RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear. AIM OF THE STUDY: The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting. MATERIALS AND METHODS: We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them. In addition, we evaluated the effects of SJD on the cyclic guanosine monophosphate-adenosine monophosphate synthase -stimulator of interferon genes (cGAS-STING) and inflammasome by immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: We demonstrated that SJD was effective in alleviating LPS-induced ALI by suppressing the levels of pro-inflammatory cytokines in the BALF, improving the level of lung histopathology and the number of neutrophils, as well as decreasing the inflammatory factor-associated gene expression. Importantly, we found that SJD could inhibit multiple stimulus-driven activation of cGAS-STING and inflammasome. Further studies showed that the Chinese herbal medicines in SJD had no influence on the cGAS-STING pathway and inflammasome alone at the formulated dose. By increasing the concentration of these herbs, we observed inhibitory effects on the cGAS-STING pathway and inflammasome, and the effect exerted was maximal when the six herbs were combined, indicating that the synergistic effects among these herbs plays a crucial role in the anti-inflammatory effects of SJD. CONCLUSIONS: Our research demonstrated that SJD has a favorable protective effect against ALI, and its mechanism of effect may be associated with the synergistic effect exerted between six Chinese medicines to inhibit the cGAS-STING and inflammasome abnormal activation. These results are favorable for the wide application of SJD in the clinic as well as for the development of drugs for ALI from herbal formulas.

Asunto(s)

Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Inflamasomas , Lipopolisacáridos , Proteínas de la Membrana , Nucleotidiltransferasas , Transducción de Señal , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lipopolisacáridos/toxicidad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Nucleotidiltransferasas/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones , Masculino , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Modelos Animales de Enfermedad , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Líquido del Lavado Bronquioalveolar/citología

RESUMEN

In this study, the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities, sludge characteristics and microbial communities were investigated. The increase in salinity resulted in a decrease in particle size of the granular sludge, which was concentrated in the range of 0.5-1.0 mm. The content of EPS (extracellular polymeric substances) in the granular sludge gradually increased with increasing salinity and the addition of betaine (a typical compatible solute). Meanwhile, the microbial community structure was significantly affected by salinity, with high salinity reducing the diversity of bacteria. At higher salinity, Patescibacteria and Proteobacteria gradually became the dominant phylum, with relative abundance increasing to 13.53% and 12.16% at 20 g/L salinity. Desulfobacterota and its subordinate Desulfovibrio, which secrete EPS in large quantities, dominated significantly after betaine addition.Their relative abundance reached 13.65% and 7.86% at phylum level and genus level. The effect of these changes on the treated effluent was shown as the average chemical oxygen demand (COD) removal rate decreased from 82.10% to 79.71%, 78.01%, 68.51% and 64.55% when the salinity gradually increased from 2 g/L to 6, 10, 16 and 20 g/L. At the salinity of 20 g/L, average COD removal increased to 71.65% by the addition of 2 mmol/L betaine. The gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment, which provided a feasible strategy for anaerobic treatment of organic saline wastewater.

Asunto(s)

Betaína , Salinidad , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas Residuales , Betaína/metabolismo , Aguas del Alcantarillado/microbiología , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Anaerobiosis , Microbiota/efectos de los fármacos , Bacterias/metabolismo , Bacterias/efectos de los fármacos

RESUMEN

Size-fractionated particulate matter (PM2.5 and PM>2.5) was collected at a traffic site in Kanazawa, Japan in a seasonal sampling work in 2020. Nine polycyclic aromatic hydrocarbons (4- to 6-ring PAHs) were determined in fine and coarse particles. The gas/particle partitioning coefficients (Kp) of the PAHs were calculated from the supercooled liquid vapour pressure and octanol-air partitioning coefficient based on the relationships obtained in previous traffic pollution-related studies. Gaseous PAHs were estimated by Kp and the concentrations of PM and particulate PAHs. The concentrations of total PAHs were 32.5, 320.1 and 5646.2 pg/m3 in the PM>2.5, PM2.5 and gas phases, respectively. Significant seasonal trends in PAHs were observed (particle phase: lowest in summer, gas phase: lowest in spring, particle and gas phase: lowest in spring). Compared to 2019, the total PAH concentrations (in particles) decreased in 2020, especially in spring and summer, which might be due to reduced traffic trips during the COVID-19 outbreak. The incremental lifetime cancer risk (ILCR) calculated from the toxic equivalent concentrations relative to benzo[a]pyrene (BaPeq) was lower than the acceptable limit issued by the US Environmental Protection Agency, indicating a low cancer risk in long-term exposure to current PAH levels. It is notable that gaseous PAHs considerably contributed to BaPeq and ILCR (over 50%), which highlighted the significance of gaseous PAH monitoring for public health protection. This low-cost estimation method for gaseous PAHs can be expected to reliably and conveniently obtain PAH concentrations as a surrogate for traditional sampling in the future work.

Asunto(s)

Contaminantes Atmosféricos , Monitoreo del Ambiente , Material Particulado , Hidrocarburos Policíclicos Aromáticos , Hidrocarburos Policíclicos Aromáticos/análisis , Japón , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Material Particulado/análisis , Emisiones de Vehículos/análisis , Estaciones del Año

RESUMEN

Background: Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored. Methods: A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. Results: A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15-0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01-2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease. Conclusions: Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

RESUMEN

SETD3 is a member of SET domain-containing proteins. It has been discovered as the first metazoan protein (actin) histidine methyltransferase. In addition to this well-characterized molecular function of SETD3, it has been clearly shown to be involved in multiple biological processes, such as cell differentiation, tumorigenesis and viral infection. Here, we summarize the current knowledge on the roles of SETD3 beyond its histidine methyltransferase activity, and outline its cellular and molecular modes of action, as well as the upstream regulation on SETD3, therefore providing insights for the molecular basis of how SETD3 fine regulates multiple physiological and pathological processes.

RESUMEN

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints.

Asunto(s)

Artritis Reumatoide , Macrófagos , Nanopartículas , Animales , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Nanopartículas/química , Células RAW 264.7 , Masculino , Ratones Endogámicos DBA , Artritis Experimental/tratamiento farmacológico , Compuestos de Boro/química , Compuestos de Boro/farmacología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Humanos , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos

RESUMEN

Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.

RESUMEN

Objective: Preoperative diagnosis for follicular thyroid cancer (FTC) remains challenging. The purpose of this study was to explore the maximum intensity projection (MIP) features, which can be utilized for reconstructing and characterizing the structure of microvascular in tissue, associated with FTC, and to explore the independent risk factors for FTC in combination with multimodal ultrasonography and blood indicators. Methods: This single-center, prospective, single-blind, observational study included patients with suspected follicular thyroid carcinoma based on preoperative ultrasonography findings. All patients underwent routine ultrasonography, contrast-enhanced ultrasonography (CEUS), and correlated blood indexes tests. Offline MIP reconstruction of the CEUS images was performed. The tumor was histologically diagnosed postoperatively. Multivariable logistics regression was utilized for analyzing MIP characteristics combined with multimodal ultrasonography and preoperative blood indicators to identify independent risk factors for FTC. Results: In this study, 61 thyroid nodules were finally included according to the atretic criteria. (1) Compared with traditional color profile ultrasonography and CEUS, MIP technology can provide more information regarding microvascular characteristics inside thyroid tumors. The short, rod-like, crossed, curved and firework-like features of MIP images revealed statistically significant differences between the benign and malignant groups. (2) Multivariable logistic regression analysis indicated that the firework-like MIP characteristics of microvascular, thyroglobulin (Tg) level and vessel intensity (VI) value were independent risk factors for malignancy. Conclusion: (1) MIP technology has potential applications in the differential diagnosis of follicular thyroid carcinoma from benign lesions. (2) Firework MIP microvascular characteristics, Tg values and VI values can serve as parameters for the differential diagnosis of follicular thyroid carcinoma from benign lesions. This study provides a novel approach idea for preoperative multimodal differentiation of follicular thyroid carcinoma from benign lesions.

RESUMEN

Osteosarcoma, the most prevalent malignant bone tumor, is notorious for its aggressive growth and invasiveness. The highly mutable genome of osteosarcoma has made identifying a key oncogene challenging, hindering the development of targeted treatments. Our study validates the effectiveness of XD23, an anti-cancer agent we previously identified, in curbing osteosarcoma proliferation, metastasis, EMT differentiation, and bone destruction and promoting osteosarcoma apoptosis. It further elucidated that XD23 thwarts osteosarcoma by suppressing DKK1 expression, which in turn activates the WNT-ß/Catenin pathway. This research presents the concrete evidence of DKK1's involvement in osteosarcoma development, offering a foundation for the development of DKK1 inhibitors as novel treatments for this disease.

RESUMEN

Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2 µg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50 nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48 h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.

RESUMEN

Objective: To construct an interpretation structure model of adverse experiences of cardiac surgery patients in intensive care unit, so as to provide a reference for optimizing the experience of critical patients step by step. Methods: Literature review, semi-structured interviews, questionnaires and Delphi method were used to summarize and analyze the influencing factors of intensive care experience in cardiac surgery. The explanatory structural model was used to divide the influencing factors into levels and construct the explanatory structural model of adverse experience of cardiac surgery patients in intensive care. Results: A hierarchical structure model containing 34 elements and 15 levels was constructed, which were divided into Surface level, middle level and root level. Conclusion: The intensive care experience of patients in cardiac surgery department is mainly affected by 34 factors. There are direct or indirect correlations between the influencing factors, and different levels have different effects.

RESUMEN

Acute lung injury (ALI) is one of the most deadly and prevalent diseases in the intensive care unit. Ferroptosis and mitophagy are pathological mechanisms of ALI. Ferroptosis aggravates ALI, whereas mitophagy regulates ALI. Ferroptosis and mitophagy are both closely related to reactive oxygen species (ROS). Mitophagy can regulate ferroptosis, but the specific relationship between ferroptosis and mitophagy is still unclear. This study summarizes previous research findings on ferroptosis and mitophagy, revealing their involvement in ALI. Examining the functions of mTOR and NLPR3 helps clarify the connection between ferroptosis and mitophagy in ALI, with the goal of establishing a theoretical foundation for potential therapeutic approaches in the future management of ALI.

Asunto(s)

Lesión Pulmonar Aguda , Ferroptosis , Mitofagia , Especies Reactivas de Oxígeno , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Ferroptosis/fisiología , Humanos , Especies Reactivas de Oxígeno/metabolismo , Animales , Serina-Treonina Quinasas TOR/metabolismo

RESUMEN

Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt's disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber's congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber's congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.

Asunto(s)

Portadores de Fármacos , Humanos , Animales , Portadores de Fármacos/química , Inyecciones Intraoculares , Retina , Enfermedades de la Retina/terapia , Enfermedades de la Retina/tratamiento farmacológico , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Degeneración Macular/terapia

RESUMEN

Kainic acid (KA)-induced excitotoxicity induces acute degradation of phospholipids and release of free fatty acids (FFAs) in rodent hippocampus, but the long-term changes in phospholipids or the subcellular origins of liberated FFAs remain unclarified. Phospholipids and FFAs were determined in KA-damaged mouse hippocampus by enzyme-coupled biochemical assays. The evolution of membrane injuries in the hippocampus was examined by a series of morphological techniques. The levels of phospholipids in the hippocampus decreased shortly after KA injection but recovered close to the control levels at 24 h. The decline in phospholipids was accelerated again from 72 to 120 after KA treatment. The levels of FFAs were negatively related to those of phospholipids, exhibiting a similar but opposite trend of changes. KA treatment caused progressively severe damage to vulnerable neurons, which was accompanied by increased permeability in the cell membrane and increased staining of membrane-bound dyes in the cytoplasm. Double fluorescence staining showed that the latter was partially overlapped with abnormally increased endocytic and autophagic components in damaged neurons. Our results revealed intricate and biphasic changes in phospholipid and FFA levels in KA-damaged hippocampus. Disrupted endomembrane system may be one of the major origins for KA-induced FFA release.

RESUMEN

Introduction: The identification of risk factors for regional lymph node (r-LN) metastasis in rectal neuroendocrine tumors (R-NETs) remains challenging. Our objective was to investigate the risk factors associated with patients diagnosed with R-NETs exhibiting r-LN metastasis. Methods: Patient information was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, complemented by data from the West China Hospital (WCH) databases. The construction cohort comprised patients diagnosed with R-NETs from the SEER database, while cases from the WCH database were utilized as the validation cohort. A novel nomogram was developed to predict the probability of r-LN metastasis, employing a logistic regression model. Results: Univariate analysis identified four independent risk factors associated with poor r-LN metastasis: age (HR = 1.027, p < 0.05), grade (HR = 0.010, p < 0.05), T stage (HR = 0.010, p < 0.05), and tumor size (HR = 0.005, p < 0.05). These factors were selected as predictors for nomogram construction. Discussion: The novel nomogram serves as a reliable tool for predicting the risk of r-LN metastasis, providing clinicians with valuable assistance in identifying high-risk patients and tailoring individualized treatments.

RESUMEN

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration, destruction, and excessive ossification of articular cartilage. The prevalence of OA is rising annually, concomitant with the aging global population and increasing rates of obesity. This condition imposes a substantial and escalating burden on individual health, healthcare systems, and broader social and economic frameworks. The etiology of OA is multifaceted and not fully understood. Current research suggests that the death of chondrocytes, encompassing mechanisms such as cellular apoptosis, pyroptosis, autophagy, ferroptosis and cuproptosis, contributes to both the initiation and progression of the disease. These cell death pathways not only diminish the population of chondrocytes but also exacerbate joint damage through the induction of inflammation and other deleterious processes. This paper delineates the morphological characteristics associated with various modes of cell death and summarizes current research results on the molecular mechanisms of different cell death patterns in OA. The objective is to review the advancements in understanding chondrocyte cell death in OA, thereby offering novel insights for potential clinical interventions.

Asunto(s)

Muerte Celular , Condrocitos , Progresión de la Enfermedad , Osteoartritis , Condrocitos/patología , Humanos , Osteoartritis/patología , Osteoartritis/terapia , Muerte Celular/fisiología , Apoptosis/fisiología , Cartílago Articular/patología , Autofagia/fisiología , Animales , Piroptosis/fisiología , Ferroptosis/fisiología

RESUMEN

RATIONALE: Tachycardia is a common arrhythmia in clinical practice, and its pathogenesis is mostly related to reentry. However, there are also a few tachycardia that are not related to reentry. Actively clarifying the pathogenesis of these non-reentry related tachycardia is of great significance for its treatment. PATIENT CONCERNS: A 55-year-old female patient presented with recurrent palpitations with a fastest heart rate of 180 beats/minute 10 years ago. DIAGNOSIS: Dual atrioventricular nodal non-reentrant tachycardia (DAVNNT). INTERVENTIONS: DAVNNT can be cured by radiofrequency ablation of atrioventricular nodal slow path modification. OUTCOMES: The tachycardia has stopped. CONCLUSION: DAVNNT is a rare disease in clinical practice. Its characteristic is not reentration-related arrhythmias, but the phenomenon of increased heart rate caused by electrical conduction down the double pathway of atrioventricular nodal tract and subsequent pathway. Electrophysiological examination helps to clarify the diagnosis and pathogenesis, and catheter ablation can cure the disease.

Asunto(s)

Ablación por Catéter , Humanos , Femenino , Persona de Mediana Edad , Ablación por Catéter/métodos , Taquicardia por Reentrada en el Nodo Atrioventricular/diagnóstico , Taquicardia por Reentrada en el Nodo Atrioventricular/cirugía , Taquicardia por Reentrada en el Nodo Atrioventricular/fisiopatología , Electrocardiografía , Nodo Atrioventricular/fisiopatología , Nodo Atrioventricular/cirugía

RESUMEN

The successful pulmonary metastasis of malignant cancer cells depends on the survival of circulating tumor cells in a distant and hostile microenvironment. The formation of a pre-metastatic niche (PMN) creates a supportive environment for subsequent metastasis. Circular RNAs (circRNAs) are increasingly acknowledged as crucial elements in the mechanisms of metastasis due to their stable structures and functions, making them promising early metastasis detection markers. However, the specific expression patterns and roles of circRNAs in the lungs before metastasis remain largely unexplored. Our research aims to chart the circRNA expression profile and assess their impact on the lung PMN. We developed a lung PMN model and employed comprehensive RNA sequencing to analyze the differences in circRNA expression between normal and pre-metastatic lungs. We identified 38 significantly different circRNAs, primarily involved in metabolism, apoptosis, and inflammation pathways. We then focused on one specific circRNA, circ:chr4:150406196 - 150406664 (circRERE-PMN), which exhibited a significant change in expression and was prevalent in myeloid-derived suppressor cells (MDSCs), alveolar epithelial cells, and macrophages within the pre-metastatic lung environment. CircRERE-PMN was found to potentially regulate apoptosis and the expression of cytokines and chemokines through its interaction with the downstream target HUR in alveolar epithelial cells. Overall, our study highlights the crucial role of circRNAs in the formation of lung PMNs, supporting their potential as diagnostic or therapeutic targets for lung metastasis.

Asunto(s)

Neoplasias Pulmonares , ARN Circular , ARN Circular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Animales , Ratones , Humanos , Microambiente Tumoral , Pulmón/patología , Pulmón/metabolismo , Apoptosis/genética , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Transcriptoma , Metástasis de la Neoplasia , Citocinas/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología

RESUMEN

The connectivity reliability of strait and canal nodes in seaborne crude oil networks is uncertain because of various risk factors. Existing studies have mainly focused on road networks and often ignored real-world factors by assuming fixed and identical values for the connectivity reliability of each node, leading to inaccurate estimations. Few studies have considered node reliability when identifying the most reliable routes for oil shipments in response to various external and changing risks. To address these limitations, we first establish new connectivity reliability evaluation methods for both nodes and networks. Then, we develop the α-most reliable shipping route and the very most reliable shipping route models using uncertain programming to dynamically identify the most reliable routes for crude oil, ensuring timely and safe transportation. We apply these models to China's seaborne network of imported crude oil. The results show a network connectivity reliability of 0.6228, which is impacted by unreliable origin-destination pairs in the Middle East. The risk values of the most reliable oil shipping routes vary regionally, with higher values in Africa and the Middle East than in Asia and Latin America. As node risk increases, regional disparities also increase. These findings will aid in the development of energy transportation and import strategies to enhance transportation reliability.

RESUMEN

Background: Previous studies have highlighted the crucial role of Wnt7B in the development of various cancers, including breast, pancreatic, and gastric cancers. However, research into the involvement of Wnt7B is often confined to specific tumor types, with a noticeable lack of comprehensive studies spanning multiple cancer forms. The potential of Wnt7B as a diagnostic or prognostic cancer biomarker has not been fully explored. Methods: In this study, we combined bioinformatics and immunohistochemistry analyses to examine the expression patterns and functions of Wnt7B in cancerous and adjacent noncancerous tissues across a range of tumors. Results: Our data indicate that Wnt7B may serve as a novel prognostic biomarker and therapeutic target in certain cancers. Conclusion: We found significant upregulation of Wnt7B expression levels in the majority of cancer cases examined. Furthermore, Wnt7B can influence cancer prognosis by modulating the tumor microenvironment, immune cell infiltration, and tumor stemness, among other factors. Additionally, we examined the associations between anticancer drug sensitivity and Wnt7B expression, which could aid in the development of more precise clinical therapies.