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1.
Food Res Int ; 192: 114852, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39147529

RESUMEN

Crohn's disease (CD) is a chronic and progressive inflammatory disease that can involve any part of the gastrointestinal tract. The protective role of dietary polyphenols has been documented in preclinical models of CD. Gut microbiota mediates the metabolism of polyphenols and affects their bioactivity and physiological functions. However, it remains elusive the capacity of microbial polyphenol metabolism in CD patients and healthy controls (HCs) along with its correlation with polyphenols intake and polyphenol-derived metabolites. Thus, we aimed to decode polyphenol metabolism in CD patients through aspects of diet, gut microbiota, and metabolites. Dietary intake analysis revealed that CD patients exhibited decreased intake of polyphenols. Using metagenomic data from two independent clinical cohorts (FAH-SYSU and PRISM), we quantified abundance of polyphenol degradation associated bacteria and functional genes in CD and HCs and observed a lower capacity of flavonoids degradation in gut microbiota residing in CD patients. Furthermore, through analysis of serum metabolites and enterotypes in participants of FAH-SYSU cohort, we observed that CD patients exhibited reduced levels of serum hippuric acid (HA), one of polyphenol-derived metabolites. HA level was higher in healthier enterotypes (characterized by dominance of Ruminococcaceae and Prevotellaceae, dominant by HCs) and positively correlated with multiple polyphenols intake and abundance of bacteria engaged in flavonoids degradation as well as short-chain fatty acid production, which could serve as a biomarker for effective polyphenol metabolism by the gut microbiota and a healthier gut microbial community structure. Overall, our findings provide a foundation for future work exploring the polyphenol-based or microbiota-targeted therapeutic strategies in CD.


Asunto(s)
Enfermedad de Crohn , Dieta , Microbioma Gastrointestinal , Polifenoles , Humanos , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/tratamiento farmacológico , Microbioma Gastrointestinal/fisiología , Polifenoles/metabolismo , Femenino , Masculino , Adulto , Hipuratos/metabolismo , Persona de Mediana Edad , Adulto Joven , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Heces/microbiología
2.
Microbiome ; 12(1): 152, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152482

RESUMEN

BACKGROUND: H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. RESULTS: Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. CONCLUSIONS: Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.


Asunto(s)
Enfermedad de Crohn , Microbioma Gastrointestinal , Sulfuro de Hidrógeno , Sulfatos , Enfermedad de Crohn/microbiología , Humanos , Sulfuro de Hidrógeno/metabolismo , Animales , Ratones , Sulfatos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Heces/microbiología , Disbiosis/microbiología , Colon/microbiología , Metagenómica , Oxidación-Reducción , Modelos Animales de Enfermedad , Femenino
3.
BMC Health Serv Res ; 24(1): 887, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097710

RESUMEN

BACKGROUND: The Diagnosis-Intervention Packet (DIP) payment system, initiated by China's National Healthcare Security Administration, is designed to enhance healthcare efficiency and manage rising healthcare costs. This study aims to evaluate the impact of the DIP payment reform on inpatient care in a specialized obstetrics and gynecology hospital, with a focus on its implications for various patient groups. METHODS: To assess the DIP policy's effects, we employed the Difference-in-Differences (DID) approach. This method was used to analyze changes in total hospital costs and Length of Stay (LOS) across different patient groups, particularly within select DIP categories. The study involved a comprehensive examination of the DIP policy's influence pre- and post-implementation. RESULTS: Our findings indicate that the implementation of the DIP policy led to a significant increase in both total costs and LOS for the insured group relative to the self-paying group. The study further identified variations within DIP groups both before and after the reform. In-depth analysis of specific disease groups revealed that the insured group experienced notably higher total costs and LOS compared to the self-paying group. CONCLUSIONS: The DIP reform has led to several challenges, including upcoding and diagnostic ambiguity, because of the pursuit of higher reimbursements. These findings underscore the necessity for continuous improvement of the DIP payment system to effectively tackle these challenges and optimize healthcare delivery and cost management.


Asunto(s)
Reforma de la Atención de Salud , Tiempo de Internación , Humanos , Reforma de la Atención de Salud/economía , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/economía , China , Femenino , Costos de Hospital/estadística & datos numéricos , Mecanismo de Reembolso , Pacientes Internos/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Adulto
4.
BMJ Open ; 14(8): e085731, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134432

RESUMEN

INTRODUCTION: Asian American caregivers supporting loved ones with dementia experience greater burden and more stress than other racial/ethnic groups, warranting the need for more culturally and linguistically appropriate formal support, such as in nursing homes. Transitioning loved ones into nursing homes with dementia care units is a complex process that can be impacted by a multitude of factors. Employing several established frameworks, including the socioecological model, this qualitative study will focus on the largest Asian American subgroup (people of Chinese descent) and explore the experience of family caregivers as they support the transition of their loved ones with dementia into nursing homes in the USA. Our focus will be on the nuanced influences of the Chinese language and culture and COVID-19-related social isolation and racial discrimination. METHODS AND ANALYSIS: Recruitment will take place starting in January 2024. Current or former Chinese caregivers for Chinese loved ones with dementia, able to communicate in Mandarin Chinese or English, and currently residing in the USA will be eligible. Key informants with intimate understanding and experience with this population will also be included. Data will be collected through 2024 using semistructured, in-depth interviews with each participant. Depending on participants' preferences, interviews will be conducted in either Mandarin Chinese or English and either in person, via Zoom or by phone. Interviews will be transcribed verbatim. Iterative thematic analysis will be employed. A coding structure will be developed based on interview questions and themes and patterns that are revealed through data immersion. Transcripts, prepared in their original language, will be dual-coded by bilingual researchers using NVivo 14. Consensus summaries of themes will be prepared. Relevant direct quotes for each thematic area will be identified (those in Chinese will be translated into English) and cited in reports and manuscripts. ETHICS AND DISSEMINATION: The study is approved by the UMass Chan Medical School Institutional Review Board (ID: STUDY00001376). Findings will be published in peer-review journals following the consolidated criteria for reporting qualitative research.


Asunto(s)
Asiático , Cuidadores , Demencia , Casas de Salud , Investigación Cualitativa , Humanos , Cuidadores/psicología , Demencia/etnología , Demencia/enfermería , Asiático/psicología , China/etnología , COVID-19/etnología , Estados Unidos , SARS-CoV-2 , Familia/psicología , Aislamiento Social/psicología , Pueblos del Este de Asia
5.
J Med Chem ; 67(14): 12439-12458, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38996004

RESUMEN

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.


Asunto(s)
Aldehídos , Fármacos Antiobesidad , Hidrazonas , Obesidad , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/síntesis química , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/química , Hidrazonas/farmacología , Hidrazonas/química , Hidrazonas/síntesis química , Hidrazonas/farmacocinética , Hidrazonas/uso terapéutico , Ratones , Relación Estructura-Actividad , Aldehídos/química , Masculino , Obesidad/tratamiento farmacológico , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones Obesos , Estructura Molecular
6.
Nat Prod Res ; : 1-6, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980006

RESUMEN

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

7.
World J Clin Cases ; 12(20): 4247-4255, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39015909

RESUMEN

BACKGROUND: Colorectal cancer is the second leading cause of cancer-related deaths among digestive tract malignancies, following gastric cancer. Sleep is of great significance for maintaining human health. The incidence of sleep disorders in patients with cancer is approximately twice that observed in the general population. Lack of sleep can prolong hospital stays, increase the likelihood of infection, and increase mortality rates. Therefore, studying the factors related to sleep quality is significant for improving the quality of life of patients with malignant tumors of the digestive tract. AIM: To investigate the relationships among sleep quality, disease uncertainty, and psychological resilience in patients undergoing chemotherapy for digestive tract malignancies. METHODS: A total of 131 patients with malignant digestive tract tumors who were treated at Hefei BOE Hospital between April 2021 and September 2022 were selected as research participants. Based on their Pittsburgh Sleep Quality Index (PSQI) scores, participants were divided into either the sleep disorder group (PSQI score > 7) or the normal sleep group (PSQI score ≤ 7). The clinical data-together with the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and Connor-Davidson Resilience Scale (CD-RISC) scores-were compared. RESULTS: In this study, 78 (59.54%) patients with digestive tract malignancies developed sleep disorders after chemotherapy. Sleep disorder incidence was higher in patients with colorectal cancer than in those with gastric and esophageal cancers (P < 0.05). The total MUIS-A score and those for each item in the sleep disorder group were higher than those in the normal sleep group. The total CD-RISC score and those for each item in the sleep disorder group were lower than those in the normal sleep group (P < 0.05). The PSQI scores of patients with malignant digestive tract tumors were positively correlated with the scores for lack of disease information, disease uncertainty, and unpredictability in the MUIS-A and negatively correlated with the scores for tenacity, self-improvement, and optimism in the CD-RISC (P < 0.05). CONCLUSION: Patients undergoing chemotherapy for digestive tract malignancies are prone to sleep problems related to disease uncertainty and psychological resilience. Therefore, interventions can be implemented to improve their sleep quality.

8.
Genome Biol ; 25(1): 179, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38972974

RESUMEN

Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer's disease model, we demonstrate silencing of mutant APPswe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.


Asunto(s)
Enfermedad de Alzheimer , Silenciador del Gen , ARN Mensajero , ARN Mensajero/genética , ARN Mensajero/metabolismo , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Animales , Ratones , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , División del ARN , Vectores Genéticos , Dependovirus/genética
9.
World J Clin Cases ; 12(19): 3866-3872, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38994274

RESUMEN

BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.

10.
Int J Oncol ; 65(2)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38873993

RESUMEN

Genes encoding subunits of SWI/SNF (BAF) chromatin­remodeling complexes are recurrently mutated in a broad array of tumor types, and among the subunits, ARID1A is the most frequent target with mutations. In the present study, it was reported that ARID1A inhibits the epithelial­mesenchymal transition (EMT) and stemness of ovarian cancer cells, accompanied by reduced cell viability, migration and colony formation, suggesting that ARID1A acts as a tumor suppressor in ovarian cancer. Mechanistically, ARID1A exerts its inhibitory effects on ovarian cancer cells by activating the Hippo signaling pathway. Conversely, the overexpression of a gain­of­function transcriptional co­activator with PDZ­binding motif (TAZ) mutant (TAZ­Ser89) effectively reverses the effects induced by ARID1A. In addition, activation of Hippo signaling apparently upregulates ARID1A protein expression, whereas ectopic expression of TAZ­Ser89 results in the markedly decreased ARID1A levels, indicating a feedback of ARID1A­TAZ in regulating ovarian cancer cell EMT and stemness. Thus, the present study uncovered the role of ARID1A through the Hippo/TAZ pathway in modulating EMT and stemness of ovarian cancer cells, and providing with evidence that TAZ inhibitors could effectively prevent initiation and metastasis of ovarian cancer cases where ARID1A is lost or mutated.


Asunto(s)
Proteínas de Unión al ADN , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo , Células Madre Neoplásicas , Neoplasias Ováricas , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Factores de Transcripción , Humanos , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Línea Celular Tumoral , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Movimiento Celular , Proliferación Celular , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética
11.
Phytochemistry ; 225: 114193, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38908463

RESUMEN

Lathyrisone A (1), a diterpene with an undescribed tricyclic 6/6/6 fused carbon skeleton, along with spirolathyrisins B-D (3-5), three diterpenes with a rare [4.5.0] spirocyclic carbon skeleton, and one known compound (2) were isolated from the roots of Euphorbia lathyris. Their chemical structures were characterized by extensive spectroscopic analysis, X-ray crystallography, ECD and quantum chemistry calculation. A plausible biosynthetic pathway for compounds 1-5 was proposed, which suggested it is a competitive pathway for ingenol biosynthesis in the plant. The anti-fungal activities of these compounds were tested, especially, compound 2 showed stronger anti-fungal activities against Fusarium oxysporum and Alternaria alternata than the positive control fungicide thiophanate-methyl. The preliminary structure-activity relationship of compounds 1-5 was also discussed. These results not only expanded the chemical diversities of E. lathyris, but also provided a lead compound for the control of plant pathogens.


Asunto(s)
Alternaria , Antifúngicos , Diterpenos , Euphorbia , Fusarium , Pruebas de Sensibilidad Microbiana , Raíces de Plantas , Euphorbia/química , Diterpenos/química , Diterpenos/farmacología , Diterpenos/aislamiento & purificación , Raíces de Plantas/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Relación Estructura-Actividad , Fusarium/efectos de los fármacos , Alternaria/efectos de los fármacos , Estructura Molecular , Descubrimiento de Drogas , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga
12.
Genomics ; 116(4): 110876, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849019

RESUMEN

Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , Masculino , Persona de Mediana Edad , Femenino , Detección Precoz del Cáncer/métodos , Anciano , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Aprendizaje Automático , Adulto , Secuenciación Completa del Genoma/métodos , Fragmentación del ADN
13.
Immunotargets Ther ; 13: 273-286, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881648

RESUMEN

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

14.
Entropy (Basel) ; 26(6)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38920537

RESUMEN

Coreference resolution is a key task in Natural Language Processing. It is difficult to evaluate the similarity of long-span texts, which makes text-level encoding somewhat challenging. This paper first compares the impact of commonly used methods to improve the global information collection ability of the model on the BERT encoding performance. Based on this, a multi-scale context information module is designed to improve the applicability of the BERT encoding model under different text spans. In addition, improving linear separability through dimension expansion. Finally, cross-entropy loss is used as the loss function. After adding BERT and span BERT to the module designed in this article, F1 increased by 0.5% and 0.2%, respectively.

15.
Environ Int ; 190: 108841, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38917626

RESUMEN

OBJECTIVES: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM2.5 and PM1 (PM with an aerodynamic equivalent diameter <2.5 µm and <1 µm, respectively) with sleep disorders in children. METHODS: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM2.5 and PM1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments. RESULTS: Long-term PM2.5 and PM1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM2.5 and PM1 per 10 µg/m3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM1 were found than that of PM2.5 in southeast region. CONCLUSION: Long-term PM2.5 and PM1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region.

16.
Future Sci OA ; 10(1): FSO906, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827794

RESUMEN

The feasibility of surgery after immunotherapy for mediastinal liposarcoma remains uncertain. Besides, the case of immunotherapy for liposarcoma is still lacking. We report a case of recurrence after resection of a left mediastinal liposarcoma. After recurrence, one course of pembrolizumab plus anlotinib hydrochloride showed no tumor shrinkage, and genetic testing showed CDK4 amplification and PD-L1 TPS <1%; therefore, the plan was changed to one course of pembrolizumab plus palbociclib, but the tumor still did not shrink. Thus, second tumor resection was performed. In addition, the postoperative pathology was still well-differentiated liposarcoma. The significance of immunotherapy in liposarcoma still needs to be further explored. In the absence of surgical contraindications, secondary surgery might be feasible.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38904613

RESUMEN

Objective: To analyze the efficacy and safety of bevacizumab combined with chemotherapy in the treatment of malignant pleural effusion of lung cancer. Methods: Lung cancer patients with malignant pleural effusion (n = 60 cases) treated in our hospital from January 2020 to December 2022 were retrospectively analyzed. They were divided into a control group (patients receiving conventional chemotherapy) and an observation group (patients receiving bevacizumab combined with chemotherapy). The two groups were age and sex-matched. The therapeutic effects, adverse reactions, quality of life (physiological status, social and family status, emotional status, and functional status), levels of serum tumor markers (cytokeratin 19 fragment, tumor-specific growth factor, and carcinoembryonic antigen), pain degree of the two groups before and after treatment, and the psychological states before and after treatment (anxiety and depression scores) of the two groups were compared. Results: The results obtained shows that the observation group has improved treatment outcome than the control group, P < .05. Similarly, the observation group reported higher physiological status, social and family status, emotional status, functional status and other quality of life compared to the control group, P < .05. Interestingly, the observation group showed lower levels of serum tumor markers than the control group, P < .05. Upon comparison of the pain degree of the two groups after treatment, the observation group reported a lesser degree of pain than the control group, P < .05. Although no significant difference was observed in the depression and anxiety scores of the two groups prior to the treatment, the observation group displayed improved psychological state compared to the control group, P < .05. Conclusion: Bevacizumab combined with chemotherapy has outstanding curative effect on malignant pleural effusion of lung cancer.

18.
Front Med ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907157

RESUMEN

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N6,2'-O-dimethyladenosine (m6Am), N4-acetylcytidine (ac4C), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc. A novel perspective indicates that regulatory subunits and post-translational modifications (PTMs) are involved in the regulation of writer, eraser, and reader functions in mediating RNA modifications, tumorigenesis, and anticancer therapy. In this review, we summarize the advances made in the knowledge of different RNA modifications (especially m6A) and focus on RNA modification regulators with functions modulated by a series of factors in cancer, including regulatory subunits (proteins, noncoding RNA or peptides encoded by long noncoding RNA) and PTMs (acetylation, SUMOylation, lactylation, phosphorylation, etc.). We also delineate the relationship between RNA modification regulator functions and carcinogenesis or cancer progression. Additionally, inhibitors that target RNA modification regulators for anticancer therapy and their synergistic effect combined with immunotherapy or chemotherapy are discussed.

19.
United European Gastroenterol J ; 12(6): 772-779, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38753528

RESUMEN

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.


Asunto(s)
Detección Precoz del Cáncer , Gastroscopía , Aumento de la Imagen , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Gastroscopía/métodos , Detección Precoz del Cáncer/métodos , Anciano , Aumento de la Imagen/métodos , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/patología , Gastritis Atrófica/diagnóstico por imagen , Adulto
20.
Eur J Histochem ; 68(2)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38742403

RESUMEN

Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.


Asunto(s)
Emodina , Fibrosis , Mitocondrias , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Insuficiencia Renal Crónica , Animales , Emodina/farmacología , Emodina/uso terapéutico , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Fibrosis/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Homeostasis/efectos de los fármacos , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Obstrucción Ureteral/patología , Obstrucción Ureteral/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/metabolismo , Línea Celular
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