurysms. However, it remains unclear how the metabolism of peripheral blood mononuclear cells (PBMCs) and the composition of polymorphonuclear leukocytes (PMNs) changes in the process of intracranial aneurysm rupture. This study utilized cytometry by time of flight technology to conduct single-cell profiling analysis of PBMCs and PMNs from 72 patients with IAs. By comparing the expression differences of key metabolic enzymes in PBMCs between patients with ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms, we found that most PBMCs subsets from RIA group showed upregulation of rate-limiting enzymes related to the glycolytic pathway. By comparing the composition of PMNs, it was found that the proinflammatory CD101+HLA DR+ subsets were increased in the RIA group, accompanied by a decrease in the anti-inflammatory polymorphonuclear myeloid-derived suppressor cells. In conclusion, this study showed the changes in the peripheral immune profile of RIAs, which is helpful for our understanding of the mechanisms underlying peripheral changes and provides a direction for future related research.

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Carotid atherosclerosis is a major cause of stroke. Hemodynamic forces, such as shear stress and oscillatory shear, play an important role in the initiation and progression of atherosclerosis. The alteration of the immune microenvironment is the fundamental pathological mechanism by which diverse external environmental factors impact the formation and progression of plaques. However, Current research on the relationship between hemodynamics and immunity in atherosclerosis still lack of comprehensive understanding. In this study, we combined computational fluid dynamics (CFD) and Mass cytometry (CyTOF) technologies to explore the changes in the immune microenvironment within plaques under different hemodynamic conditions. Our results indicated that neutrophils were enriched in adverse flow environments. M2-like CD163+CD86+ macrophages were predominantly enriched in high WSS and low OSI environments, while CD163-CD14+ macrophages were enriched in low WSS and high OSI environments. Functional analysis further revealed T cell pro-inflammatory activation and dysregulation in modulation, along with an imbalance in M1-like/M2-like macrophages, suggesting their potential involvement in the progression of atherosclerotic lesions mediated by adverse flow patterns. Our study elucidated the potential mechanisms by which hemodynamics regulated the immune microenvironment within plaques, providing intervention targets for future precision therapies.

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Epidemic forecasts are only as good as the accuracy of epidemic measurements. Is epidemic data, particularly COVID-19 epidemic data, clean, and devoid of noise? The complexity and variability inherent in data collection and reporting suggest otherwise. While we cannot evaluate the integrity of the COVID-19 epidemic data in a holistic fashion, we can assess the data for the presence of reporting delays. In our work, through the analysis of the first COVID-19 wave, we find substantial reporting delays in the published epidemic data. Motivated by the desire to enhance epidemic forecasts, we develop a statistical framework to detect, uncover, and remove reporting delays in the infectious, recovered, and deceased epidemic time series. Using our framework, we expose and analyze reporting delays in eight regions significantly affected by the first COVID-19 wave. Further, we demonstrate that removing reporting delays from epidemic data by using our statistical framework may decrease the error in epidemic forecasts. While our statistical framework can be used in combination with any epidemic forecast method that intakes infectious, recovered, and deceased data, to make a basic assessment, we employed the classical SIRD epidemic model. Our results indicate that the removal of reporting delays from the epidemic data may decrease the forecast error by up to 50%. We anticipate that our framework will be indispensable in the analysis of novel COVID-19 strains and other existing or novel infectious diseases.