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Técnicas Cosméticas , Rejuvenecimiento , Envejecimiento de la Piel , Terapia por Ultrasonido , Humanos , Envejecimiento de la Piel/efectos de la radiación , Terapia por Ultrasonido/métodos , Terapia por Ultrasonido/efectos adversos , Técnicas Cosméticas/efectos adversos , Resultado del Tratamiento , Piel/efectos de la radiaciónRESUMEN
BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a rare pathological histotype in ovarian cancer, while the survival rate of advanced OCCC (Stage III-IV) is substantially lower than that of the advanced serous ovarian cancer (OSC), which is the most common histotype. The goal of this study was to identify high-risk OCCC by comparing OSC and OCCC, with investigating potential risk and prognosis markers. METHODS: Patients diagnosed with ovarian cancer from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) Program. Logistic and Cox regression models were used to identify risk and prognostic factors in high-risk OCCC patients. Cancer-specific survival (CSS) and overall survival (OS) were assessed using Kaplan-Meier curves. Furthermore, Cox analysis was employed to build a nomogram model. The performance evaluation results were displayed using the C-index, calibration plots, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Immunohistochemically approach was used to identify the expression of the novel target (GPC3). RESULTS: In the Cox analysis for advanced OCCC, age (45-65 years), tumor numbers (total number of in situ/malignant tumors for patient), T3-stage, bilateral tumors, and liver metastases could be defined as prognostic variables. Nomogram showed good predictive power and clinical practicality. Compared with OSC, liver metastases had a stronger impact on the prognosis of patients with OCCC. T3-stage, positive distant lymph nodes metastases, and lung metastases were risk factors for developing liver metastases. Chemotherapy was an independent prognostic factor for patient with advanced OCCC, but had no effect on CSS in patients with liver metastases (p = 0.0656), while surgery was significantly related with better CSS in these patients (p < 0.0001) (p = 0.0041). GPC3 expression was detected in all tissue sections, and GPC3 staining was predominantly found in the cytoplasm and membranes. CONCLUSION: Advanced OCCC and OCCC with liver metastases are two types of high-risk OCCC. The constructed nomogram exhibited a satisfactory survival prediction for patients with advanced OCCC. GPC3 immunohistochemistry is expected to accumulate preclinical evidence to support the inclusion of GPC3 in OCCC targeted therapy.
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Adenocarcinoma de Células Claras , Cistadenocarcinoma Seroso , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/metabolismo , Persona de Mediana Edad , Pronóstico , Anciano , Adenocarcinoma de Células Claras/patología , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/mortalidad , Programa de VERF , Adulto , Nomogramas , Factores de RiesgoRESUMEN
INTRODUCTION: Gastrointestinal symptoms as well as depression and anxiety can negatively affect the effectiveness of military training and combat in general. This cross-sectional study aimed to determine the prevalence of gastrointestinal symptoms in recruits and further validate their associations with depression and anxiety. METHODS: A self-report questionnaire was sent to the recruits in an army in April 2022, which primarily included the Symptom Rating Scale (GSRS) for the assessment of gastrointestinal symptoms, the Bristol Stool Scale (BSS) for stool consistency and shape, the Patient Health Questionnaire-9 (PHQ-9) for depression, and the 7-item Generalized Anxiety Disorder scale (GAD-7) for anxiety. Correlation of gastrointestinal symptoms with depression and anxiety was evaluated. RESULTS: Overall, 467 recruits were included. Their median age was 21.0 years old (range: 18.0-24.0), and 98.1% of them were male. The proportion of gastrointestinal symptoms, abnormal stools, depression, and anxiety was 69.2% (n = 323), 11.3% (n = 53), 17.6% (n = 82), and 12.2% (n = 57), respectively. The recruits with gastrointestinal symptoms evaluated by GSRS had significantly higher prevalence of depression (P < 0.001) and anxiety (P < 0.001) than those without. GSRS score positively correlated with PHQ-9 (rs = 0.440, P < 0.001) and GAD-7 score (rs = 0.386, P < 0.001). CONCLUSION: Gastrointestinal symptoms are very common in recruits, and positively correlate with depression and anxiety.
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Ansiedad , Depresión , Enfermedades Gastrointestinales , Humanos , Estudios Transversales , Masculino , Femenino , Adulto Joven , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/psicología , Adolescente , Depresión/epidemiología , Ansiedad/epidemiología , Prevalencia , Personal Militar/psicología , Personal Militar/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios , AutoinformeRESUMEN
Computer-assisted full facial imaging systems are currently among the most widely used skin analysis instruments in dermatology and medical cosmetology. These systems offer objective quantitative evaluation of facial skin conditions, and as they are non-invasive, play an important role in assessing dermatological conditions such as pigmentation, inflammation, vascular diseases, skin texture, the severity of ageing, and therapeutic follow-up. Although computer-assisted full facial imaging systems enable quantitative analysis in the scope of medical treatment and cosmetic evaluation, their results may considerably vary because of the influence of environmental and postural factors for improper operation. Furthermore, manual observation is sometimes necessary for experimental work for more accuracy, and familiarity with the imaging principles and application points is necessary to best apply this technique. This report aims to discuss and interpret these systems' imaging mechanisms and explore the primary issues with their application.
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BACKGROUND: Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. METHODS: 10 × Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. RESULTS: We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. CONCLUSION: Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.
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Células Madre Mesenquimatosas , Insuficiencia Ovárica Primaria , Humanos , Femenino , Animales , Ratones , Anciano , Insuficiencia Ovárica Primaria/terapia , Oocitos , Células Madre , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genéticaRESUMEN
The monitoring unit used in the nuclear magnetic resonance system, as an important unit of the system, faces a high thermal risk during its entire life cycle. This paper ensures the high efficiency and reliability of the thermal design of the product module from the two dimensions of structural design and device derating design. In order to reduce the risk of thermal design of electronic modules and comprehensively verify the effectiveness of thermal design of electronic modules, the design verification is carried out by combining simulation and experiment. In the simulation process, by establishing a thermal simulation model at the circuit board level, the crustal temperature of the core device is numerically calculated, and the index is compared with the thermal design index value and the test value, on the one hand, to verify the correctness of the simulation model. On the other hand, the validity of thermal design is verified. In the testing process, a thermal test platform for product modules is built, and the thermal characteristics test values of the core components of the module under extreme electrical conditions are obtained, and the corresponding conversion methods are used to predict the thermal performance and thermal design margin of the product at different altitudes. The results show that the electronic module can meet the thermal design requirements in terms of structural design and derating design of core components, and can ensure that the product module can work safely and reliably during the entire life cycle of the NMR system.
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Electrónica , Imagen por Resonancia Magnética , Reproducibilidad de los Resultados , Temperatura , Espectroscopía de Resonancia MagnéticaRESUMEN
BACKGROUND AND AIMS: Abdominal gunshot wounds (GSWs), a clinically devastating injury, can result in a variety of severe and lethal complications. Traditionally, exploratory laparotomy is the first-line approach for the management of abdominal GSWs, but it is associated with a considerable amount of unnecessary surgeries. At present, selective non-operative management (SNOM) of abdominal GSWs is becoming an effective and well-recognized approach, but it remains widely disputed since many surgeons are skeptical about the validity of SNOM in clinical practice. This meta-analysis aims to estimate the outcomes of SNOM and immediate laparotomy in patients with GSWs by collecting the currently available evidence. METHODS: The PubMed , EMBASE , and Cochrane Library databases were searched. A random-effects model was employed. A pooled proportion with 95% confidence intervals (CIs) was calculated. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. RESULTS: Overall, 53 studies involving 60 291 participants were included. The pooled proportions of SNOM and SNOM failure were 27.0% (95% CI=24.0-30.0%) and 10.0% (95% CI=7.0-13.0%), respectively. The pooled mortality after SNOM and SNOM failure were 0.0% (95% CI=0.0-1.0%) and 0.0% (95% CI=0.0-0.0%), respectively. The pooled proportions of immediate laparotomy and unnecessary immediate laparotomy were 73.0% (95% CI=70.0-76.0%) and 10.0% (95% CI=8.0-13.0%), respectively. The pooled mortality after immediate laparotomy and unnecessary immediate laparotomy was 10.0% (95% CI=8.0-13.0%) and 0.0% (95% CI=0.0-1.0%), respectively. Heterogeneity was statistically significant in nearly all meta-analyses. CONCLUSION: Immediate laparotomy is still the mainstay approach for the management of abdominal GSWs. Approximately one-third of patients with abdominal GSWs undergo SNOM. SNOM failure is not frequent, and its related mortality is also rare.
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Traumatismos Abdominales , Heridas por Arma de Fuego , Adulto , Humanos , Heridas por Arma de Fuego/cirugía , Traumatismos Abdominales/cirugía , Laparotomía , Bases de Datos FactualesRESUMEN
In this study, a surface-enhanced Raman spectroscopy (SERS) magnetic sensor is established based on SERS principle and magnetic separation technology, and a highly sensitive, simple and fast method for quantitative detection of neutralizing antibodies (nABs) and specific IgG of SARS-CoV-2 in plasma is established combined with immunoassay. Two kinds of Raman nanospheres (RNPs) with different characteristic Raman shifts are used as signal sources and coupled to ACE2 and anti-IgG (FC) antibodies respectively, and magnetic beads are coupled to RBD. The competitive relationship between ACE2 and nABs, the binding relationship between specific IgG and anti-IgG (FC) antibodies are determined. The results show that the concentrations of nABs and specific IgG in the range of 10-2000 ng ml-1are well correlated with SERS response intensity, and the recoveries are both between 90%-110%, with good precision. Bilirubin and common anticoagulants have no interference on the detection results. This method is accurate, reliable, sensitive and does not require complex pre-treatment, and is expected to be used for simultaneous detection of nABs and specific IgG in plasma of SARS-CoV-2. It has guiding significance for the development and evaluation of vaccines and the formulation of individualized vaccination schedule.
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COVID-19 , SARS-CoV-2 , Humanos , Enzima Convertidora de Angiotensina 2 , COVID-19/diagnóstico , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Espectrometría Raman , Fenómenos Magnéticos , Inmunoglobulina GRESUMEN
Background and Aim: Clinical manifestations of rosacea include transient or persistent facial erythema, telangiectasia, papules, and pustules. The existing assessment tools primarily evaluate the facial area to assess the severity of rosacea. However, in addition to the face, telangiectasia, erythema, and flushing can occur in the ear. Here, we investigated the correlation between the dermoscopic characteristics of capillaries in the earlobe and auricle and the types and severity of rosacea. Materials and Methods: Experienced dermatologists evaluated the clinical type, medical history, severity, and distribution pattern of facial erythema. The clinical severity of rosacea was assessed using the standard grading system (SGS), clinician's erythema assessment (CEA), and investigator's global assessment (IGA). Relationships of the clinical types and severity with the dermoscopic characteristics of capillaries in the earlobe and auricle were further analyzed. Results: In total, 145 patients with rosacea were enrolled in this study. We found that SGS, CEA, and IGA correlated well with the dermoscopic features of capillaries in the earlobe (R = 0.357, 0.357, and 0.314, respectively) (p < 0.001) and auricle (R = 0.423, 0.443, and 0.374, respectively) (p < 0.001). However, there was no significant correlation between the features and types of rosacea. Conclusion: The dermoscopic characteristics of capillaries in the earlobe and auricle can be used as indicators of the clinical severity of rosacea, regardless of the clinical subtype.
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Due to production and assembly errors of magnets resulting in reduced magnetic field homogeneity, passive shimming (PS) is necessary when Halbach magnets are used in high-resolution Benchtop Nuclear Magnetic Resonance (BNMR) spectrometer. The conventional PS technique, which places independent PS devices inside the magnet aperture, is no longer applicable to small-aperture compact high-field-strength Halbach magnet studies. In this paper, based on spherical harmonic function expansion, we improve the magnetic field homogeneity by optimizing the moving step of the magnet moving arrays composed of Halbach magnets to generate the corresponding harmonic terms to compensate for the magnetic field. With this approach, the homogeneity of a 1 T Halbach magnet was improved from the original 3913 ppm to 8 ppm in a L10 mm × R2.5 mm of 0.64% copper sulfate doped water sample. This work explores the PS mechanism based on the movement of magnetic blocks, which can be applied in BNMR and other compact high-field strength high-homogeneity Halbach magnets application circumstances.
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Globo-H (GH), a globo-series glycosphingolipid antigen that is synthesized by key enzymes ß1,3-galactosyltransferase V (ß3GalT5), fucosyltransferase (FUT) 1 and 2, is highly expressed on a variety of epithelial cancers rendering it a promising target for cancer immunotherapy. GH-targeting antibody-drug conjugate has been demonstrated an excellent tumor growth inhibition potency in animal models across multiple cancer types including Gastric cancer (GC). This study aims to further investigate the GH roles in GC. Significant correlations were observed between high mRNA expression of GH-synthetic key enzymes and worse overall survival (OS)/post-progression survival for GC patients based on the data from "Kaplan-Meier plotter" database (n=498). The level of GH expression was evaluated in clinical adenocarcinoma samples from 105 patients with GC by immunohistochemistry based on H-score. GH expression (H score ≥ 20; 33.3%) was significantly associated with a poor disease specific survival (DSS) and invasiveness in all samples with P=0.029 and P=0.013, respectively. In addition, it is also associated with shorter DSS and OS in poorly differentiated tumors with P=0.033 and P=0.045, respectively. Particularly, with patients ≥ 65 years of age, GH expression is also significantly associated with the stages (P=0.023), differentiation grade (P=0.038), and invasiveness (P=0.026) of the cancer. Sorted GC NCI-N87 cells with high level of endogenous GH showed higher proliferative activity compared with low-GH-expressing cells based on PCNA expression. Micro-western array analysis on high-GH-expressing GC cells indicated an upregulation in HER2-related signaling proteins including phospho-AKT/P38/JNK and Cyclin D1/Cyclin E1 proteins. Moreover, GH level was shown to be correlated with expression of total HER2 and caveolin-1 in GC cells. Immunoprecipitation study suggested that there are potential interactions among GH, caveolin-1, and HER2. In conclusions, GH level was significantly associated with the worse survival and disease progression in GC patients, especially in older patients. Enhanced cell proliferation activity through interactions among GH, HER2, and caveolin-1 interactions may contribute to GH induced tumor promotion signaling in GC. GH-targeting therapy may be a viable option for the treatment of GC patients.
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BACKGROUND: Gastrointestinal symptoms and psychological problems are common in youths, which can negatively affect their lives on physical, mental, and social levels. This cross-sectional study aimed to determine the prevalence of gastrointestinal symptoms in youths and further explore their association with psychological problems. METHODS: Self-reported data on gastrointestinal symptoms and psychological problems in 692 sophomores who majored in education in a high vocational school and 310 recruits who were undergoing basic training in an army in China were retrospectively collected. The self-reported data included demographics, gastrointestinal symptoms, and Symptom Checklist 90 (SCL-90) used for the assessment of psychological problems. Gastrointestinal symptoms surveyed included nausea, emesis, abdominal pain, acid regurgitation, eructation, heartburn, anorexia, abdominal bloating, diarrhea, constipation, hematemesis, and hematochezia. Logistic regression analysis was performed to identify the independent risk factors associated with gastrointestinal symptoms. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. RESULTS: The prevalence of gastrointestinal symptoms was 36.7% (n=254) and 15.5% (n=48) in the sophomores and recruits, respectively. Participants with gastrointestinal symptoms had a significantly higher prevalence of total SCL-90 score beyond 160 than those without gastrointestinal symptoms in both sophomores (19.7% vs. 3.2%, P<0.001) and recruits (10.4% vs. 1.1%, P<0.001). Total SCL-90 score beyond 160 was independently associated with gastrointestinal symptoms in both sophomores (OR =5.467; 95% CI: 2.855-10.470; P<0.001) and recruits (OR =6.734; 95% CI: 1.226-36.999; P=0.028). CONCLUSIONS: Gastrointestinal symptoms may be common and strongly associated with psychological problems in youths. Prospective studies should be required to explore the impact of the correction of psychological problems on the improvement of gastrointestinal symptoms.
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Dolor Abdominal , Humanos , Adolescente , Estudios Retrospectivos , Prevalencia , Estudios Transversales , Estudios Prospectivos , Dolor Abdominal/diagnóstico , Dolor Abdominal/epidemiologíaRESUMEN
In engineering acoustics, the propagation of elastic flexural waves in plate and shell structures is a common transmission path of vibrations and structure-borne noises. Phononic metamaterials with a frequency band gap can effectively block elastic waves in certain frequency ranges, but often require a tedious trial-and-error design process. In recent years, deep neural networks (DNNs) have shown competence in solving various inverse problems. This study proposes a deep-learning-based workflow for phononic plate metamaterial design. The Mindlin plate formulation was used to expedite the forward calculations, and the neural network was trained for inverse design. We showed that, with only 360 sets of data for training and testing, the neural network attained a 2% error in achieving the target band gap, by optimizing five design parameters. The designed metamaterial plate showed a -1 dB/mm omnidirectional attenuation for flexural waves around 3 kHz.
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In this study, by comparing the UV-vis spectral characteristics of colloidal gold and colloidal gold enhancer, and their differences as immunochromatographic tracers in the qualitative detection of PCT, IL-6, Hp and quantitative determination of PCT performance, the factors that may affect the sensitivity were discussed. The results show that the absorbance at 520 nm of CGE diluted 20-fold and colloidal gold diluted 2-fold were comparable, and the sensitivity of CGE immunoprobe for qualitative detection of PCT, IL-6 and Hp was higher than that of colloidal gold immunoprobe, and the reproducibility and accuracy of both immunoprobes for quantitative detection of PCT were good. Indicating that the high sensitivity of CGE immunoprobe detection is mainly due to the absorption coefficient of CGE at 520 nm is about 10 times that of colloidal gold immunoprobe, CGE has stronger light absorption capacity and stronger quenching effect on rhodamine 6 G on the nitrocellulose membrane surface of the test strip.
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Oro Coloide , Interleucina-6 , Biomarcadores , Cromatografía de Afinidad/métodos , Oro Coloide/química , Reproducibilidad de los Resultados , NanoestructurasRESUMEN
No previous research has examined cognitive-motor interference (CMI) repeatedly in patients with subacute stroke. This pilot study aimed to report on the changes over time in CMI in patients with stroke who have recently learned to walk with a cane. The assessment started as soon as the participants could walk independently with a quad cane, and was repeated up to six sessions as long as the cane was still used. The dual-tasking paradigm required participants to walk and perform continuous subtractions by 3s. Data were analyzed for 9 participants 33-127 days post-stroke. All 9 participants showed CMI in walking velocity at baseline and 8 of these showed improvement over time (Z = -2.547; p = 0.011). The improvement in CMI was associated with baseline dual-tasking performance (ρ = 0.600; p = 0.044), motor control ability (ρ = -0.695; p = 0.019), walking velocity (ρ = -0.767; p = 0.008), and functional mobility (ρ = 0.817; p = 0.004). All participants showed decrements in both tasks (mutual interference) at baseline, 1 evolved to decrements in walking velocity (cognitive-related motor interference), and 3 finally evolved to decrements in cognitive performance but increments in walking velocity (motor-priority tradeoff). In conclusion, during rehabilitation with cane walking in patients with subacute stroke, the dual-tasking paradigm revealed CMI and its improvements in the majority of participants. Greater improvement in CMI was moderately to strongly associated with worse baseline performance of many variables. The evolution of the CMI pattern over time provides novel information relevant to neurological recovery.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Bastones , Cognición , Marcha , Humanos , Proyectos Piloto , Desempeño Psicomotor , CaminataRESUMEN
Cervical cancer (CC) is a malignancy that tends to have a poor prognosis when detected at an advanced stage; however, there are few studies on the early detection of CC at the genetic level. The tumor microenvironment (TME) and genomic instability (GI) greatly affect the survival of tumor patients via effects on carcinogenesis, tumor growth, and resistance. It is necessary to identify biomarkers simultaneously correlated with components of the TME and with GI, as these could predict the survival of patients and the efficacy of immunotherapy. In this study, we extracted somatic mutational data and transcriptome information of CC cases from The Cancer Genome Atlas, and the GSE44001 dataset from the Gene Expression Omnibus database was downloaded for external verification. Stromal components differed most between genomic unstable and genomic stable groups. Differentially expressed genes were screened out on the basis of GI and StromalScore, using somatic mutation information and ESTIMATE methods. We obtained the intersection of GI- and StromalScore-related genes and used them to establish a four-gene signature comprising RIPOR2, CCL22, PAMR1, and FBN1 for prognostic prediction. We described immunogenomic characteristics using this risk model, with methods including CIBERSORT, gene set enrichment analysis (GSEA), and single-sample GSEA. We further explored the protective factor RIPOR2, which has a close relationship with ImmuneScore. A series of in vitro experiments, including immunohistochemistry, immunofluorescence, quantitative reverse transcription PCR, transwell assay, CCK8 assay, EdU assay, cell cycle detection, colony formation assay, and Western blotting were performed to validate RIPOR2 as an anti-tumor signature. Combined with integrative bioinformatic analyses, these experiments showed a strong relationship between RIPOR2 with tumor mutation burden, expression of genes related to DNA damage response (especially PARP1), TME-related scores, activation of immune checkpoint activation, and efficacy of immunotherapy. To summarize, RIPOR2 was successfully identified through comprehensive analyses of the TME and GI as a potential biomarker for forecasting the prognosis and immunotherapy response, which could guide clinical strategies for the treatment of CC patients.
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Neoplasias del Cuello Uterino , Biomarcadores de Tumor/genética , Femenino , Inestabilidad Genómica , Humanos , Pronóstico , Microambiente Tumoral/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
Acute pulmonary embolism (APE) is a debilitating condition with high incidence and mortality rates. APE is widely treated with the serine protease urokinase or urokinase-type plasminogen activator (uPA) that functions by resolving blood clots via catalyzing the conversion of plasminogen to plasmin. Treatment with recombinant uPA has been shown to increase endogenous expression of uPA and its cognate receptor, uPAR; however, the mechanisms for this induction are not known. Using an in vitro hypoxia/reoxygenation model in bronchial epithelial BEAS-2B cells, we show that induction of hypoxia/reoxygenation induces apoptosis and increases secretion of tumor necrosis factor-alpha, brain natriuretic peptide, and fractalkine, which are attenuated when treated with exogenous uPA. Induction of hypoxia/reoxygenation resulted in decreased expression of uPAR on cell surface without any significant changes in its messenger RNA expression, highlighting post-transcriptional regulatory mechanisms. Determination of uPAR protein half-life using cycloheximide showed treatment with uPA significantly increased its half-life (209.6 ± 0.2 min from 48.2 ± 2.3 min). Hypoxia/reoxygenation promoted the degradation of uPAR. Inhibition of proteasome-mediated degradation using MG-132 and lactacystin revealed that uPAR was actively degraded when hypoxia/reoxygenation was induced and that it was reversed when treated with exogenous uPA. Determination of the proteolytic activity of 20S proteasome showed a global increase in ubiquitin-proteasome activation without an increase in proteasome content in cells subjected to hypoxia/reoxygenation. Our results cumulatively reveal that uPAR is actively degraded following hypoxia/reoxygenation, and the degradation was significantly weakened by exogenous uPA treatment. Given the importance of the uPA/uPAR axis in a multitude of pathophysiological contexts, these findings provide important yet undefined mechanistic insights.
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BACKGROUND AND AIMS: The doses of medications may influence the success of Helicobacter pylori (H. pylori) eradication. This real-world observational study aimed to explore the impact of insufficient doses of medications prescribed for the bismuth-containing quadruple therapy (BQT) regimen on successful H. pylori eradication. METHODS: We retrospectively screened the patients who were diagnosed with H. pylori infection and received BQT regimens for H. pylori eradication at our department between January 2017 and July 2020. The rate of successful H. pylori eradication was compared according to the doses of medications prescribed. Standard doses were defined according to the clinical guidelines. RESULTS: Overall, 1054 patients were included. The rate of successful H. pylori eradication was 78.2% (824/1054). Among them, proton pump inhibitors (PPIs) and antibiotics were prescribed at insufficient doses in 37.0% (390/1054) and 6.7% (71/1054) of patients, respectively. Furthermore, pantoprazole (98.7% [385/390]) was the most common type of PPIs prescribed at insufficient doses, and nitroimidazoles (85.9% [61/71]) were the most common type of antibiotics prescribed at insufficient doses. Among the patients receiving colloidal bismuth pectin (CBP) (200 mg tid) and standard-dose antibiotics, the rate of successful H. pylori eradication was lower in insufficient-dose PPIs group than standard-dose PPIs group (78.1% [271/347] versus 82.6% [438/530], P = 0.095). Among the patients receiving CBP (200 mg tid) and standard-dose PPIs, the rate of successful H. pylori eradication was significantly lower in insufficient-dose antibiotics group than standard-dose antibiotics group (37.8% [14/37] versus 82.6% [438/530], P < 0.0001). Among the patients receiving CBP 200 mg tid, the rate of successful H. pylori eradication was significantly lower in patients receiving both PPIs and antibiotics at insufficient doses than those at standard doses (46.4% [13/28] versus 82.6% [438/530], P < 0.0001). CONCLUSION: Among the BQT regimens, PPIs and/or antibiotics, especially pantoprazole and metronidazole, are often prescribed at insufficient doses, compromising the success of H. pylori eradication. ABBREVIATIONS: H. pylori, Helicobacter pylori; UBT, urea breath test; DPM, disintegrations per minute; BQT, bismuth-containing quadruple therapy; PPI, proton pump inhibitor; CBP, colloidal bismuth pectin; qd, once daily; bid, twice daily; tid, three times daily; qid, four times daily.
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Infecciones por Helicobacter , Helicobacter pylori , Nitroimidazoles , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Bismuto/uso terapéutico , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Metronidazol/uso terapéutico , Nitroimidazoles/uso terapéutico , Pantoprazol/uso terapéutico , Pectinas/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Estudios Retrospectivos , Urea/uso terapéuticoRESUMEN
The incidence and mortality of colorectal cancer (CRC) are ranked in the top three worldwide in 2020. Abundant studies have reported that circular RNAs (circRNAs) act critical roles in the genesis and development of tumors, including CRC. Nevertheless, the roles and detailed regulation mechanisms of circRNAs that are related to the initiation and development of CRC have not been fully found and clarified. This research primarily revealed that circTMEM59 was greatly downregulated in CRC tissues and cell lines via qRT-PCR. In addition, the decreased expression of circTMEM59 was closely related to adverse clinicopathological characteristics and the shorter survival time of CRC patients. Then, a further study found that the overexpression of circTMEM59 suppressed cell growth and accelerated the cell death of CRC via a series of experiments in vitro and in vivo. Furthermore, circTMEM59 also repressed the metastatic behaviors of CRC cells. Further study revealed that circTMEM59 played the role of competing endogenous RNAs (ceRNAs) by binding to miR-668-3p to increase the expression of inhibitor of DNA binding 4 (ID4) in CRC. In summary, the results of this study clarified the antitumor effects of circTMEM59/miR-668-3p/ID4 axis in CRC progression and provided potential therapeutic targets and clinical prognostic markers for CRC.
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Neoplasias Colorrectales , Proteínas Inhibidoras de la Diferenciación , MicroARNs , ARN Circular , Movimiento Celular , Proliferación Celular/fisiología , Neoplasias Colorrectales/patología , Humanos , Proteínas Inhibidoras de la Diferenciación/genética , Proteínas de la Membrana , MicroARNs/genética , Proteínas del Tejido Nervioso , ARN Circular/genéticaRESUMEN
Acute pulmonary embolism (APE) is a disabling diseases with high incidence rate and mortality rate. Although with high specificity, D-Dimer lacks specificity to assess APE, hence additional diagnostic and prognostic biomarkers are necessary. APE is widely treated with serine protease urokinase or urokinase-type plasminogen activator (uPA), which act as a catalyst for conversion of plasminogen to plasmin to resolve blood clots. However, it is unknown the role of differential expression of microRNAs (miRNAs) in protective effect of uPA against APE. Hence, we performed miRNA profiling in a hypoxia/reoxygenation (H/R) model of bronchial epithelial BEAS-2B cells in vitro and a APE mice model in vivo. Our analysis revealed that miR-34a-5p, miR-324-5p, miR-331-3p are upregulated with H/R or APE induction, whereas miR-429, miR-491-5p, and miR-449a are downregulated. The differential expression of the miRNAs was attenuated to levels comparable to control by treatment with uPA both in vitro and in vivo. In situ target prediction and analysis of potential functions of the target genes showed that the enrichment of biological processes and pathways were related to cell growth, proliferation, and inflammation. Ectopic overexpression of miR-449a using a mimic completely attenuated the protective effect of uPA in the H/R model in vitro. These results provide a group of miRNAs that could be used as markers, and the modulation of these miRNAs might have potential therapeutic benefits in patients with APE, which need to be validated in additional studies in humans.