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Exosomes play a crucial role in regulating extracellular communication between normal and cancer cells within the tumor microenvironment, thereby affecting tumor progression through their cargo molecules. However, the specific impact of exosomal circular RNAs (circRNAs) on the development of cadmium-induced carcinogenesis remains unclear. To address this, we investigated whether exosomes derived from normal human bronchial epithelial BEAS-2B (N-B2B) cells could transmit circRNA to cadmium-transformed BEAS-2B (Cd-B2B) cells and the potential effects on Cd-B2B cells. Our findings demonstrated a significant downregulation of circ_0004664 in Cd-B2B cells compared to N-B2B cells (P < 0.01). Overexpression of circ_0004664 in Cd-B2B cells led to a significant inhibition of cell migration and invasion (P < 0.01 or P < 0.05). Furthermore, N-B2B cells could transfer circ_0004664 into recipient Cd-B2B cells via exosomes, subsequently inhibiting cell migration and invasion (P < 0.05 or P < 0.01). Mechanistic investigations revealed that exosomal circ_0004664 functioned as a competitive endogenous RNA for miR-942-5p, resulting in an upregulation of PTEN (P < 0.05). Our study highlights the involvement of exosomal circ_0004664 in cell-cell communication during cadmium carcinogenesis, providing a novel insight into the role of exosomal circRNA in this process.
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Influenza B viruses (IBVs) primarily infect humans and are a common cause of respiratory infections in humans. Here, to systematically analyze the antigenicity of the IBVs Hemagglutinin (HA) protein, 31 B/Victoria and 19 B/Yamagata representative circulating strains were selected from Global Initiative of Sharing All Influenza Data (GISAID), and pseudotyped viruses were constructed with the vesicular stomatitis virus system. Guinea pigs were immunized with three doses of vaccines (one dose of DNA vaccines following two doses of pseudotyped virus vaccines) of the seven IBV vaccine strains, and neutralizing antibodies against the pseudotyped viruses were tested. By comparing differences between various vaccine strains, we constructed several pseudotyped viruses that contained various mutations based on vaccine strain BV-21. The vaccine strains showed good neutralization levels against the epidemic virus strains of the same year, with neutralization titers ranging from 370 to 840, while the level of neutralization against viruses prevalent in previous years decreased 1-10-fold. Each of the high-frequency epidemic strains of B/Victoria and B/Yamagata not only induced high neutralizing titers, but also had broadly neutralizing effects against virus strains of different years, with neutralizing titers ranging from 1000 to 7200. R141G, D197N, and R203K were identified as affecting the antigenicity of IBV. In this study, pseudotyped virus system was used to monitor the cross-neutralizing efficacy of high-frequency epidemic strains and vaccine strains recommended by the World Health Organization. Additionally, we identified three mutation sites that can seriously affect the antigenicity of B/Victoria vaccine strains. These mutation sites provide valuable references for the selection and design of a universal IBV vaccine strain in the future.
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BACKGROUND: Umbilical cord blood (UCB) is a rich source of multifunctional stem cells characterized by low immunogenicity. Recent research in the fields of aging and regenerative medicine has revealed the potential of human umbilical cord blood-derived exosomes (UCB-Exos) in promoting wound healing, anti-aging, and regeneration. However, their role in neurodegenerative diseases, specifically Parkinson's disease (PD), remains unexplored. This study investigates the potential therapeutic effects and underlying mechanisms of UCB-Exos on PD. METHODS: Large extracellular vesicles (LEv), Exos, and soluble fractions (SF) of human UCB plasma were extracted to investigate their effects on motor dysfunction of the MPTP-induced PD mouse model and identify the key components that improve PD symptoms. UCB-Exos were administered by the caudal vein to prevent or treat the PD mouse model. The motor function and pathological markers were detected. Differentially expressed gene and KEGG enrichment pathways were screened by transcriptome sequence. MN9D and SH-SY5Y cells were cultured and evaluated for cell viability, oxidative stress, cell cycle, and aging-related indexes by qRT-PCR, western blot, immunofluorescence, and flow cytometry. The protein expression level of the MAPK p38 and ERK1/2 signaling pathway was detected by western blot. RESULTS: We observed that LEv, Exos, and SF all exhibited potential in ameliorating motor dysfunction in MPTP-induced PD model mice, with UCB-Exos demonstrating the most significant effect. UCB-Exos showed comparable efficacy in preventing and treating motor dysfunction, cognitive decline, and substantia nigra pathological damage in PD mice. Further investigations revealed that UCB-Exos could potentially alleviate oxidative damage, aging and degeneration, and energy metabolism disorders in neurons. Transcriptome sequencing results corroborated that genes differentially expressed due to UCB-Exos were primarily enriched in the neuroactive ligand-receptor interaction, Dopaminergic synapse, and MAPK signaling pathway. We also observed that UCB-Exos significantly inhibited the hyperphosphorylation of the MAPK p38 and ERK1/2 signaling pathways both in vitro and in vivo. CONCLUSIONS: Our study provides a comprehensive evaluation of UCB-Exos on the neuroprotective effects and suggests that inhibition of hyperphosphorylation of MAPK p38 and ERK 1/2 signaling pathways by regulating transcription levels of HspB1 and Ppef2 may be the key mechanism for UCB-Exos to improve PD-related pathological features.
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Modelos Animales de Enfermedad , Neuronas Dopaminérgicas , Exosomas , Sangre Fetal , Ratones Endogámicos C57BL , Enfermedad de Parkinson , Animales , Exosomas/metabolismo , Neuronas Dopaminérgicas/metabolismo , Ratones , Humanos , Enfermedad de Parkinson/metabolismo , Sangre Fetal/citología , Masculino , Estrés Oxidativo , Sistema de Señalización de MAP Quinasas , Vesículas Extracelulares/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Línea CelularRESUMEN
Background: Immune checkpoint blockade (ICB)-based immunotherapy has inspired new hope for advanced biliary tract cancer (BTC) treatment; however, there are no prior studies that primarily focus on different anatomical types of unresectable BTCs reacting differently to ICB. Methods: We retrospectively collected data on advanced BTC patients who received anti-programmed cell death protein 1 (anti-PD1) therapy from two affiliated hospitals of Sun Yat-Sen university. The effects of anti-PD1 were compared for different anatomical sites. The GSE32225 and GSE132305 datasets were used to further analyze differences in the immune microenvironments between intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Results: A total of 198 advanced BTC patients were enrolled in this study, comprising 142 patients with ICC and 56 with other cancer types ("Others" group), including ECC and gallbladder cancer. In the anti-PD1 treated patients, the ICC group (n = 90) achieved longer median progression-free survival (mPFS) (9.5 vs. 6.2 months, p = 0.02) and median overall survival (mOS) (15.1 vs. 10.7 months, p = 0.02) than the Others group (n = 26). However, chemotherapy did not show different effects between the two groups (mOS: 10.6 vs. 12.1 months, p = 0.20; mPFS: 4.9 vs. 5.7 months, p = 0.83). For the first-line anti-PD1 therapy, the ICC group (n = 70) achieved higher mOS (16.0 vs. 11.8 months, p = 0.04) than the Others group (n = 19). Moreover, most chemokines, chemokine receptors, major histocompatibility complex molecules, immunostimulators, and immunoinhibitors were stronger in ICC than ECC; furthermore, CD8+ T cells and M1 macrophages were higher in ICC than ECC for most algorithms. The immune differential genes were mainly enriched in antigen processing and presentation as well as the cytokine receptors. Conclusions: This study shows that the efficacy of anti-PD1 therapy was higher in ICC than in other types of BTCs. Differences in the immune-related molecules and cells between ICC and ECC indicate that ICC could benefit more from immunotherapy.
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Al-Mg alloys are widely used as important engineering structural materials in aerospace engineering, transportation systems, and structural constructions due to their low density, high specific strength, corrosion resistance, welding capability, fatigue strength, and cost-effectiveness. However, the conventional Al-Mg alloys can no longer fully satisfy the demands of practical production due to difficulties caused by many defects. The high strength of Al-Mg alloys as non-heat treatment precipitation-strengthened alloys is achieved primarily by solid solution strengthening along with work hardening rather than precipitation strengthening. Therefore, severe plastic deformation (SPD) techniques can be often used to produce ultrafine-grained structures to fabricate ultra-high strength aluminum alloys. However, this approach often achieves the strengthening of material at the cost of reduced ductility. This paper comprehensively summarizes the various approaches of ultrafine/nanocrystalline materials for enhancing their plasticity, elaborates on the creation of a bimodal microstructure within the alloy, and discusses the formation of a nanotwin microstructure within the alloy and the incorporation of dispersed nanoparticles. The mechanisms underlying both the strengthening and toughening during large plastic deformation in aluminum alloys are summarized, and the future research direction of high-performance ultrafine crystalline and nanocrystalline Al-Mg aluminum alloys is prospected.
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MOTIVATION: Learning cellular dynamics through reconstruction of the underlying cellular potential energy landscape (aka Waddington landscape) from time-series single-cell RNA sequencing (scRNA-seq) data is a current challenge. Prevailing data-driven computational methods can be hampered by the lack of physical principles to guide learning from complex data, resulting in reduced prediction accuracy and interpretability when applied to infer cell population dynamics. RESULTS: Here, we propose PI-SDE, a physics-informed neural stochastic differential equation (SDE) framework that combines the Hamilton-Jacobi (HJ) equation and neural SDE to learn cellular dynamics. Grounded in potential energy theory of biological systems, PI-SDE integrates the principle of least action by enforcing the HJ equation when reconstructing cellular potential energy function. This approach not only facilitates accurate predictions, but also improves interpretability, especially in the reconstructed potential energy landscape. Through benchmarking on two real scRNA-seq datasets, we demonstrate the importance of incorporating the HJ regularization term in dynamic inference, especially in predicting gene expression at held-out time points. Meanwhile, the learned potential energy landscape provides biologically interpretable insights into the process of cell differentiation. Our framework enhances model performance, while maintaining robustness and stability. AVAILABILITY: PI-SDE software is available at https://github.com/QiJiang-QJ/PI-SDE.
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Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Redes Neurales de la Computación , Análisis de Secuencia de ARN/métodos , Humanos , RNA-Seq/métodos , Biología Computacional/métodos , Algoritmos , Análisis de Expresión Génica de una Sola CélulaRESUMEN
We report a novel visible-light-driven photoredox-catalyzed cascade reaction involving Conia-ene-type cyclization and Smiles rearrangement initiated from alkyne-tethered α-sulfonyl esters. This methodology not only facilitates the rapid synthesis of a broad spectrum of highly substituted methylenecarbocycles but also introduces a new mechanistic pathway with aryl group migration, surpassing the conventional 1,5-hydrogen shift typically observed in Conia-ene reactions.
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The incidence of tuberculosis (TB) has declined more slowly in rural than urban areas in China, and data on the patterns of transmission and the high-risk populations in rural areas remains scarce. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in rural Linzhou City, Henan Province from July 2018 to February 2023. Genomic clusters were defined based on whole-genome sequencing and risk factors for clustering were identified by logistic regression. Transmission events were inferred with phybreak and transmission links were sought through epidemiological investigation of clustered patients. Logistic regression was used to explore the relationship between genomic differences of patient isolates and geographical distances of patient residences. Spatial hotspots were defined using kernel density estimation. Of 455 culture-positive patients, 430 were included in the final analysis. Overall, 192 (44.7%,192/430) patients were grouped into 49 clusters. Clusters containing ≥5 patients accounted for 18.4% (9/49) of the clusters and clustering was highest in student patients. No super-spreaders were detected. Confirmed epidemiologic links were identified for only 18.2% of clustered patients. The clustering risk decreased rapidly with increasing distances between patient residences, but 77.6% of clustered patient pairs lived ≥5.0 km apart. Both the Central Subdistrict and Rencun Township were identified as hotspots for TB transmission. Recent transmission appears to be an important driver of the TB burden in Linzhou. The formulation of effective strategies to reduce TB incidence in rural areas will require further studies to identify high-risk populations and venues where local inhabitants congregate and transmit the infection.
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Mycobacterium tuberculosis , Población Rural , Humanos , China/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/clasificación , Estudios Prospectivos , Adulto Joven , Factores de Riesgo , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/transmisión , Tuberculosis Pulmonar/microbiología , Secuenciación Completa del Genoma , Incidencia , Anciano , Adolescente , Análisis por Conglomerados , Tuberculosis/epidemiología , Tuberculosis/transmisión , Tuberculosis/microbiologíaRESUMEN
OBJECTIVE: Nucleotide metabolic reprogramming as a hallmark of cancer is closely related to the occurrence and progression of cancer. We aimed to comprehensively analyze the nucleotide metabolism-related gene set and clinical significance in gliomas. METHODS: The RNA sequencing data of 702 gliomas from the Cancer Genome Atlas (TCGA) dataset were included as the training set, and the RNA sequencing data from the other three datasets (CGGA, GSE16011, and Rembrandt) were used as independent validation sets. Survival curve, Cox regression analysis, time-dependent ROC curve and nomogram model were performed to evaluate prognostic power of signature. R language was the main tool for bioinformatic analysis and graphical work. RESULTS: Based on the expression profiles of nucleotide metabolism-related genes, consensus clustering identified two robust clusters with different prognosis. We then developed a nucleotide metabolism-related signature that was closely related to clinical, pathological, and genomic characteristics of gliomas. And ROC curve showed that our signature was a potential biomarker for mesenchymal subtype. Survival curve and Cox regression analysis revealed signature as an independent prognostic factor for gliomas. In addition, we constructed a nomogram model to predict individual survival. Finally, functional analysis showed that nucleotide metabolism not only affected cell division and cell cycle, but also was associated with immune response in gliomas. CONCLUSION: We developed a nucleotide metabolism-related signature to predict prognosis and provided new insights into the role of nucleotide metabolism in gliomas.
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Imatinib-induced skin rash poses a significant challenge for patients with gastrointestinal stromal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. However, the underlying mechanism of imatinib-induced skin rashes in gastrointestinal stromal tumor patients remains unclear. A total of 51 patients (27 with rash and 24 without rash) were enrolled in our study. Blood samples were collected concomitantly with the onset of clinical manifestations of rashes, and simultaneously collecting clinical relevant information. The imatinib concentration and untargeted metabolomics were performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. There were no significant differences in age, gender, imatinib concentration and white blood cells count between the rash group and the control group. However, the rash group exhibited a higher eosinophil count (P<0.05) and lower lymphocyte count (P<0.05) compared to the control group. Untargeted metabolomics analysis found that 105 metabolites were significantly differentially abundant. The univariate analysis highlighted erucamide, linoleoylcarnitine, and valine betaine as potential predictive markers (AUC≥0.80). Further enriched pathway analysis revealed primary metabolic pathways, including sphingolipid signaling pathway, sphingolipid metabolism, cysteine and methionine metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, and biosynthesis of amino acids. These findings suggest that the selected differential metabolites could serve as a foundation for the prediction and management of imatinib-induced skin rash in gastrointestinal stromal tumor patients.
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Antineoplásicos , Exantema , Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Mesilato de Imatinib , Metabolómica , Humanos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Mesilato de Imatinib/efectos adversos , Mesilato de Imatinib/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Exantema/inducido químicamente , Neoplasias Gastrointestinales/tratamiento farmacológico , Anciano , AdultoRESUMEN
Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.
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Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Femenino , Preescolar , Lactante , Niño , Vasos Coronarios/patología , Vasos Coronarios/diagnóstico por imagen , Ecocardiografía , Coagulación Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/etiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológicoRESUMEN
Quantitative PCR (qPCR) is the gold standard for detection and quantitation of known DNA targets, but the scarcity of spectrally distinct fluorophores and filter sets limits the number of detectable targets. Here, we introduce color cycle multiplex amplification (CCMA) to significantly increase the number of detectable DNA targets in a single qPCR reaction using standard instrumentation. In CCMA, presence of one DNA target species results in a pre-programmed pattern of fluorescence increases. This pattern is distinguished by cycle thresholds (Cts) through rationally designed delays in amplification. For example, we design an assay wherein Staphylococcus aureus sequentially induces FAM, then Cy5.5, then ROX fluorescence increases with more than 3 cycles between each signal. CCMA offers notably higher potential for multiplexing because it uses fluorescence permutation rather than combination. With 4 distinct fluorescence colors, CCMA theoretically allows the detection of up to 136 distinct DNA target sequences using fluorescence permutation. Experimentally, we demonstrated a single-tube qPCR assay screening 21 sepsis-related bacterial DNA targets in samples of blood, sputum, pleural effusion and bronchoalveolar lavage fluid, with 89% clinical sensitivity and 100% clinical specificity, showing its potential as a powerful tool for advanced quantitative screening in molecular diagnostics.
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The efficiency and stability of perovskite module devices are mainly limited by the quality of scalable perovskite films and sub-cells' lateral contact. Here, firstly, we report constant low temperature substrate to regulate the growth of perovskite intermediate films to slow down the crystallization for obtaining high-quality homogeneous perovskite films in large scale size, which avoid the effect of the ambient temperature on the film quality. Secondly, a scribing step named P1.5 was added before the top function layers deposition, the diffusion barrier layer can be formed "naturally" at the interconnection interface without introducing any additional materials, which well alleviates the diffusion degradation process. As a result, our inverted perovskite devices exhibit a very small efficiency loss with area expansion comparable to other photovoltaic devices (for example, Cadmium Telluride), the perovskite module (aperture area 14.61 cm2) shows a certified quasi-steady-state power conversion efficiency of 22.73%, and the module maintaining over 90% of its initial efficiency after 1000 hours of continuous operation under illumination.
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Understanding the determinants of long-term liver metastasis (LM) outcomes in gastrointestinal stromal tumor (GIST) patients is crucial. We established the feature selection model of intratumoral microbiome at the surgery, achieving robust predictive accuracies of 0.953 and 0.897 AUCs in discovery (n = 74) and validation (n = 34) cohorts, respectively. Notably, despite the significant reduction in LM occurrence with adjuvant imatinib (AI) treatment, intratumoral microbiome exerted independently stronger effects on post-operative LM. Employing both 16S and full-length rRNA sequencing, we pinpoint intracellular Shewanella algae as a foremost LM risk factor in both AI- and non-AI-treated patients. Experimental validation confirmed S. algae's intratumoral presence in GIST, along with migration/invasion-promoting effects on GIST cells. Furthermore, S. algae promoted LM and impeded AI treatment in metastatic mouse models. Our findings advocate for incorporating intratumoral microbiome evaluation at surgery, and propose S. algae as a therapeutic target for LM suppression in GIST.
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Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Mesilato de Imatinib , Neoplasias Hepáticas , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/microbiología , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/microbiología , Animales , Ratones , Femenino , Masculino , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/microbiología , Quimioterapia Adyuvante/métodos , Persona de Mediana Edad , Microbiota/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , AncianoRESUMEN
Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1ß and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.
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OBJECTIVE: To investigate the application value of ultrasound technology in transurethral enucleation and resection of the prostate (TUERP). METHODS: This study included 78 BPH patients admitted in our hospital from June 2021 to June 2023, aged 70.68±8.63 years and with the indication of surgery. We randomly divided them into two groups to receive TUERP (the control group, n = 39) and ultrasound-assisted TUERP (the US-TUERP group, n = 39). We statistically analyzed and compared the relevant parameters obtained before and after operation between the two groups. RESULTS: No statistically significant differences were observed in the operation time and bladder irrigation time between the two groups (P > 0.05). More glandular tissues were removed but less intraoperative bleeding and fewer perioperative complications occurred in the US-TUERP group than in the control. Compared with the baseline, IPSS, postvoid residual urine volume (PVR), quality of life score (QOL) and maximum urinary flow rate (Qmax) were significantly improved in both groups at 1 and 3 months after surgery, even more significantly in the US-TUERP than in the control group (P < 0.05). CONCLUSION: US-TUERP helps achieve complete resection of the hyperplastic prostatic tissue along the surgical capsule at the anatomical level, with a higher safety, fewer perioperative complications, and better therapeutic effects.
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Próstata , Hiperplasia Prostática , Resección Transuretral de la Próstata , Ultrasonografía , Humanos , Masculino , Resección Transuretral de la Próstata/métodos , Anciano , Hiperplasia Prostática/cirugía , Próstata/cirugía , Calidad de Vida , Resultado del Tratamiento , Tempo OperativoRESUMEN
High-quality panoramic images with a Field of View (FoV) of 360° are essential for contemporary panoramic computer vision tasks. However, conventional imaging systems come with sophisticated lens designs and heavy optical components. This disqualifies their usage in many mobile and wearable applications where thin and portable, minimalist imaging systems are desired. In this paper, we propose a Panoramic Computational Imaging Engine (PCIE) to achieve minimalist and high-quality panoramic imaging. With less than three spherical lenses, a Minimalist Panoramic Imaging Prototype (MPIP) is constructed based on the design of the Panoramic Annular Lens (PAL), but with low-quality imaging results due to aberrations and small image plane size. We propose two pipelines, i.e. Aberration Correction (AC) and Super-Resolution and Aberration Correction (SR&AC), to solve the image quality problems of MPIP, with imaging sensors of small and large pixel size, respectively. To leverage the prior information of the optical system, we propose a Point Spread Function (PSF) representation method to produce a PSF map as an additional modality. A PSF-aware Aberration-image Recovery Transformer (PART) is designed as a universal network for the two pipelines, in which the self-attention calculation and feature extraction are guided by the PSF map. We train PART on synthetic image pairs from simulation and put forward the PALHQ dataset to fill the gap of real-world high-quality PAL images for low-level vision. A comprehensive variety of experiments on synthetic and real-world benchmarks demonstrates the impressive imaging results of PCIE and the effectiveness of the PSF representation. We further deliver heuristic experimental findings for minimalist and high-quality panoramic imaging, in terms of the choices of prototype and pipeline, network architecture, training strategies, and dataset construction. Our dataset and code will be available at https://github.com/zju-jiangqi/PCIE-PART.
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An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 µM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 µM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 µM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.
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Antivirales , Diseño de Fármacos , Flavonoles , SARS-CoV-2 , Antivirales/farmacología , Antivirales/síntesis química , Antivirales/química , Chlorocebus aethiops , SARS-CoV-2/efectos de los fármacos , Células Vero , Flavonoles/farmacología , Flavonoles/síntesis química , Flavonoles/química , Animales , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Replicación Viral/efectos de los fármacos , Estructura Molecular , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , HumanosRESUMEN
BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.
Asunto(s)
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Inhibidores de la Bomba de Protones , Pirroles , Sulfonamidas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/diagnóstico , Persona de Mediana Edad , Masculino , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Femenino , Estudios Prospectivos , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , China/epidemiología , Quimioterapia Combinada/métodos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Resultado del Tratamiento , Adulto , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Antibacterianos/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Anciano , Pueblos del Este de AsiaRESUMEN
BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.