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Pancreatic cancer is a globally recognized highly aggressive malignancy, posing a significant threat to human health and characterized by pronounced heterogeneity. In recent years, researchers have uncovered that the development and progression of cancer are often attributed to the accumulation of somatic mutations within cells. However, cancer somatic mutation data exhibit characteristics such as high dimensionality and sparsity, which pose new challenges in utilizing these data effectively. In this study, we propagated the discrete somatic mutation data of pancreatic cancer through a network propagation model based on protein-protein interaction networks. This resulted in smoothed somatic mutation profile data that incorporate protein network information. Based on this smoothed mutation profile data, we obtained the activity levels of different metabolic pathways in pancreatic cancer patients. Subsequently, using the activity levels of various metabolic pathways in cancer patients, we employed a deep clustering algorithm to establish biologically and clinically relevant metabolic subtypes of pancreatic cancer. Our study holds scientific significance in classifying pancreatic cancer based on somatic mutation data and may provide a crucial theoretical basis for the diagnosis and immunotherapy of pancreatic cancer patients.
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Genómica , Neoplasias Pancreáticas , Humanos , Pronóstico , Genómica/métodos , Neoplasias Pancreáticas/genética , Mutación , Análisis por ConglomeradosRESUMEN
Diabetes stands as one of the most prevalent chronic diseases globally. The conventional methods for diagnosing diabetes are frequently overlooked until individuals manifest noticeable symptoms of the condition. This study aimed to address this gap by collecting comprehensive datasets, including 1000 instances of blood routine data from diabetes patients and an equivalent dataset from healthy individuals. To differentiate diabetes patients from their healthy counterparts, a computational framework was established, encompassing eXtreme Gradient Boosting (XGBoost), random forest, support vector machine, and elastic net algorithms. Notably, the XGBoost model emerged as the most effective, exhibiting superior predictive results with an area under the receiver operating characteristic curve (AUC) of 99.90% in the training set and 98.51% in the testing set. Moreover, the model showcased commendable performance during external validation, achieving an overall accuracy of 81.54%. The probability generated by the model serves as a risk score for diabetes susceptibility. Further interpretability was achieved through the utilization of the Shapley additive explanations (SHAP) algorithm, identifying pivotal indicators such as mean corpuscular hemoglobin concentration (MCHC), lymphocyte ratio (LY%), standard deviation of red blood cell distribution width (RDW-SD), and mean corpuscular hemoglobin (MCH). This enhances our understanding of the predictive mechanisms underlying diabetes. To facilitate the application in clinical and real-life settings, a nomogram was created based on the logistic regression algorithm, which can provide a preliminary assessment of the likelihood of an individual having diabetes. Overall, this research contributes valuable insights into the predictive modeling of diabetes, offering potential applications in clinical practice for more effective and timely diagnoses.
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Diabetes Mellitus , Aprendizaje Automático , Humanos , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Femenino , Masculino , Máquina de Vectores de Soporte , Algoritmos , Curva ROC , Persona de Mediana Edad , Índices de Eritrocitos , AdultoRESUMEN
Antibodies specifically bind to antigens and are an essential part of the immune system. Hence, antibodies are powerful tools in research and diagnostics. High-throughput sequencing technologies have promoted comprehensive profiling of the immune repertoire, which has resulted in large amounts of antibody sequences that remain to be further analyzed. In this study, antibodies were downloaded from IMGT/LIGM-DB and Sequence Read Archive databases. Contributing features from antibody heavy chains were formulated as numerical inputs and fed into an ensemble machine learning classifier to classify the antigen specificity of six classes of antibodies, namely anti-HIV-1, anti-influenza virus, anti-pneumococcal polysaccharide, anti-citrullinated protein, anti-tetanus toxoid and anti-hepatitis B virus. The classifier was validated using cross-validation and a testing dataset. The ensemble classifier achieved a macro-average area under the receiver operating characteristic curve (AUC) of 0.9246 from the 10-fold cross-validation, and 0.9264 for the testing dataset. Among the contributing features, the contribution of the complementarity-determining regions was 53.1% and that of framework regions was 46.9%, and the amino acid mutation rates occupied the first and second ranks among the top five contributing features. The classifier and insights provided in this study could promote the mechanistic study, isolation and utilization of potential therapeutic antibodies.
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Secuencia de Aminoácidos , Anticuerpos/química , Aprendizaje Automático , Especificidad de Anticuerpos , Regiones Determinantes de Complementariedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Curva ROCRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). METHODS: We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center's cohort. RESULTS: We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. CONCLUSIONS: Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD.
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Biomarcadores , Trastorno Depresivo Mayor , Inflamación , Enfermedades Inflamatorias del Intestino , Mapas de Interacción de Proteínas , Humanos , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/genética , Biomarcadores/sangre , Biomarcadores/metabolismo , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/genética , Inflamación/sangre , Mapas de Interacción de Proteínas/genética , Curva ROC , Femenino , Masculino , Perfilación de la Expresión Génica , AdultoRESUMEN
OBJECTIVES: To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. RESULTS: After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). CONCLUSIONS: HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.
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Adenomiosis , Ultrasonido Enfocado de Alta Intensidad de Ablación , Resultado del Embarazo , Humanos , Femenino , Adenomiosis/cirugía , Adenomiosis/terapia , Embarazo , Adulto , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Estudios Retrospectivos , Infertilidad Femenina/terapiaRESUMEN
Managing pediatric Crohn's disease (PCD) presents challenges due to severe complications and higher biologic therapy needs. Transitioning from anti-tumor necrosis factor agents to off-label therapies adds complexity. Although upadacitinib has demonstrated efficacy and tolerability in adult inflammatory bowel disease and pediatric atopic dermatitis, there are limited data for its application in PCD. This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.
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BACKGROUND: Fruit flesh colour is not only an important commodity attribute of eggplant but is also closely related to maturity. However, very little is known about its formation mechanism in eggplant. RESULTS: Two inbred lines of eggplant, green 'NC7' and white 'BL', were used in this study to explain the differences in flesh colour. Transcriptome sequencing results revealed a total of 3304 differentially expressed genes (DEGs) in NC7 vs. BL. Of the DEGs obtained, 2050 were higher and 1254 were lower in BL. These DEGs were annotated to 126 pathways, where porphyrin and chlorophyll metabolism, flavonoid biosynthesis, and photosynthesis-antenna proteins play vital roles in the colour formation of eggplant flesh. At the same time, Gene Ontology (GO) enrichment significance analysis showed that a large number of unigenes involved in the formation of chloroplast structure were lower in BL, which indicated that the formation of chloroplasts in white-fleshed eggplant was blocked. This was confirmed by transmission electron microscopy (TEM), which found only leucoplasts but no chloroplasts in the flesh cells of white-fleshed eggplant. Several genes encoding ERF and bHLH transcription factors were predicted to participate in the regulation of chlorophyll biosynthetic genes. CONCLUSIONS: The results of this study indicated that differences in the gene expression of the chlorophyll metabolic pathway were the main cause of the different flesh colour formations. These findings will increase our understanding of the genetic basis in eggplant flesh colors formation mechanism.
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Solanum melongena , Solanum melongena/genética , Solanum melongena/metabolismo , Transcriptoma , Color , Perfilación de la Expresión Génica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
OBJECTIVES: To evaluate the timing and safety of hysteroscopic myomectomy for large submucosal fibroids pretreated with high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: From June 2011 to December 2020, 74 patients with solitary submucousal fibroid with size larger than 4 cm who received HIFU treatment followed by hysteroscopic myomectomy were enrolled. RESULTS: The average age of patients was 40.2 ± 6.7 years. Among them, 1 had type 0, 18 had type I and 55 patients had type II submucosal fibroids. The mean diameter of fibroids was 5.7 ± 1.2 cm. All patients completed HIFU in one session, and the median non-perfused volume (NPV) ratio achieved in fibroids was 90.5%. Hysteroscopic myomectomy was performed in 0-1, 1-3, 3-6, and 6-12 months after HIFU. The mean shrinkage rate of fibroids post-HIFU was 68.19 ± 19.86%, 61.10 ± 16.89%, and 63.76 ± 26.68% in 1-3 months, 3-6 months and 6-12 months, respectively. All patients completed hysteroscopic myomectomy successfully, and no intrauterine adhesion after HIFU was observed. The complete resection of fibroids achieved in 69 patients in one session of the procedure. The mean operation time was 66.66 ± 31.61 min, the median blood loss was 20 ml, and the median distention medium deficit was 275 ml. No significant difference was observed in the operation time, blood loss and distention medium deficit among patients who received hysteroscopic myomectomy at different time points (p > 0.05). CONCLUSIONS: HIFU can be used as a pretreatment for large submucosal fibroids before hysteroscopic myomectomy. Based on our results, hysteroscopic myomectomy could be performed at any time point, even within 1 month after HIFU.
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Leiomioma , Miomectomía Uterina , Humanos , Femenino , Adulto , Persona de Mediana Edad , Leiomioma/diagnóstico por imagen , Leiomioma/cirugíaRESUMEN
Epinodosin has shown antibacterial and antitumor biological characteristics in the documents. We found that Epinodosin has an effective inhibitory effect on esophageal squamous cell carcinoma (ESCC). However, the potential roles and mechanisms of Epinodosin in ESCC remain unclear. We performed many experiments to clarify the effect and mechanism of Epinodosin on ESCC. In this study, cell viability, invasion, migration, and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,-diphenytetrazoliumromide (MTT), Transwell, and flow cytometry. The differentially expressed miRNAs were screened through RNA transcriptome sequencing. The expression levels of miRNA-143-3p and some proteins were measured by real-time polymerase chain reaction (PCR) and Western blot. The anticancer effects of Epinodosin in vivo were determined by a nude mouse model. Epinodosin suppressed cell proliferation/invasion/migration and induced ESCC cell apoptosis. Epinodosin remarkably affected the protein expression of mitogen-activated protein kinase (MAPK) signaling pathway. The animal experiments demonstrated that Epinodosin could attenuate the growth of ESCC tumors in nude mice. The expression of p53, Bim, and Bax was upregulated, while that of Bcl-2 was downregulated in tumor tissues. In conclusion, Epinodosin suppresses cell viability/invasion/migration, while induces ESCC cell apoptosis by mediating miRNA-143-3p and Bcl-2, and can markedly attenuate the growth of ESCC tumors in nude mice.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Animales , Ratones , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Ratones Desnudos , Neoplasias Esofágicas/tratamiento farmacológico , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Polar topologies have received extensive attention due to their exotic configurations and functionalities. Understanding their responsive behaviors to external stimuli, especially thermal excitation, is highly desirable to extend their applications to high temperature, which is still unclear. Here, combining in situ transmission electron microscopy and phase-field simulations, the thermal dynamics of the flux-closure domains were illuminated in PbTiO3/SrTiO3 multilayers. In-depth analyses suggested that the topological transition processes from a/c domains to flux-closure quadrants were influenced by the boundary conditions of PbTiO3 layers. The symmetrical boundary condition stabilized the flux-closure domains at higher temperature than in the asymmetrical case. Furthermore, the reversible thermal responsive behaviors of the flux-closure domains displayed superior thermal stability, which maintained robust up to 450 °C (near the Curie temperature). This work provides new insights into the dynamics of polar topologies under thermal excitation and facilitates their applications as nanoelectronics under extreme conditions.
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This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.
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Neoplasias del Colon , Microambiente Tumoral , Ratones , Animales , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Fluorouracilo/farmacología , Polisacáridos/farmacología , Linfocitos T CD8-positivos/metabolismo , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging. METHODS: In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets. RESULTS: Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected. Systematically network analysis presented CRs genetic interactions have biological function relationship. Furthermore, we validated CRs genetic interactions induce multiple omics deregulation in The Cancer Genome Atlas. We revealed the colon adenocarcinoma patients (COAD) with mutations of a CRs set (EP300, MSH6, NSD2 and TRRAP) mediate a better survival with low expression of MAP2 and could benefit from taxnes. While the COAD patients carrying at least one of the CSV interactions in Vorinostat CSV module confer a poor prognosis and may be resistant to Vorinostat treatment. CONCLUSIONS: The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy.
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Adenocarcinoma , Neoplasias del Colon , Biomarcadores , Cromatina , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Proteínas de Unión al ADN , Humanos , VorinostatRESUMEN
BACKGROUND: Ursolic acid (UA) is a pentacyclic triterpenoid compound with a wide range of anti-tumor, anti-inflammatory, hypotensive and other pharmacological effects. Here, the biological roles and regulatory mechanisms of UA in influenza A virus (IAV)-treated A549 cells were investigated. METHOD: The cytotoxic impacts of UA on A549 cells with or without IAV treatment were determined using MTT and LDH assays. The inflammatory responses and oxidative stress of IAV-treated A549 cells were measured by RT-qPCR, ELISA, DCFH-DA probe, and colorimetric assays. A dual luciferase assay was carried out to validate the molecular interaction between miR-34c-5p and TLR5. Promoter methylation was detected by MSP experiment. Methylation-related proteins were quantified by western blot. Virus replication was assessed by TCID50 and western blot assays. RESULTS: UA significantly ameliorated IAV-triggered cell injury and inflammatory response, virus replication and oxidative stress by elevating cell viability, ROS level and the activities of SOD and GSH-Px but reducing the LDH, MDA, and TCID50 values and the expression of virus-related proteins (NP) and cytokines (TNF-α, IL-1ß, IL-6, and IL-18). Moreover, UA promoted miR-34c-5p expression by repressing DNMTs-mediated methylation. TLR5 was verified to be a direct target of miR-34c-5p and could be downregulated by UA. Rescue experiments revealed that silencing miR-34c-5p diminished the regulatory roles of UA in IAV-treated A549 cells. CONCLUSION: Our data elucidated that UA attenuated IAV-triggered inflammatory responses and oxidative stress in A549 cells by regulating the miR-34c-5p/TLR5 axis, suggesting that UA plays a protective role in IAV-induced pneumonia.
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Antineoplásicos , Virus de la Influenza A , MicroARNs , Triterpenos , Células A549 , Antineoplásicos/uso terapéutico , Apoptosis , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Estrés Oxidativo , Receptor Toll-Like 5/metabolismo , Triterpenos/farmacología , Triterpenos/uso terapéutico , Ácido UrsólicoRESUMEN
BACKGROUND: MicroRNAs (miRNAs) are considered potential biomarkers for various diseases. This study investigated whether hsa-miR-320a-3p and hsa-miR-483-5p levels in human ovarian granulosa cells derived from follicular fluids are associated with embryo developmental competence. METHODS: We collected 195 granulosa cells samples and analyzed the treatment outcomes in patients undergoing in vitro fertilization (n = 147) or intracytoplasmic sperm injection (n = 48) cycles. The hsa-miR-320a-3p and hsa-miR-483-5p levels in granulosa cells were measured using quantitative reverse transcription-polymerase chain reaction. RESULTS: Patients were subdivided into four groups according to the granulosa cells hsa-miR-320a-3p and hsa-miR-483-5p levels quartiles (Q1-Q4). Embryo developmental competence was compared using the chi-square test. Patients in Q3 were less likely to achieve a normal fertilization rate for in vitro fertilization and blastocyst formation than those in Q1 as they expressed high levels of hsa-miR-320a-3p and hsa-miR-483-5p (P < 0.05). Patients in Q3 and Q4 were less likely to achieve a good-quality embryo as they expressed high levels of hsa-miR-483-5p and hsa-miR-320a-3p (P < 0.05). The hsa-miR-320a-3p and hsa-miR-483-5p levels were not associated with clinical pregnancy. However, multiple regression analysis indicated that in Q3 and Q4 intervals had experienced a decreased chance of live birth due to high expression levels of hsa-miR-320a-3p and hsa-miR-483-5p levels. The relative hsa-miR-320a-3p expression levels in granulosa cells were weakly and positively correlated with the patient age (P = 0.0033). Moreover, both the basal follicle stimulating hormone (P = 0.0003) and ovarian stimulation protocols (P = 0.006 and P = 0.004) significantly and positively affected hsa-miR-320a-3p levels. The days of stimulation was negatively correlated with the relative hsa-miR-320a-3p expression level (P = 0.047). CONCLUSIONS: The hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells negatively correlated with the good-quality embryo rate and live birth, indicating that hsa-miR-320a-3p and hsa-miR-483-5p can be used as potential negative indicators to predict good-quality embryos and live births.
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Nacimiento Vivo , MicroARNs , Femenino , Embarazo , Humanos , Masculino , Nacimiento Vivo/genética , Inyecciones de Esperma Intracitoplasmáticas , Semen/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células de la Granulosa/metabolismo , BiomarcadoresRESUMEN
GOALS: To evaluate the outcomes of endoscopic submucosal dissection (ESD) for rectal tumors extending to the dentate line (RTDLs) compared with rectal tumors not extending to the dentate line (non-RTDLs). BACKGROUND: There is limited composite data on the outcomes of ESD for RTDLs versus non-RTDLs. STUDY: We performed a systematic review and meta-analysis of studies that reported the clinical outcomes of ESD for RTDLs and non-RTDLs. Main outcomes were pooled estimated rates of en bloc/complete/curative resection, local recurrence, and incidence of bleeding, perforation, stricture, anal pain, and fever. RESULTS: Six studies were enrolled, including 265 cases of RTDLs and 788 cases of non-RTDLs. The en bloc resection rate was comparable for RTDLs and non-RTDLs [odds ratio (OR), 1.04; 95% confidence interval (CI), 0.55-1.95; P=0.90]. The complete resection rate was significantly lower for RTDLs (OR, 0.59; 95% CI, 0.41-0.83; P=0.003), as well as the curative resection rate (OR, 0.57; 95% CI, 0.38-0.87; P=0.010). The rates of stricture, postoperative anal pain and local recurrence were significantly higher for RTDLs than non-RTDLs (OR, 3.07; 95% CI, 1.01-9.31; P=0.05) (OR, 42.10; 95% CI, 4.73-374.97; P=0.0008) (OR, 3.00; 95% CI, 1.13-7.96; P=0.03), but the higher rates of postoperative bleeding and fever for RTDLs were not significantly (OR, 1.33; 95% CI, 0.53-3.30; P=0.54) (OR, 2.23; 95% CI, 0.55-9.07; P=0.26), as well as its lower perforation rate (OR, 0.85; 95% CI, 0.27-2.63; P=0.78). CONCLUSIONS: Despite its inferior outcomes than non-RTDLs, ESD is still a feasible and safe treatment for RTDLs if appropriate lesions are treated by experienced operators.
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Resección Endoscópica de la Mucosa , Neoplasias del Recto , Constricción Patológica , Resección Endoscópica de la Mucosa/efectos adversos , Humanos , Recurrencia Local de Neoplasia/epidemiología , Dolor , Hemorragia Posoperatoria , Neoplasias del Recto/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: A range of strict nonpharmaceutical interventions (NPIs) were implemented in many countries to combat the coronavirus 2019 (COVID-19) pandemic. These NPIs may also be effective at controlling seasonal influenza virus infections, as influenza viruses have the same transmission path as severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate the effects of different NPIs on the control of seasonal influenza. METHODS: Data for 14 NPIs implemented in 33 countries and the corresponding influenza virological surveillance data were collected. The influenza suppression index was calculated as the difference between the influenza positivity rate during its period of decline from 2019 to 2020 and during the influenza epidemic seasons in the previous 9 years. A machine learning model was developed using an extreme gradient boosting tree regressor to fit the NPI and influenza suppression index data. The SHapley Additive exPlanations tool was used to characterize the NPIs that suppressed the transmission of influenza. RESULTS: Of all NPIs tested, gathering limitations had the greatest contribution (37.60%) to suppressing influenza transmission during the 2019-2020 influenza season. The three most effective NPIs were gathering limitations, international travel restrictions, and school closures. For these three NPIs, their intensity threshold required to generate an effect were restrictions on the size of gatherings less than 1000 people, ban of travel to all regions or total border closures, and closing only some categories of schools, respectively. There was a strong positive interaction effect between mask-wearing requirements and gathering limitations, whereas merely implementing a mask-wearing requirement, and not other NPIs, diluted the effectiveness of mask-wearing requirements at suppressing influenza transmission. CONCLUSIONS: Gathering limitations, ban of travel to all regions or total border closures, and closing some levels of schools were found to be the most effective NPIs at suppressing influenza transmission. It is recommended that the mask-wearing requirement be combined with gathering limitations and other NPIs. Our findings could facilitate the precise control of future influenza epidemics and other potential pandemics.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias/prevención & control , Estaciones del AñoRESUMEN
AIM: To investigate the long non-coding RNA DLG1 Antisense RNA 1 (lncRNA DLG1-AS1) mechanism in cervical cancer cells with gemcitabine (GEM) resistance. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect DLG1-AS1, miR-16-5p, and hepatoma-derived growth factor (HDGF) expression in cervical cancer cells. The effects of DLG1-AS1 knockdown on cell viability, proliferation, and apoptosis were investigated in GEM-resistant cervical cancer cells. The binding of DLG1-AS1 with miR-16-5p and of miR-16-5p with HDGF was confirmed through dual-luciferase reporter assays. HDGF expression was detected through Western blotting. A xenograft model was established using stably transfected GEM-resistant cervical cancer cells to detect the role of DLG1-AS1 in tumorigenesis in vivo. RESULTS: DLG1-AS1 expression was significantly elevated in HeLa/GEM and SiHa/GEM cells. DLG1-AS1 silencing significantly reduced the viability and proliferation of GEM-resistant cervical cancer cells. DLG1-AS1 also promoted GEM sensitivity in cervical cancer cells by inhibiting miR-16-5p. Moreover, the tumor volume in nude mice in the DLG1-AS1 knockdown group decreased after GEM treatment. In addition, DLG1-AS1 targeted miR-16-5p, and miR-16-5p targeted HDGF. The miR-16-5p inhibitor reversed the DLG1-AS1 knockdown effect in GEM-resistant cervical cancer cells. CONCLUSION: Knockdown of DLG1-AS1 promoted GEM sensitivity in cervical cancer cells by regulating miR-16-5p/HDGF.
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MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Desoxicitidina/análogos & derivados , Homólogo 1 de la Proteína Discs Large/genética , Homólogo 1 de la Proteína Discs Large/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , GemcitabinaRESUMEN
OBJECTIVES: The location of the maxillary sinus significantly affects the orthodontic treatment, particularly when temporary anchorage devices (TADs) are taking place. The current study aims to evaluate the maxillary sinus size and location in a skeletal class II population. MATERIALS AND METHODS: The pre-orthodontic treatment CBCT images of the skeletal class II population were selected. The sinus's volumetric size, height, width, and depth were measured and compared among different skeletal vertical patterns and between genders. In addition, the height and width of the alveolar bone surrounding the maxillary sinus floor were quantified in the same manner. RESULTS: Patients who displayed a high-angle skeletal pattern had significantly greater maxillary sinus dimensions, shorter vertical distance between the maxillary sinus floor and the alveolar bone crest, and thinner alveolar bone surrounding the maxillary sinus. Meanwhile, the maxillary sinus dimension measurements were positively correlated with the SN-MP angle in both genders but only correlated with ANB angle in females. On the other hand, the vertical distance between the maxillary sinus floor and the alveolar bone crest was negatively correlated with the SN-MP angle in males but the ANB angle in females. CONCLUSIONS: In the skeletal class II population, the high-angle patients faced a higher risk of maxillary sinus perforations by TADs. In addition, gender-related variations were noticed warranting clinical attention, as males have a higher potential for maxillary sinus penetration from TAD placement than females. CLINICAL RELEVANCE: Maxillary posterior alveolar TADs are often prescribed to achieve the distalization of maxillary posterior teeth in class II patients. The current study provided more insight into the "safe zone" for TAD placement related to the maxillary sinus.
Asunto(s)
Seno Maxilar , Elevación del Piso del Seno Maxilar , Proceso Alveolar/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Maxilar , Seno Maxilar/diagnóstico por imagenRESUMEN
Objective: To analyze sperm function-related risk factors and their value in predicting the fertilization rate (FR) of in vitro fertilization (IVF). METHODS: This retrospective study included 668 cases of IVF performed in the Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology from July 2018 to April 2021, which were divided into a low-FR group (FR ≤ 65%, n = 107) and a high-FR group (FR > 65%, n = 561). We compared the sperm volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), acrosome reaction rate, acrosin activity and DNA fragmentation index (DFI) between the two groups, analyzed the correlation between sperm parameters and FR by Spearman's correlation analysis, and the value of sperm function-related risk factors in predicting the FR of IVF using binary logistic regression analysis and receiver-operator characteristic (ROC) curve. RESULTS: There were statistically significant differences in the infertility type of the female patients (P < 0.05) but not in the sperm volume, sperm concentration, PMS, MNS, and acrosome reaction rate (P > 0.05). The DFI was significantly lower in the high-FR than in the low-FR group (ï¼»14.31 ± 4.46ï¼½% vs ï¼»15.35 ± 5.68ï¼½%, P = 0.034) and the acrosin activity remarkably higher in the former than in the latter group (ï¼»102.11 ± 47.18ï¼½ vs ï¼»91.98 ± 42.61ï¼½ µIU/106, P = 0.039). Spearman's correlation analysis showed that the FR was correlated negatively with DFI (r = 0.090, P = 0.020) and positively with acrosin activity (r = 0.079, P = 0.042). Primary infertility and DFI were found to be unfavorable factors while acrosin activity a favorable factor for the FR of IVF. The areas under the ROC curve (AUC) of DFI and acrosin activity were 0.571 and 0.562, respectively. CONCLUSIONS: DFI and acrosin activity are risk factors and have a predictive value for the fertilization rate of IVF.
RESUMEN
BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge. This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis. METHODS: Clinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed. RESULTS: There was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology (p < 0.050). The lesions in the primary group showed more tentacle-like projections or a "claw" sign, while the lesions in the recurrent group were more commonly oval, lobulated, and irregularly shaped. Hypervascularity was common in both groups. CONCLUSIONS: For primary DFSP, a slow-growing, red nodule on the skin involving the overlying dermis and hypodermis, more frequently a hypoechoic mass with tentacle-like projections or a "claw" sign, was observed. For recurrent DFSP, palpable subcutaneous nodules or subcutaneous masses at the original surgical incision and oval, lobulated, and irregularly shaped lesions were more commonly observed. This may be useful for improving diagnostic accuracy.