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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.
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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.
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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/citologíaRESUMEN
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.
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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 AñoRESUMEN
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.
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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 fármacosRESUMEN
BACKGROUND: Cisplatin-based chemoresistance is major obstacle for breast cancer (BC) including Triple-negative breast cancer (TNBC). SIRT7 is reportedly involved in the progression of BC, the underlining mechanism in Cisplatin-based chemoresistance in BC remains unclear. This work is to elucidate effects of SIRT7 on cisplatin resistance in breast cancer regulated by miR-152-3p. METHODS: The RNA expression of SIRT7 and miRNAs in breast cancer were available from TCGA database. SIRT7-targeted miRNAs were predicted by TargetScan, miRanda, miRDB databases. The association of SIRT7 expression with predicted miRNA was validated by Luciferase assay. Cell apoptosis was determined by Flow cytometry. Cell viability was detected by CCK8 assay. The mRNA expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Protein expression was determined by Western blotting assay. RESULTS: SIRT7 mRNA levels were dramatically enhanced in BC tissues compared to para-carcinoma tissues, also increased in BC patients with Cisplatin-based chemotherapy containing TNBC compared with those without. The increase of SIRT7 expression was obviously relevant to shorter survive time of them. Importantly, SIRT7 inhibition facilitated Cisplatin-induced cell apoptosis of TNBC (MDA-MB-231 and MDA-MB-468) and non- TNBC (MCF-7). Notably, miR-152-3p was predicted as a negative regulator of SIRT7 by overlapping downregulated miRNAs in BC patients treated with Cisplatin-based chemotherapy and miRNAs to target SIRT7. Mechanically, miR-152-3p blocked SIRT7 to stimulate an activation of FOXO3a, cleaved PARP1 and Caspase-3, sensitizing Cisplatin-induced apoptosis of BC cells. CONCLUSIONS: Inhibition of SIRT7 by miR-152-3p may be a promising strategy against the resistance to cisplatin-based chemotherapy in BC containing TNBC.
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Acoustic droplet ejection (ADE) has become the preferred method for liquid transfer in a variety of applications including synthetic biology, genotyping and drug discovery. Comparing with traditional pipetting techniques, the accuracy and data reproducibility of ADE based liquid transfer are improved, waste and cost are reduced, and cross-contamination is eliminated. The key component in the ADE system is the ultrasound transducer, which is responsible for generating focused ultrasound beam for droplet ejection. However, current ADE systems commonly utilize a single-element focused transducer with a fixed focal length that require mechanical movement to focus on the liquid surface, resulting in reduced liquid transfer efficiency. In this study, we first present a high-frequency annular array transducer for the ADE technology, which enables rapid and dynamic axial focusing to the liquid surface without mechanically moving the transducer, thereby accelerating liquid transfer. Experimental results show that the proposed 10 MHz, 5-element annular array transducer has good dynamic axial focusing ability, and can achieve accurate and stable droplet ejection of nanoliter volume at the designed focal length of 26-32 mm. Our results highlight the potential of the annular array transducer in advancing ADE system for rapid liquid transfer. This technology is expected to be useful in a variety of applications where precise and high-throughput liquid transfer is crucial.
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PURPOSE: To create a computational fluid dynamics (CFD) model of ocular anterior segment for primary angle closure diseases (PACD) and assess the aqueous humour (AH) dynamics in different angle closure ranges (ACRs). METHODS: The ocular anterior segment geometry was obtained from an optical coherence tomography image by SOLIDWORKS. Three different angle opening distance at 750 µm from the scleral spur (AOD750) values were established to mimic three widths of anterior chamber angle. The AH dynamics were modelled using the Navier-Stokes equation. The 3D CFD model of the ocular anterior segment was created in COMSOL Multiphysics. The major outcome was the maximum flow velocity (MFV) and pressure in the ocular anterior segment. An in vitro simulation model was used to validate the computational results of the pressure and ACRs. RESULTS: The MFV and pressure both showed a non-linear association with ACR in the CFD models of PACD. The MFV and pressure started to elevate when ACR was larger than 180°, and increased dramatically when the ACR was larger than 270°. The in vitro experiment of the pressure changes was consistent with the CFD model. No significant differences of the MFV and pressure among the three AOD750 models. CONCLUSIONS: The association among the ACR, MFV and pressure is an ascending curve in PACD, and ACR of 180° and 270° are two critical turning points. Our results are consistent with clinical phenomenon and may be used to provide better guidances for the clinical management of PACD in different stages.
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To more accurately diagnose and treat patients with different subtypes of thyroid cancer, we constructed a diagnostic model related to the iodine metabolism of THCA subtypes. THCA expression profiles, corresponding clinicopathological information, and single-cell RNA-seq were downloaded from TCGA and GEO databases. Genes related to thyroid differentiation score were obtained by GSVA. Through logistic analyses, the diagnostic model was finally constructed. DCA curve, ROC curve, machine learning, and K-M analysis were used to verify the accuracy of the model. qRT-PCR was used to verify the expression of hub genes in vitro. There were 104 crossover genes between different TDS and THCA subtypes. Finally, 5 genes (ABAT, CHEK1, GPX3, NME5, and PRKCQ) that could independently predict the TDS subpopulation were obtained, and a diagnostic model was constructed. ROC, DCA, and RCS curves exhibited that the model has accurate prediction ability. K-M and subgroup analysis results showed that low model scores were strongly associated with poor PFI in THCA patients. The model score was significantly negatively correlated with T cell follicular helper. In addition, the diagnostic model was significantly negatively correlated with immune scores. Finally, the results of qRT-PCR corresponded with bioinformatics results. This diagnostic model has good diagnostic and prognostic value for THCA patients, and can be used as an independent prognostic indicator for THCA patients.
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Yodo , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biología Computacional/métodos , Femenino , Masculino , Aprendizaje Automático , Persona de Mediana Edad , Glándula Tiroides/patología , Glándula Tiroides/metabolismo , Curva ROC , Diferenciación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
The objective of this study was to establish a rapid visual diagnosis method for vancomycin-resistant Enterococcus faecium (VREFm) based on multienzyme isothermal rapid amplification (MIRA) combined with lateral flow strips (LFSs). The MIRA primers and probes were specifically designed to maintain the sequence of the VanA gene of VREFm. We optimized the reaction time and temperature and thoroughly assessed the specificity and sensitivity of the MIRA-LFS system. We also compared the MIRA-LFS method with the polymerase chain reaction (PCR) assay and the disc diffusion method. We then evaluated the MIRA-LFS assay for consistency testing and clinical application. The MIRA-LFS technique completed the amplification process within 30 min, and the results were observed on LFS. The method demonstrated high sensitivity, with a minimum detection limit of 1.066 CFU/µL for VREFm and exhibited specificity without cross-reactivity with other pathogenic bacteria. When applied to the detection of clinical samples, the method exhibited consistency with the PCR and agar dilution methods. The combined use of MIRA and LFS in this study facilitates simplifying the workflow for detecting VREFm, which is of great significance for rapidly detecting the enterococcal infections and preventing and controlling the nosocomial infections. IMPORTANCE: One of the key approaches to treating and controlling vancomycin-resistant Enterococcus faecium (VREFm) is an accurate and rapid diagnosis. To achieve this goal, a simple and rapid method must be constructed for immediate detection in the field. Multienzyme isothermal rapid amplification (MIRA) is an isothermal rapid amplification method that allows amplification reactions to be completed under room temperature conditions. When combined with lateral flow strips (LFSs), MIRA-LFS enables the rapid detection of pathogenic microorganisms. However, the MIRA method often produces false signals. These false signals are eliminated by using base mismatches introduced in primers and probes. The MIRA-LFS system was constructed with high specificity and sensitivity for the detection of VREfm, without the limitation of sophisticated instruments. This enables the prompt formulation of diagnostic and therapeutic decisions.
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As a two-dimensional material, gold nanotriangles (GNTs) are rarely studied in the field of gene delivery. In this study, a temperature-responsive GNTs was developed as a novel carrier for gene delivery. The temperature-sensitive copolymer PNIPAm-g-PEI was grafted onto the surface of GNTs to construct a PNIPAm-g-PEI/GNTs composite controllable release platform. The lower critical solution temperature (LCST) of PNIPAm-g-PEI/GNTs was found to be 42 °C, and the particle size of PNIPAm-g-PEI/GNTs was 150 nm at this temperature. Gel electrophoresis experiments showed that PNIPAm-g-PEI/GNTs completely condensed DNA at 20 µg/mL, and PNIPAm-g-PEI/GNTs promoted the release of DNA under laser irradiation. Luciferase and green fluorescent protein reporter gene assays demonstrated that the transfection efficiency of PNIPAm-g-PEI/GNTs was 1.5 and 7.2 times that of PEI, respectively. These results demonstrated the promising potential of temperature-responsive GNTs as effective and safe gene delivery vectors.
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Pulmonary hypertension (PH) is heterogeneous diseases that can lead to death due to progressive right heart failure. Emerging evidence suggests that, in addition to its role in ATP production, changes in mitochondrial play a central role in their pathogenesis, regulating integrated metabolic and signal transduction pathways. This review focuses on the basic principles of mitochondrial redox status in pulmonary vascular and right ventricular disorders, a series of dysfunctional processes including mitochondrial quality control (mitochondrial biogenesis, mitophagy, mitochondrial dynamics, mitochondrial unfolded protein response) and mitochondrial redox homeostasis. In addition, we will summarize how mitochondrial renewal and dynamic changes provide innovative insights for studying and evaluating PH. This will provide us with a clearer understanding of the initial signal transmission of mitochondria in PH, which would further improve our understanding of the pathogenesis of PH.
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OBJECTIVES: To explore the factors associated with poor prognosis in critically ill patients with Electroencephalogram (EEG) patterns exhibiting stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs), and to construct a prognostic prediction model. METHODS: This study included a total of 53 critically ill patients with EEG patterns exhibiting SIRPIDs who were admitted to the First Affiliated Hospital of Chongqing Medical University from May 2023 to March 2024. Patients were divided into two groups based on their Modified Rankin Scale (mRS) scores at discharge: good prognosis group (0-3 points) and poor prognosis group (4-6 points). Retrospective analyses were performed on the clinical and EEG parameters of patients in both groups. Logistic regression analysis was applied to identify the risk factors related to poor prognosis in critically ill patients with EEG patterns exhibiting SIRPIDs; a risk prediction model for poor prognosis was constructed, along with an individualized predictive nomogram model, and the predictive performance and consistency of the model were evaluated. RESULTS: Multivariate logistic regression analysis revealed that APACHE II score (OR=1.217, 95 %CI=1.030â¼1.438), slow frequency bands or no obvious brain electrical activity (OR=8.720, 95 %CI=1.220â¼62.313), and no sleep waveforms (OR=9.813, 95 %CI=1.371â¼70.223) were independent risk factors for poor prognosis in patients. A regression model established based on multivariate logistic regression analysis had an area under the curve of 0.902. The model's accuracy was 90.60 %, with a sensitivity of 92.86 % and a specificity of 89.70 %. The nomogram model, after internal validation, showed a concordance index of 0.904. CONCLUSIONS: A high APACHE II score, EEG patterns with slow frequency bands or no obvious brain electrical activity, and no sleep waveforms were independent risk factors for poor prognosis in patients with SIRPIDs. The nomogram model constructed based on these factors had a favorably high level of accuracy in predicting the risk of poor prognosis and held certain reference and application value for clinical neurofunctional assessment and prognostic determination.
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Electrochemical nitrate reduction to ammonia (ENO3RR) has attracted great attention owing to its characteristics of treating wastewater while producing high value-added ammonia. In this study, we successfully prepared a heterojunction electrocatalyst Fe2O3/ZnO consisting of Fe2O3 nanosheets and ZnO nanoparticles, where the construction of the Fe2O3/ZnO heterojunction not only increased the exposure of the active sites of the catalyst, accelerated the interfacial electron transfer, and improved the conductivity of the catalyst but also optimized its overall electronic structure. Thus, Fe2O3/ZnO demonstrated a high Faraday efficiency of 97.4% and an ammonia yield of 6327.2 µg h-1 cm-2 at -1.0 V (vs. RHE) in 0.1 M KNO3 and 0.1 M PBS. DFT calculations also confirmed that the constructed Fe2O3/ZnO heterojunction effectively decreased the reaction energy barrier of *NO â *NHO and accelerated the reaction kinetics, which is favourable for ENO3RR. This study provides a new and facile design strategy of catalysts for electrochemical nitrate reduction to ammonia.
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In this work, etonogestrel implants were manufactured using coextrusion. The purpose of the study was to correlate changes in microstructure and transport properties that occurred in etonogestrel implants to drug release mechanisms. The implants consisted of an EVA 28 (28% vinyl acetate) core containing dispersed and dissolved etonogestrel, and an EVA 15 (15% vinyl acetate) skin. The drug release was determined to be via diffusion at a controlled rate and governed by implant dimensions. In-vitro release revealed evidence of supersaturation in the implant core and skin, likely from the intense mechanical energy input during the twin-screw manufacturing process. Subsequently during storage under ambient conditions, supersaturation resulted in recrystallization of drug crystals, preferentially in the implant core. Etonogestrel solubility and diffusivity in EVA were determined by permeation experiments and used for release modeling. Drug release from the EVA skin layer deviated from the predicted values due to 1) formation of a drug depletion zone in the core and 2) presence of a stagnant media layer adjacent to the skin. Drug release from implant ends was significantly faster than predicted. Air-filled pores were observed in the implant core using microCT which likely contributed to the faster release from implant ends.
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Sunlight has long served as primary energy source on our planet, shaping the behavior of living organisms. Extensive research has been dedicated to unraveling the evolutionary pathways involved. When the formation of Earth atmosphere, it primarily consisted of small gas molecules, which are considered crucial for the emergence of life. Recent demonstrations have shown that these molecules can also be transformed into semiconductors, with the potential to harness solar energy and catalyze chemical reactions as photocatalysts. Building upon this research, this minireview focuses on the potential revolutionary impact of photocatalysis on Earth. Initially, it examines key reactions, such as the formation of prebiotic molecules and the oxygen evolution reaction via water oxidation. Additionally, various C-N complexes in photocatalysts are explored, showcasing their roles in catalyzing chemical reactions. The conclusion and outlook provide a potential pathway for the evolution of Earth, shedding light on the significance of metal-free photocatalysts in development of Earth.
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We present the first robot-assisted transcatheter mitral edge-to-edge repair (M-TEER) for the treatment of severe mitral regurgitation. 68-year-old patient presented with worsening dyspnea on exertion and intermittent palpitations (NYHA class III). Transthoracic echocardiography revealed severe functional mitral regurgitation (MR) with moderate left ventricular and left atrial enlargement. Due to the patient's high surgical risk (STS score of 8.84%), a transcatheter mitral edge-to-edge repair was planned following heart team discussion. Results: The final transesophageal echocardiography confirmed that the MR had reduced from the original severe to mild. This case report demonstrates, the feasibility of a mitral TEER system with a robotic-assisted approach, potentially paving the way for future applications in structural heart and endovascular intervention.
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BACKGROUND: Lung abscess found on chest X-ray and computed tomography examinations is rare in infants and young children. Several pathogens can cause lung abscesses, with the most common pathogens being anaerobes, Streptococci and Staphylococcus aureus. Streptococcus pseudopneumoniae (S. pseudopneumoniae) is a member of the Streptococcaceae family, and is mainly isolated from respiratory tract specimens. There are currently no cases of lung abscess caused by S. pseudopneumoniae in the literature. CASE SUMMARY: A 2-year-old boy was admitted to hospital due to persistent cough and fever. Lung computed tomography examination suggested the formation of a lung abscess. His diagnosis was not confirmed by testing for serum respiratory pathogens (6 items), respiratory pathogen nucleic acid (27 items), and laboratory culture. Finally, metagenomic next-generation sequencing of bronchoalveolar lavage fluid revealed the presence of S. pseudopneumoniae, confirming its role in causing the lung abscess. After receiving antibiotic treatment, reexamination with lung computed tomography showed that the abscess was resorbed and the patient's outcome was good. CONCLUSION: This is the first report of a lung abscess in a child caused by S. pseudopneumoniae infection. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid is helpful in achieving rapid and accurate pathogen identification.
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Background: The demand for fertility-sparing surgery (FSS) is increasing among patients with early-stage cervical cancer (CC). This study aimed to evaluate the feasibility of local excision as an alternative to hysterectomy in stage I CC patients aged 15-39 years-commonly referred to as adolescents and young adults (AYAs)-with varying clinicopathological characteristics. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed between 2000 and 2020. We examined treatment interventions across different age groups, degrees of histological types, tumor differentiation, and tumor stages. The effect of local excision vs. hysterectomy was assessed by comparing overall survival (OS) and disease-specific survival (DSS) rates. Results: A total of 10,629 stage I AYA cervical cancer patients were included in this study. Among these patients, 24.5% underwent local excision for fertility preservation, while 67.3% underwent radical hysterectomy. For patients with cervical squamous cell carcinoma (SCC), long-term outcomes favored local excision over hysterectomy, and a similar trend was observed in those with adenosquamous cell carcinoma (ASCC). However, the prognosis was comparable among patients with cervical adenocarcinoma (AC). In patients with well- and moderate- differentiated tumors, local excision demonstrated superior OS compared to hysterectomy. No significant differences in prognosis were found between the two surgical interventions for patients with poorly differentiated and undifferentiated tumors. In stage IA patients, local excision was considered a viable alternative to hysterectomy. In stage IB1-IB2, FSS yielded prognostic outcomes comparable to those of hysterectomy. Conversely, patients with stage IB3 exhibited significantly shorter 5-year OS and DSS following local excision than those who underwent hysterectomy. Conclusion: In stage IA-IB2 (diameter ≤4â cm) AYA patients, local excision may serve as a viable option for fertility preservation. The histological type of SCC, AC, and ASCC, along with differentiation, should not serve as restrictive factors in determining fertility preservation strategies for these patients. Patients with early-stage, well- or moderately-differentiated SCC may benefit from local excision surgery, even when fertility preservation is not the primary objective.
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Rationale: Understanding the immune mechanisms associated with liver transplantation (LT), particularly the involvement of tissue-resident memory T cells (TRMs), represents a significant challenge. Methods: This study employs a multi-omics approach to analyse liver transplant samples from both human (n = 17) and mouse (n = 16), utilizing single-cell RNA sequencing, bulk RNA sequencing, and immunological techniques. Results: Our findings reveal a comprehensive T cell-centric landscape in LT across human and mouse species, involving 235,116 cells. Notably, we found a substantial increase in CD8+ TRMs within rejected grafts compared to stable ones. The elevated presence of CD8+ TRMs is characterised by a distinct expression profile, featuring upregulation of tissue-residency markers (CD69, CXCR6, CD49A and CD103+/-,), immune checkpoints (PD1, CTLA4, and TIGIT), cytotoxic markers (GZMB and IFNG) and proliferative markers (PCNA and TOP2A) during rejection. Furthermore, there is a high expression of transcription factors such as EOMES and RUNX3. Functional assays and analyses of cellular communication underscore the active role of CD8+ TRMs in interacting with other tissue-resident cells, particularly Kupffer cells, especially during rejection episodes. Conclusions: These insights into the distinctive activation and interaction patterns of CD8+ TRMs suggest their potential utility as biomarkers for graft rejection, paving the way for novel therapeutic strategies aimed at enhancing graft tolerance and improving overall transplant outcomes.
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Linfocitos T CD8-positivos , Rechazo de Injerto , Trasplante de Hígado , Células T de Memoria , Análisis de la Célula Individual , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Humanos , Rechazo de Injerto/inmunología , Animales , Ratones , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Memoria Inmunológica , Masculino , Ratones Endogámicos C57BL , Antígenos CD/metabolismo , Antígenos CD/genética , Femenino , Persona de Mediana Edad , Proteínas de Dominio T BoxRESUMEN
Background: Protein information is often replaced by RNA data in studies to understand cancer-related biological processes or molecular functions, and proteins of prognostic significance in Kidney clear cell carcinoma (KIRC) remain to be mined. Methods: The cancer genome atlas program (TCGA) data was utilized to screen for proteins that are prognostically significant in KIRC. Machine learning algorithms were employed to develop protein prognostic models. Additionally, immune infiltration abundance, somatic mutation differences, and immunotherapeutic responses were analyzed in various protein risk subgroups. Ultimately, the validation of protein-coding genes was confirmed by utilizing an online database and implementing quantitative real-time PCR (qRT-PCR). Results: The patients were divided into two risk categories based on prognostic proteins, and notable disparities in both overall survival (OS) and progression free interval (PFI) were observed between the two groups. The OS was more unfavorable in the high-risk group, and there was a noteworthy disparity in the level of immune infiltration observed between the two groups. In addition, the nomogram showed high accuracy in predicting survival in KIRC patients. Conclusion: In this research, we elucidated the core proteins associated with prognosis in terms of survival prediction, immunotherapeutic response, somatic mutation, and immune microenvironment. Additionally, we have developed a reliable prognostic model with excellent predictive capabilities.