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Small nucleolar RNAs (snoRNAs) were previously regarded as a class of functionally conserved housekeeping genes, primarily involved in the regulation of ribosome biogenesis by ribosomal RNA (rRNA) modification. However, some of them are involved in several biological processes via complex molecular mechanisms. DNA damage response (DDR) is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases. It has recently been revealed that snoRNAs are involved in DDR at multiple levels, indicating their relevant theoretical and clinical significance in this field. The present review systematically addresses four main points, including the biosynthesis and classification of snoRNAs, the mechanisms through which snoRNAs regulate target molecules, snoRNAs in the process of DDR, and the significance of snoRNA in disease diagnosis and treatment. It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.
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Dano ao DNA , RNA Nucleolar Pequeno , RNA Nucleolar Pequeno/genética , Dano ao DNA/fisiologia , Humanos , Instabilidade GenômicaRESUMO
Breast cancer (BC) is the most common tumor worldwide and requires crucial molecular typing for treatment and prognosis assessment. Currently, approaches like pathological staining, immunohistochemistry (IHC), and immunofluorescence (IF) face limitations due to the low signal-to-background ratio (SBR) and high tumor heterogeneity, resulting in a high misdiagnosis rate. Fluorescent assay in the second near-infrared region (NIR-II, 1000-1700 nm) exhibits ultrahigh SBR owing to diminished scattering and tissue autofluorescence. Here, we present a NIR-II strategy for accurate BC molecular typing and three-dimensional (3D) visualization based on the atomically precise fluorescent Au24Pr1 clusters. Single-atom Pr doping results in 3.9-fold fluorescence enhancement and long-term photostability. The Au24Pr1 clusters possess high fluorescence centered at â¼1100 nm and the SBR on pathological section diagnosis was 4 times higher than that of NIR-I imaging. This enables high spatial resolution 3D visualization of biopsy specimens, which can surmount tissue heterogeneity for clinical diagnosis of BC.
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In the event of a nuclear or radiation accident, rapid identification is required for those who exposed to potentially lethal dose irradiation. However, existing techniques are not adequate for the classification of lethal injury. Several studies have explored the potential of miRNAs as biomarkers for ionizing radiation injury, however, there are few miRNAs with specific expression for lethal radiation injury. Therefore, the aim of this study was to screen and validate the possibility of serum miRNAs as biomarkers of lethal radiation injury. We found the specific expression of mmu-miR-374c-5p / mmu-miR-194-5p on first day and mmu-miR-192-5p / mmu-miR-223-3p on third day in the mouse serum only under 10Gy irradiation by miRNA sequencing and all significantly correlated with lymphocyte counts by Pearson's correlation analysis. In addition, it was found that among the 4 candidate serum miRNAs, only highly-expressed mmu-miR-192-5p in mouse serum irradiated at lethal doses was returned to sham-like expression levels at 3 days post-irradiation with amifostine pretreatment and closely correlated with survival rate. We demonstrated for the first time that mmu-miR-192-5p screened from lethally irradiated mice sera can be used as a potential biomarker for lethal irradiation injury, which will be helpful to improve efficiency of medical treatment to minimize casualties after a large-scale nuclear accident.
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We propose to improve the solar energy utilization by using InGaN inclined nanowire array photocathodes. We first study vertical nanowire array. On the basis of vertical nanowire array, we study inclined nanowires by changing the inclination angle of nanowires. The inclined nanowires exhibit higher quantum efficiency at larger period and larger inclination angle. However, the infinite expansion of period will cause its performance to degrade. The quantum efficiency of inclined nanowires with a period of 175 nm and an inclination angle of 5.35° is as high as 80.2% when the incident light angle is irradiated at 5°. In addition, applying an electric field can improve the collection efficiency of inclined nanowires and help them maintain a high collection efficiency over a longer wavelength range. The design principles proposed in this work will provide a theoretical reference for the performance improvement of InGaN photocathodes.
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A combination of morphological traits and DNA data (COI and 28S rRNA partial sequences) was used to study the genus Mongoloniscus Verhoeff, 1930 from China. Four new species are described: M.crenatus Jiang, Li & Huang, sp. nov., M.orientalis Jiang, Li & Huang, sp. nov., M.polyacanthum Jiang, Li & Huang, sp. nov., and M.parvus Jiang, Li & Huang, sp. nov. Following an in-depth examination of the Mongoloniscus species, Lucasioidesvannamei (Arcangeli, 1927), comb. nov. (from Mongoloniscus) is proposed, and M.chevronus Yang & An, 2021, syn. nov. is synonymized with Koreoniscusracovitzai (Arcangeli, 1927). A restrictive criterion for recognizing the genus Mongoloniscus is also provided in the present study.
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Radiotherapy is essential for treating colorectal cancer (CRC), especially in advanced rectal cancer. However, the low radiosensitivity of CRC cells greatly limits radiotherapy efficacy. Small nucleolar RNAs (snoRNAs) are a class of noncoding RNA that primarily direct post-transcriptional modifications of ribosomal RNAs (rRNAs), small nuclear RNAs (snRNAs), and other cellular RNAs. While snoRNAs are involved in tumor progression and chemoresistance, their association with radiosensitivity remains largely unknown. Herein, SNORA28 is shown highly expressed in CRC and is positively associated with poor prognosis. Furthermore, SNORA28 overexpression enhances the growth and radioresistance of CRC cells in vitro and in vivo. Mechanistically, SNORA28 acts as a molecular decoy that recruits bromodomain-containing protein 4 (BRD4), which increases the level of H3K9 acetylation at the LIFR promoter region. This stimulates LIFR transcription, which in turn triggers the JAK1/STAT3 pathway, enhancing the proliferation and radioresistance of CRC cells. Overall, these results highlight the ability of snoRNAs to regulate radiosensitivity in tumor cells and affect histone acetylation modification in the promoter region of target genes, thus broadening the current knowledge of snoRNA biological functions and the mechanism underlying target gene regulation.
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BACKGROUND AND AIMS: As global life expectancy rises and gastrointestinal tumor incidence increases, more elderly patients are undergoing endoscopic submucosal dissection (ESD) for tumor treatment. The current situation highlights the importance of sarcopenia assessment before ESD. This systematic review and meta-analysis aim to assess sarcopenia's role in predicting post-ESD adverse outcomes in the elderly. METHODS: We conducted a systematic review and meta-analysis to investigate the impact of sarcopenia on the prognosis of elderly patients undergoing ESD treatment. A comprehensive search was conducted across three databases (PubMed, Embase, Web of Science). We were using NEWCASTLE-OTTAWA ASSESSMENT SCALE for risk of bias assessment. The data were synthesized using Review Manager 5.3. RESULTS: A total of 9 reports were identified, analyzing 7 indicators, with a combined sample size of 6044. Through a series of analyses, we have derived several highly credible research findings: the overall OR and 95% CI for gastric and colorectal post-ESD perforation between sarcopenia and nonsarcopenia groups were 1.34 [0.92, 1.97], for CTCAE grade > 2 was 2.65 [1.45, 4.82], for upper gastrointestinal post-ESD pneumonia were 1.97 [1.30, 2.99], and for gastric post-ESD mortality within 5 years were 2.96 [1.33, 6.58]. CONCLUSIONS: Sarcopenia is a risk factor for increased incidence of complications (CTCAE > 2) after undergoing gastric and colorectal ESD, increased pneumonia rates, and higher mortality rates within five years following gastric ESD treatment in elderly patients. However, sarcopenia does not lead to an increased perforation rate in elderly patients undergoing gastric and colorectal ESD treatments. Registration and protocol: The protocol for this study was registered on the Open Science Framework in 2024 https://doi.org/10.17605/OSF.IO/7B2CZ . We also conducted pre-registration on PROSPERO (CRD42024532547).
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Objective: It's crucial to identify an easily detectable biomarker that is specific to radiation injury in order to effectively classify injured individuals in the early stage in large-scale nuclear accidents. Methods: C57BL/6J mice were subjected to whole-body and partial-body γ irradiation, as well as whole-body X-ray irradiation to explore the response of serum sSelectin-L to radiation injury. Then, it was compared with its response to lipopolysaccharide-induced acute infection and doxorubicin-induced DNA damage to study the specificity of sSelectin-L response to radiation. Furthermore, it was further evaluated in serum samples from nasopharyngeal carcinoma patients before and after radiotherapy. Simulated rescue experiments using Amifostine or bone marrow transplantation were conducted in mice with acute radiation syndrome to determine the potential for establishing sSelectin-L as a prognostic marker. The levels of sSelectin-L were dynamically measured using the ELISA method. Results: Selectin-L is mainly expressed in hematopoietic tissues and lymphatic tissues. Mouse sSelectin-L showed a dose-dependent decrease from 1 day after irradiation and exhibited a positive correlation with lymphocyte counts. Furthermore, the level of sSelectin-L reflected the degree of radiation injury in partial-body irradiation mice and in nasopharyngeal carcinoma patients. sSelectin-L was closely related to the total dose of γ or X ray. There was no significant change in the sSelectin-L levels in mice intraperitoneal injected with lipopolysaccharide or doxorubicin. The sSelectin-L was decreased slower and recovered faster than lymphocyte count in acute radiation syndrome mice treated with Amifostine or bone marrow transplantation. Conclusions: Our study shows that sSelectin-L has the potential to be an early biomarker to classify injured individuals after radiation accidents, and to be a prognostic indicator of successful rescue of radiation victims.
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Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4+ T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4+ subset polarization in a paracrine mode, in which TGFß and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228.
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Explosions in the battlefield can result in brain damage. Research on the effects of shock waves on brain tissue mainly focuses on the effects of single-orientation blast waves, while there have been few studies on the dynamic response of the human brain to directional explosions in different planes, multi-point explosions and repetitive explosions. Therefore, the brain tissue response and the intracranial pressure (ICP) caused by different blast loadings were numerically simulated using the CONWEP method. In the study of the blast in different directions, the lateral explosion blast wave was found to cause greater ICP than did blasts from other directions. When multi-point explosions occurred in the sagittal plane simultaneously, the ICP in the temporal lobe increased by 37.8 % and the ICP in the parietal lobe decreased by 17.6 %. When multi-point explosions occurred in the horizontal plane, the ICP in the frontal lobe increased by 61.8 % and the ICP in the temporal lobe increased by 12.2 %. In a study of repetitive explosions, the maximum ICP of the second blast increased by 40.6 % over that of the first blast, and that of the third blast increased by 61.2 % over that of the second blast. The ICP on the brain tissue from repetitive blasts can exceed 200 % of that of a single explosion blast wave.
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Traumatismos por Explosões , Lesões Encefálicas , Explosões , Pressão Intracraniana , Humanos , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/patologia , Traumatismos por Explosões/fisiopatologia , Traumatismos por Explosões/patologia , Encéfalo/fisiopatologia , Encéfalo/patologiaRESUMO
Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.
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Ouro , Nanopartículas Metálicas , Ouro/toxicidade , Ouro/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/químicaRESUMO
Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.
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Terapia de Salvação , Transplante Haploidêntico , Humanos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Transplante Haploidêntico/métodos , Adolescente , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Rejeição de Enxerto/etiologia , Adulto Jovem , Transplante Homólogo/métodosRESUMO
BACKGROUND: Neoadjuvant chemotherapy, used to shrink tumors before surgery, is increasingly applied in clinical practice. However, retrospective studies indicate that it may increase sarcopenia rates and consequently result in an elevated occurrence rate of postoperative severe complications such as severe surgical incision infection, severe respiratory failure, and severe postoperative hemorrhage, especially in the elderly population. Currently, no systematic analysis examines the association between neoadjuvant chemotherapy and sarcopenia. This study aims to fill this gap with a comprehensive meta-analysis focused on this critical aspect of the field. METHODS: A systematic literature search was conducted in the PubMed and Web of Science databases from their inception to January 2024. The included studies encompassed patients who received neoadjuvant chemotherapy and underwent computed tomography (CT) scans both before and after treatment to calculate skeletal muscle index (SMI) or categorize them for the presence of sarcopenia. The determination of sarcopenia status was based on well-established and validated threshold criteria. Data extraction was performed independently by two reviewers. A meta-analysis was employed to estimate the pooled odds ratio (OR) and its corresponding 95% confidence interval (95% CI) to assess the risk of neoadjuvant chemotherapy-induced muscle reduction. RESULTS: In the 14 studies with complete categorical variable data, comprising 1853 patients, 773 patients were identified as having sarcopenia before neoadjuvant treatment and 941 patients had sarcopenia after neoadjuvant therapy. The OR and its 95% CI was calculated as 1.51 [1.31, 1.73]. Among these, 719 patients had digestive system cancer, with 357 patients having sarcopenia before neoadjuvant treatment and 447 patients after, resulting in an OR of 1.74 [1.40, 2.17]. In the remaining 1134 patients with non-digestive system cancers, 416 were identified as having sarcopenia before neoadjuvant treatment, and 494 patients had sarcopenia after, with an OR of 1.37 [1.15, 1.63]. Additionally, in seven studies with complete continuous variable data, including 1228 patients, the mean difference in the change of SMI before and after neoadjuvant treatment was - 1.13 [- 1.65, - 0.62]. After excluding low-quality small-sample studies with fewer than 50 patients, the same trend was observed in the analysis. CONCLUSION: The risk of muscle reduction significantly increases in cancer patients after neoadjuvant chemotherapy and digestive system cancers tend to have a higher risk of developing sarcopenia post-treatment compared to non-digestive system cancers.
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Terapia Neoadjuvante , Neoplasias , Sarcopenia , Sarcopenia/induzido quimicamente , Humanos , Terapia Neoadjuvante/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Quimioterapia Adjuvante/efeitos adversos , Complicações Pós-Operatórias , Músculo Esquelético/patologiaRESUMO
Petroleum, as the "lifeblood" of industrial development, is the important energy source and raw material. The selective transformation of petroleum into high-end chemicals is of great significance, but still exists enormous challenges. Single-atom catalysts (SACs) with 100% atom utilization and homogeneous active sites, promise a broad application in petrochemical processes. Herein, the research systematically summarizes the recent research progress of SACs in petrochemical catalytic reaction, proposes the role of structural design of SACs in enhancing catalytic performance, elucidates the catalytic reaction mechanisms of SACs in the conversion of petrochemical processes, and reveals the high activity origins of SACs at the atomic scale. Finally, the key challenges are summarized and an outlook on the design, identification of active sites, and the appropriate application of artificial intelligence technology is provided for achieving scale-up application of SACs in petrochemical process.
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Gold nanoclusters (Au NCs) exhibit broad fluorescent spectra from visible to near-infrared regions and good enzyme-mimicking catalytic activities. Combined with excellent stability and exceptional biocompatibility, the Au NCs have been widely exploited in biomedicine such as biocatalysis and bioimaging. Especially, the long fluorescence lifetime and large Stokes shift attribute Au NCs to good probes for fluorescence sensing and biological detection. In this review, we systematically summarized the molecular structure and fluorescence properties of Au NCs and highlighted the advances in fluorescence sensing and biological detection. The Au NCs display high sensitivity and specificity in detecting iodine ions, metal ions, and reactive oxygen species, as well as certain diseases based on the fluorescence activities of Au NCs. We also proposed several points to improve the practicability and accelerate the clinical translation of the Au NCs.
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Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The incidence of PTC has increased annually worldwide. Thus, PTC diagnosis and treatment attract more attention. Noncoding RNAs (lncRNAs) play crucial roles in PTC progression and act as prognostic biomarkers. Moreover, microRNAs (miRNAs) and epithelial-mesenchymal transition (EMT)-associated proteins have potential biomarkers for diagnosing and treating PTC. However, the correlation of lncRNAs with miRNAs and EMT-associated proteins needs further clarification. The present review highlights the recent advances of lncRNAs in PTC. We significantly summarized the two molecular regulatory mechanisms in PTC progress, including lncRNAs-miRNAs-protein signaling axes and lncRNAs-EMT pathways. This review will help our understanding of the association between lncRNAs and PTC and may assist us in evaluating the prognosis for PTC patients. Taken together, targeting the lncRNAs regulatory network has promising applications in diagnosing and treating PTC.
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Aseptic loosening (AL) is considered a significant cause of prosthesis revision after arthroplasty and a crucial factor in the longevity of an artificial joint prosthesis. The development of AL is primarily attributed to a series of biological reactions, such as peri-prosthetic osteolysis (PPO) induced by wear particles around the prosthesis. Chronic inflammation of the peri-prosthetic border tissue and hyperactivation of osteoclasts are key factors in this process, which are induced by metallic wear particles like Ti particles (TiPs). In our in vitro study, we observed that TiPs significantly enhanced the expression of inflammation-related genes, including COX-2, IL-1ß and IL-6. Through screening a traditional Chinese medicine database, we identified byakangelicol, a traditional Chinese medicine molecule that targets COX-2. Our results demonstrated that byakangelicol effectively inhibited TiPs-stimulated osteoclast activation. Mechanistically, we found that byakangelicol suppressed the expression of COX-2 and related pro-inflammatory factors by modulating macrophage polarization status and NF-κB signaling pathway. The in vivo results also demonstrated that byakangelicol effectively inhibited the expression of inflammation-related factors, thereby significantly alleviating TiPs-induced cranial osteolysis. These findings suggested that byakangelicol could potentially be a promising therapeutic approach for preventing PPO.
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Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, and represents a severe threat to the life and health of individuals. Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) as critical regulatory gene in cancer development. Small Cajal body-specific RNAs (scaRNAs), a subtype of snoRNAs, are named for their subcellular localization within Cajal bodies. SCARNA12, which located at the intronic region of PHB2 in chromosome 12p13.31 with 270 nucleotides (nt) in length. It has been reported function as a diagnostic marker for cervical cancer. However, its biological functions and molecular mechanisms in CRC have yet to be elucidated. In this study, bioinformatics analysis revealed that SCARNA12 was highly expressed in CRC and positively correlated with poor prognosis in CRC patients. Additionally, SCARNA12 showed upregulated expression in CRC cell lines and clinical CRC tissue samples. Moreover, SCARNA12 overexpression in SW620 cells accelerated cell proliferation, suppressed the apoptosis rate, and enhanced tumorigenesis in vivo. The knockdown of SCARNA12 expression in HCT116 and HT29 cells resulted in contrasting effects. The functioning of SCARNA12 is mechanically independent of its host gene PHB2. Notably, the overexpression of SCARNA12 activated PI3K/AKT pathway in SW620 cells, and the malignancy degree of CRC cells was attenuated after treatment with MK2206 (a specific AKT inhibitor). Our findings demonstrated that SCARNA12 plays an oncogenic role in CRC progression and can be used as a potential diagnostic biomarker for CRC.
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INTRODUCTION: Thymoma is a common mediastinal tumor, but few studies have been performed in thymoma patients 80 years or older. This study aimed to analyze the clinical features, treatment modalities, and survival outcomes of thymoma patients at least 80 years old and compare these features to those of patients younger than 80 years old. METHOD: Data from thymoma patients in the Surveillance, Epidemiology and End Results database between 2000 and 2019 were selected. Clinical features, treatment modalities of the two age groups were compared. Survival rates were calculated by the Kaplan-Meier method and the log-rank test was used to compare survival rates between two groups. Propensity score matching was used based on whether surgery was performed. Univariate and multivariate Cox proportional-hazards regression analyses were performed to identify independent prognostic factors. RESULTS: Compared with the younger patients, the patients aged 80 years or older had a similar distribution of Masaoka-Koga tumor stage, a higher proportion of type A thymoma, and a lower recurrence rate in the early stage. In elderly patients after propensity score matching, the overall survival and cancer-specific survival were better in the surgery group with complete resection and compared with patients of different ages, elderly patients showed similar benefit from surgery as younger patients were observed. CONCLUSION: In thymoma patients aged 80 years or older, surgery still plays an important role in survival outcome. Compared with younger patients, older patients have unique clinical features.