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1.
J Hazard Mater ; 476: 135150, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986416

RESUMEN

Antibiotic selective pressure in aquaculture systems often results in the antibiotic resistance genes (ARGs) proliferation. Nonetheless, a paucity of data exists concerning the mechanisms of ARGs development in aquaculture systems without the influences of antibiotics. This study utilized metagenomic approaches to elucidate the dynamics and transfer mechanisms of ARGs throughout the aquaculture of Pacific white shrimp. A marked change in the resistome was observed throughout the aquaculture without antibiotics. The total ARGs relative abundance increased from 0.05 to 0.33 by day 90 of cultivation, with even higher in mixed wastewater (0.44). Both bacterial communities and mobile genetic elements play pivotal roles in the development of ARGs. Metagenome-assembled genomes showed enrichment of environmentally intrinsic ARGs on chromosomes including macB and mdtK. The plasmid-mediated horizontal transfer was recognized as a principal factor contributing to the rise of ARGs, particularly for tetG and floR, and this led to an escalation of resistance risk, peaking at a risks core of 35.43 on day 90. This study demonstrates that horizontal gene transfer plays a crucial role in ARGs development without antibiotic pressure, which can provide a theoretical foundation for controlling ARGs proliferation in aquaculture systems.

2.
Angew Chem Int Ed Engl ; : e202411166, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008335

RESUMEN

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

3.
Ren Fail ; 46(2): 2367708, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38973391

RESUMEN

BACKGROUND: Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored. AIMS: To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3. METHODS: Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated ß-galactosidase (SA-ß-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification. RESULTS: The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process. CONCLUSIONS: Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.


Asunto(s)
Senescencia Celular , Lipopolisacáridos , Macrófagos , Proteínas de la Membrana , Músculo Liso Vascular , Proteínas de Unión al ARN , Calcificación Vascular , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Lipopolisacáridos/farmacología , Calcificación Vascular/patología , Calcificación Vascular/metabolismo , Macrófagos/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de Unión al ARN/metabolismo , Humanos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Células Cultivadas , Animales , Osteogénesis , Transdiferenciación Celular
4.
World J Gastrointest Surg ; 16(6): 1681-1690, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38983336

RESUMEN

BACKGROUND: The Da Vinci robot-assisted surgery technique has been widely used in laparoscopic mesangectomy for rectal cancer. However, the short-term efficacy of these procedures compared to traditional laparoscopic surgery remains controversial. The purpose of this study was to compare and analyze the short- and medium-term efficacy of Da Vinci robot and laparoscopic surgery in total mesangectomy (TME) for rectal cancer, so as to provide guidance and reference for clinical practice. AIM: To investigate the safety and long-term efficacy of robotic and laparoscopic total mesorectal resection for the treatment of rectal cancer. METHODS: The clinicopathologic data of 240 patients who underwent TME for rectal cancer in the Anorectal Department of People's Hospital of Xinjiang Uygur Autonomous Region from August 2018 to March 2023 were retrospectively analyzed. Among them, 112 patients underwent laparoscopic TME (L-TME) group, and 128 patients underwent robotic TME (R-TME) group. The intraoperative, postoperative, and follow-up conditions of the two groups were compared. RESULTS: The conversion rate of the L-TME group was greater than that of the R-TME group (5.4% vs 0.8%, χ 2 = 4.417, P = 0.036). The complication rate of the L-TME group was greater than that of the R-TME group (32.1% vs 17.2%, χ 2 = 7.290, P = 0.007). The percentage of positive annular margins in the L-TME group was greater than that in the R-TME group (7.1% vs 1.6%, χ 2 = 4.658, P = 0.031). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate of the L-TME group were lower than those of the R-TME group (74.1% vs 85.2%, χ 2 = 4.962, P = 0.026; 81.3% vs 91.4%, χ 2 = 5.494, P = 0.019); in patients with American Joint Committee on Cancer stage III DFS rate and OS rate in the L-TME group were significantly lower than those in the R-TME group (52.5% vs 76.1%, χ 2 = 5.799, P = 0.016; 65.0% vs 84.8%, χ 2 = 4.787, P = 0.029). CONCLUSION: Compared with the L-TME group, the R-TME group had a better tumor prognosis and was more favorable for patients with rectal cancer, especially for patients with stage III rectal cancer.

5.
Inorg Chem ; 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38973091

RESUMEN

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H2) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co-Salen-P and Fe-Salen-P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H2 evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H2 generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H2 generation rate of Co-Salen-P reaches as high as 542.5 µmol g-1 h-1, which is not only 6 times higher than that of Fe-Salen-P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co-Salen-P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H2 production.

6.
FEBS J ; 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38973142

RESUMEN

Accumulating evidence shows that inflammation is essential for embryo implantation and decidualization. Histamine, a proinflammatory factor that is present in almost all mammalian tissues, is synthesized through decarboxylating histidine by histidine decarboxylase (HDC). Although histamine is known to be essential for decidualization, the underlying mechanism remains undefined. In the present study, histamine had no obvious direct effects on in vitro decidualization in mice. However, the obvious differences in HDC protein levels between day 4 of pregnancy and day 4 of pseudopregnancy, as well as between delayed and activated implantation, suggested that the blastocyst may be involved in regulating HDC expression. Furthermore, blastocyst-derived tumor necrosis factor α (TNFα) significantly increased HDC levels in the luminal epithelium. Histamine increased the levels of amphiregulin (AREG) and disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) proteins, which was abrogated by treatment with famotidine, a specific histamine type 2 receptor (H2R) inhibitor, or by TPAI-1 (a specific inhibitor of ADAM17). Intraluminal injection of urocanic acid (HDC inhibitor) on day 4 of pregnancy significantly reduced the number of implantation sites on day 5 of pregnancy. TNFα-stimulated increases in HDC, AREG and ADAM17 protein levels was abrogated by urocanic acid, a specific inhibitor of HDC. Additionally, AREG treatment significantly promoted in vitro decidualization. Collectively, our data suggests that blastocyst-derived TNFα induces luminal epithelial histamine secretion, and histamine increases mouse decidualization through ADAM17-mediated AREG release.

7.
Cerebrovasc Dis ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38964301

RESUMEN

INTRODUCTION: There has been an increasing demand for imaging methods that provide a comprehensive evaluation of intracranial clot and collateral circulation, which are helpful for clinical decision-making and predicting functional outcomes. We aimed to quantitatively evaluate acute intracranial clot burden and collaterals on high-resolution magnetic resonance imaging (HR-MRI). METHODS: We analyzed acute ischemic stroke patients with internal carotid artery or middle cerebral artery occlusion in a prospective multicenter study. The clot burden was scored on a scale of 0-10 based on the clot location on HR-MRI. The collateral score was assigned on a scale of 0-3 using the minimum intensity projection from HR-MRI. Uni- and multivariable logistic regression analyses were performed to assess their correlation with clinical outcome (modified Rankin Scale >2 at 90 days). Thresholds were defined to dichotomize into low and high score groups and predictive performances were assessed for clinical and radiologic outcomes. RESULTS: Ninety-nine patients (mean age of 60.77 ± 11.54 years) were included in the analysis. The interobserver correlation was 0.89 (95% CI: 0.77-0.95) for the clot burden score and 0.78 (95% CI: 0.53-0.90) for the collateral score. Multivariable logistic regression analysis demonstrated that the collateral score (odds ratio: 0.41, 95% CI: 0.19-0.90) was significantly associated with clinical outcomes. A better functional outcome was observed in the group with clot burden scores greater than 7 (p=0.011). A smaller final infarct size and a higher diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score were observed in the group with collateral scores greater than 1 (all p<0.05). CONCLUSIONS: HR-MRI offers a new tool for quantitative assessment of clot burden and collaterals simultaneously in future clinical practices and research endeavors.

9.
Acta Pharmacol Sin ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862816

RESUMEN

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca2+ influx evoked by high K+ solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.

10.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 592-598, 2024 Jun 15.
Artículo en Chino | MEDLINE | ID: mdl-38926375

RESUMEN

OBJECTIVES: To investigate the value of single-phase gonadotropin releasing hormone (GnRH) stimulation test in the diagnosis of central precocious puberty (CPP) in girls with different levels of body mass index (BMI). METHODS: A retrospective analysis was performed for the data of 760 girls with breast development before 7.5 years of age who attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2023. According to the results of GnRH stimulation test and clinical manifestations, they were divided into a CPP group (297 girls) and a non-CPP group (463 girls). According to the values of BMI, the girls were divided into a normal weight group (540 girls), an overweight group (116 girls), and an obese group (104 girls). The receiver operating characteristic (ROC) curve was used to investigate the value of single-phase GnRH stimulation test in the diagnosis of CPP in girls with different levels of BMI. RESULTS: Luteinizing hormone (LH)/follicle-stimulating hormone at 30 minutes after GnRH stimulation had an area under the curve (AUC) of 0.985 in the diagnosis of CPP, which was higher than the AUC at 0, 60, and 90 minutes (P<0.05). LH at 30 minutes had a similar diagnostic value to LH at 60 minutes (P>0.05). LH at 30 minutes was negatively correlated with BMI and BMI-Z value (P<0.05).The AUC for diagnosing CPP in normal weight, overweight, and obese girls at 30 minutes LH was 0.952, 0.965, and 0.954, respectively (P<0.05). CONCLUSIONS: The 30-minute GnRH stimulation test has a good value in the diagnosis of CPP in girls with different levels of BMI and is expected to replace the traditional GnRH stimulation test, but the influence of BMI on LH level should be taken seriously.


Asunto(s)
Índice de Masa Corporal , Hormona Liberadora de Gonadotropina , Hormona Luteinizante , Pubertad Precoz , Humanos , Pubertad Precoz/diagnóstico , Pubertad Precoz/sangre , Femenino , Hormona Liberadora de Gonadotropina/sangre , Niño , Estudios Retrospectivos , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Curva ROC , Preescolar
11.
Front Cell Dev Biol ; 12: 1376414, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933332

RESUMEN

Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life quality of patients. Conventional uterine tissue transplantation-based models have been broadly used to investigate the pathogenic mechanism(s) of EM. Transgenic mice with whole body or uterine/pelvic tissue-specific labelling by the expression of GFP, ß-gal or other light-emitting or chromogenic markers enable investigators to analyze the contribution to endometriotic lesions by the donor or recipient side after uterine tissue transplantation. Moreover, when coupled to uterine tissue transplantation, transgenic mice with a specific EM-related gene knocked out or overexpressed make it possible to determine the gene's in vivo role(s) for EM pathogenesis. Furthermore, observations on the rise of de novo endometriotic lesions as well as structural/functional changes in the eutopic endometrium or pelvic tissues after gene manipulation will directly relate the cognate gene to the onset of EM. A major advantage of transgenic EM models is their efficiency for analyzing gene interactions with hormonal, dietetic and/or environmental factors. This review summarizes the features/sources/backgrounds of transgenic mice and their applications to EM studies concerning hormonal regulation, angiogenesis and inflammation. Findings from these studies, the advantages/disadvantages of transgenic EM models, and future expectations are also discussed.

12.
Poult Sci ; 103(8): 103881, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38865766

RESUMEN

Infectious bronchitis virus (IBV) is one of the most widely spread RNA viruses, causing respiratory, renal, and intestinal damage, as well as decreased reproductive performance in hens, leading to significant economic losses in the poultry industry. In this study, a new IBV strain designated as CK/CH/GX/LA/071423 was successfully isolated from the 60-day-old Three-Yellow chicken vaccinated with H120 and QXL87 vaccines. The complete genome sequence analysis revealed that the CK/CH/GX/LA/071423 strain shared a high similarity of 96.7% with the YX10 strain belonging to the GI-19 genotype. Genetic evolution analysis based on the IBV S1 gene showed that the CK/CH/GX/LA/071423 isolate belonged to the GI-19 genotype. Recombination analysis of the virus genome using RDP and Simplot software indicated that CK/CH/GX/LA/071423 was derived from recombination events between the YX10 and 4/91 vaccine strains, which was supported by phylogenetic analysis using gene sequences from the 3 regions. Furthermore, the S1 protein tertiary structure differences were observed between the CK/CH/GX/LA/071423 and the QXL87 and H120 vaccine strains. Pathogenicity studies revealed that the CK/CH/GX/LA/071423 caused death and led to pale and enlarged kidneys with abundant urate deposits, indicative of a nephropathogenic IBV strain. High virus titers were detected in the trachea, kidneys, and cecal tonsils, demonstrating broad tissue tropism. Throughout the experimental period, the virus positive rate in throat swabs of the infected group reached to 100%. These findings highlight the continued predominance of the QX genotype IBV in Guangxi of China and the ongoing evolution of different genotypes through genetic recombination, raising concerns about the efficacy of current IBV vaccines in providing effective protection to poultry.

14.
Nat Commun ; 15(1): 5081, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38876991

RESUMEN

Stomatal movement is vital for plants to exchange gases and adaption to terrestrial habitats, which is regulated by environmental and phytohormonal signals. Here, we demonstrate that hydrogen peroxide (H2O2) is required for light-induced stomatal opening. H2O2 accumulates specifically in guard cells even when plants are under unstressed conditions. Reducing H2O2 content through chemical treatments or genetic manipulations results in impaired stomatal opening in response to light. This phenomenon is observed across different plant species, including lycopodium, fern, and monocotyledonous wheat. Additionally, we show that H2O2 induces the nuclear localization of KIN10 protein, the catalytic subunit of plant energy sensor SnRK1. The nuclear-localized KIN10 interacts with and phosphorylates the bZIP transcription factor bZIP30, leading to the formation of a heterodimer between bZIP30 and BRASSINAZOLE-RESISTANT1 (BZR1), the master regulator of brassinosteroid signaling. This heterodimer complex activates the expression of amylase, which enables guard cell starch degradation and promotes stomatal opening. Overall, these findings suggest that H2O2 plays a critical role in light-induced stomatal opening across different plant species.


Asunto(s)
Peróxido de Hidrógeno , Luz , Estomas de Plantas , Estomas de Plantas/efectos de la radiación , Estomas de Plantas/metabolismo , Estomas de Plantas/fisiología , Peróxido de Hidrógeno/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiología , Arabidopsis/efectos de la radiación , Triticum/genética , Triticum/metabolismo , Triticum/fisiología , Triticum/efectos de la radiación , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Transducción de Señal , Fosforilación , Helechos/metabolismo , Helechos/efectos de la radiación , Helechos/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética
15.
Acta Pharmacol Sin ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834683

RESUMEN

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

16.
Front Public Health ; 12: 1392581, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38864017

RESUMEN

Purpose: Peak Expiratory Flow (PEF) is associated with a variety of adverse health outcomes in older adults; however, the relationship between PEF and frailty remains uncertain, and this study investigated the relationship between PEF and frailty within an olderly Asian demographic. Methods: Data were sourced from the Chinese Health and Retirement Longitudinal Study (CHARLS). Individuals in the study, all 60 years or older, underwent baseline PEF assessments quantified as standardized residual (SR) percentile values. The evaluation of frailty was conducted based on the criteria established by Fried. Participants without frailty at the outset were tracked over a four-year period, during which the relationships between PEF and frailty were examined through logistic regression and discrete-time Cox regression analyses. Results: Among 5,060 participants, cross-sectional analysis revealed that the prevalence of frailty was 2-3 times higher in the lower 10-49th and < 10th SR percentile groups compared to the 80-100th SR percentile group. The longitudinal study corroborated these results, showing an adjusted hazard ratio (HR) of 2.01 (95% CI, 1.15-3.51) for PEF SR percentiles below the 10th, in contrast to those between the 80th and 100th percentiles. Conclusion: PEF independently predicts and determines frailty in older adults. Declines in PEF greater than expected are associated with the development of frailty. Subsequent studies are encouraged to delve deeper into the connection between respiratory function and frailty in diverse contexts.


Asunto(s)
Fragilidad , Humanos , Estudios Longitudinales , Masculino , Femenino , Anciano , China/epidemiología , Ápice del Flujo Espiratorio , Estudios Transversales , Persona de Mediana Edad , Anciano de 80 o más Años , Anciano Frágil/estadística & datos numéricos , Prevalencia , Jubilación/estadística & datos numéricos
17.
Helicobacter ; 29(3): e13063, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38874128

RESUMEN

BACKGROUND: The overall benefits of the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population. MATERIALS AND METHODS: Decision trees and Markov models of H. pylori infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs -$6.46/QALY and -$24.75/LY, and screen-and-treat strategy costs -$3.3/QALY and -$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of H. pylori-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified. CONCLUSIONS: Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial H. pylori infection and also serves as an excellent reference for other highly infected societies.


Asunto(s)
Análisis Costo-Beneficio , Infecciones por Helicobacter , Humanos , Infecciones por Helicobacter/economía , Infecciones por Helicobacter/prevención & control , Infecciones por Helicobacter/diagnóstico , China/epidemiología , Helicobacter pylori , Años de Vida Ajustados por Calidad de Vida , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/prevención & control , Neoplasias Gástricas/economía , Femenino , Tamizaje Masivo/economía , Adulto , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/prevención & control , Enfermedades Gastrointestinales/economía , Anciano , Control de Infecciones/economía , Control de Infecciones/métodos , Úlcera Péptica/prevención & control , Úlcera Péptica/economía , Pueblos del Este de Asia
18.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900048

RESUMEN

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

19.
Inhal Toxicol ; 36(4): 275-281, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38836332

RESUMEN

Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.


Asunto(s)
Nanotubos de Carbono , Triterpenos Pentacíclicos , Neumonía , Transducción de Señal , Triterpenos , Animales , Masculino , Ratones , Antiinflamatorios/farmacología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/química , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Nanotubos de Carbono/toxicidad , FN-kappa B/metabolismo , Triterpenos Pentacíclicos/farmacología , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/prevención & control , Neumonía/metabolismo , Transducción de Señal/efectos de los fármacos , Triterpenos/farmacología
20.
Int J Ophthalmol ; 17(5): 838-844, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766334

RESUMEN

AIM: To report a technique used with intermittent sliding-lock-knot (ISLK) fixation for limbal conjunctival autografts in pterygium surgery and compared with those of routine intermittent (RI) fixation. METHODS: Consecutive patients with primary pterygium who had undergone pterygium excision combined with limbal conjunctival autograft transplantation between March 2021 and March 2022 at our institute were retrospectively analyzed. Primary outcome measures were mean duration of surgery and suture removal, degree of conjunctival hyperemia on postoperative day 1, pain score at suture removal, postoperative symptoms at 6mo, including conjunctival hyperemia, foreign body sensation, and graft stability. RESULTS: Ninety-eight patients underwent monocular surgery and were divided into ISLK (51 eyes) and RI (47 eyes) groups according to the type of conjunctiva autograft fixation method planned. There was no significant difference in mean duration of surgery between the two groups (18.59±2.39min vs 18.15±2.20min, P=0.417); however, compared to the RI group, shorter suture removal times were observed in the ISLK group [0.58min (0.42-0.87) vs 3.00min (2.21-4.15), P<0.001]. The degree of conjunctival hyperemia on postoperative day 1 was milder in the ISLK group (P<0.001). Pain scores at suture removal were lower in the ISLK group than in RI group [1 (0-3) vs 2 (1-4), P<0.001]. Postoperative symptoms at 6mo were comparable between the groups (P=0.487), with no recurrence. CONCLUSION: ISLK is an innovative method for limbal conjunctival autograft fixation after pterygium excision. Compared to RI fixation, ISLK facilitates suture removal and reduces discomfort, with comparable surgery duration and less conjunctival hyperemia.

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