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1.
Lancet Reg Health West Pac ; 49: 101090, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39381018

RESUMEN

The development of targeted drugs in the Eastern Asia region is going through a flourishing stage. With the continuous advancement of technology and medical research, biotechnology companies and research institutions in the region have made significant progress in cancer field. The Eastern Asian region not only actively participates in clinical trials, but is also committed to developing personalized medical plans to meet the diverse genotypes and phenotypes of patients. The governments and enterprises are increasingly valuing innovation, strengthening international cooperation, and promoting drug development. This paper summarizes the development of genetic testing technology, targeted drugs approval, ongoing promising clinical trials in the field of lung cancer and the important progress made by governments in the Eastern Asian region, and proposed key factors that will contribute to the promising future prospects in the region. The targeted drug market in the Eastern Asian region is expected to drive the medical field forward.

2.
BMC Cancer ; 24(1): 1223, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358733

RESUMEN

BACKGROUND: To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. METHODS: We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. RESULTS: The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults. CONCLUSION: Paediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.


Asunto(s)
Supervivientes de Cáncer , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Calidad de Vida , Radioterapia de Intensidad Modulada , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/psicología , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Adulto , Niño , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Adolescente , Persona de Mediana Edad , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/psicología , Adulto Joven , Anciano , Estado de Salud
3.
Artículo en Inglés | MEDLINE | ID: mdl-39446534

RESUMEN

Automated polyp segmentation from colonoscopy images is crucial for colorectal cancer diagnosis. The accuracy of such segmentation, however, is challenged by two main factors. First, the variability in polyps' size, shape, and color, coupled with the scarcity of well-annotated data due to the need for specialized manual annotation, hampers the efficacy of existing deep learning methods. Second, concealed polyps often blend with adjacent intestinal tissues, leading to poor contrast that challenges segmentation models. Recently, diffusion models have been explored and adapted for polyp segmentation tasks. However, the significant domain gap between RGB-colonoscopy images and grayscale segmentation masks, along with the low efficiency of the diffusion generation process, hinders the practical implementation of these models. To mitigate these challenges, we introduce the Highlighted Diffusion Model Plus (HDM+), a two-stage polyp segmentation framework. This framework incorporates the Highlighted Diffusion Model (HDM) to provide explicit semantic guidance, thereby enhancing segmentation accuracy. In the initial stage, the HDM is trained using highlighted ground-truth data, which emphasizes polyp regions while suppressing the background in the images. This approach reduces the domain gap by focusing on the image itself rather than on the segmentation mask. In the subsequent second stage, we employ the highlighted features from the trained HDM's U-Net model as plug-in priors for polyp segmentation, rather than generating highlighted images, thereby increasing efficiency. Extensive experiments conducted on six polyp segmentation benchmarks demonstrate the effectiveness of our approach.

4.
J Med Chem ; 67(20): 18412-18447, 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39361006

RESUMEN

Currently, there are no specific drugs for treating acute pancreatitis. Soluble epoxide hydrolase (sEH) inhibitors show promise, but face challenges like low blood drug concentrations and potential adverse effects on CYP enzymes and the human ether-a-go-go-related gene (hERG). In this study, an approach involving scaffold hopping and structure-activity guided optimization was employed to design a series of phenylquinoline-based sEH inhibitors. Among these compounds, DJ-53 exhibited potent in vitro and in vivo effects in alleviating pain and reducing inflammation. The in vivo mechanism of action involved inhibiting sEH enzyme activity, thereby increasing levels of anti-inflammatory epoxyeicosatrienoic acids (EETs) and decreasing levels of proinflammatory dihydroxyeicosatrienoic acids (DHETs). Importantly, DJ-53 showed exceptional oral bioavailability and pharmacokinetics, while avoiding inhibition of CYP enzymes or the hERG channel. These results highlight DJ-53's potential as a new lead compound for anti-inflammatory and analgesic applications and provide a safe and effective scaffold for developing sEH inhibitors.


Asunto(s)
Analgésicos , Inhibidores Enzimáticos , Epóxido Hidrolasas , Quinolinas , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Analgésicos/farmacología , Analgésicos/química , Analgésicos/síntesis química , Analgésicos/farmacocinética , Animales , Humanos , Relación Estructura-Actividad , Administración Oral , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacocinética , Inhibidores Enzimáticos/síntesis química , Quinolinas/farmacología , Quinolinas/química , Quinolinas/síntesis química , Quinolinas/farmacocinética , Antiinflamatorios/farmacología , Antiinflamatorios/farmacocinética , Antiinflamatorios/química , Antiinflamatorios/síntesis química , Masculino , Ratones , Dolor/tratamiento farmacológico , Descubrimiento de Drogas , Solubilidad , Ratas
5.
Anal Methods ; 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39446103

RESUMEN

Due to their wide applications, occurrence and "PFAS-like" environmental behaviors, ionic liquids (ILs) represent a new challenge for the environmental monitoring community, who require robust analytical methods that can determine accurately and efficiently their environmentally relevant concentrations. A new passive sampling method based on the diffusive gradients in thin films (DGT) technique was developed for the measurement of imidazole-based ILs in waters using a mixed-mode cation exchange (MCX) resin as the adsorbent. The selected binding gel had a high binding capacity (>170 µg per disc) for ILs. Diffusion coefficients measured using a diffusion cell correlated well with alkyl chain lengths (r2 = 0.95) and retention times (r2 = 0.88), providing a simple and rapid prediction approach for other ILs. The assembled MCX-DGT sampler exhibited a linear accumulation for at least 120 h. MCX-DGT also showed good performance under typical freshwater conditions (pH 5-8, ionic strength 0.001-0.01 M, and humic acid 0-5 mg L-1), while still being problematic for aquatic conditions with higher ionic strength (>0.1 M) or DOM (>10 mg L-1). Laboratory deployment (for up to 3 days) in spiked natural freshwater (SNW) resulted in linear mass uptakes for the short-chain ILs (C2-C8), and their DGT-measured concentrations agreed well with solution concentrations. However, MCX-DGT significantly overestimated the concentrations of the long-chain ILs (C10-C12) when deployed in SNW for one day or more, which is attributed to the strong competitive adsorption of the long-chain ILs by natural organic matter. In situ field evaluation along with grab sampling found no target ILs in a wastewater treatment plant and its receiving river, implying that these new chemicals might not be widely used in South China now. This is the first report on the DGT technique for ILs and might provide an effective tool for monitoring short chain length ILs in the aquatic environment in the near future.

6.
Natl Sci Rev ; 11(11): nwae247, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39440264

RESUMEN

Edge detection is a fundamental operation for feature extraction in image processing. The all-optical method has aroused growing interest owing to its ultra-fast speed, low energy consumption and parallel computation. However, current optical edge detection methods are generally limited to static devices and fixed functionality. Herein, we propose a fast-switchable scheme based on a ferroelectric liquid crystal topological structure. The self-assembled chiral lamellar superstructure, directed by the azimuthally variant photo-alignment agent, can be dynamically controlled by the polarity of the external electric field and respectively generates the vector beams with nearly orthogonal polarization distribution. Even after thousands of cycles, the horizontal and vertical edges of the object are selectively enhanced with an ultra-fast switching time of ∼57 µs. Broadband edge-enhanced imaging is efficiently demonstrated. This work extends the ingenious building of topological heliconical superstructures and offers an important glimpse into their potential in the emerging frontiers of optical computing for artificial intelligence.

7.
Chem Commun (Camb) ; 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39404007

RESUMEN

As a critical metabolite, the standardization of lactate quantification is increasingly crucial. Therefore, we developed LaconicSF, a lactate-responsive biosensor exhibiting exceptional specificity in lactate detection. LaconicSF enables efficient lactate quantification in CHO cell culture medium and holds potential as a user-friendly detection tool for lactate quantification in vitro.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39404814

RESUMEN

KEY POINTS: Omalizumab enables children who are intolerant to AIT to initiate AIT successfully. Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumab treatment. Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39374289

RESUMEN

The goal of RGB-Thermal (RGB-T) tracking is to utilize the synergistic and complementary strengths of RGB and TIR modalities to enhance tracking in diverse situations, with cross-modal interaction being a crucial element. Earlier methods often simply combine the features of the RGB and TIR search frames, leading to a coarse interaction that also introduced unnecessary background noise. Many other approaches sample candidate boxes from search frames and apply different fusion techniques to individual pairs of RGB and TIR boxes, which confines cross-modal interactions to local areas and results in insufficient context modeling. Additionally, mining video temporal contexts is also under-explored in RGB-T tracking. To alleviate these limitations, we propose a novel Template-Bridged Search region Interaction (TBSI) module that exploits templates as the medium to bridge the cross-modal interaction between RGB and TIR search regions by gathering and distributing target-relevant object and environment contexts. An Illumination Guided Fusion (IGF) module is designed to adaptively fuse RGB and TIR search region tokens with a global illumination factor. Furthermore, in the inference stage, we also propose an efficient Target-Preserved Template Updating (TPTU) strategy, leveraging the temporal context within video sequences to accommodate the target's appearance change. Our proposed modules are integrated into a ViT backbone for joint feature extraction, search-template matching, and cross-modal interaction. Extensive experiments on three popular RGB-T tracking benchmarks demonstrate our method achieves new state-of-the-art performances. Code is available at https://github.com/RyanHTR/TBSI.

11.
Angew Chem Int Ed Engl ; : e202413594, 2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39394806

RESUMEN

Stabilizing specific intermediates to produce CH4 remains a main challenge in solar-driven CO2 reduction. Herein, g-C3N4 is modified with saturated and lacunary phosphotungstates (PWx, x = 12, 11, 9) to tailor the CO2 reduction pathway to yield CH4 in high selectivity. Increased lacuna of phosphotungstates leads to higher CH4 yield and selectivity, with a superior CH4 selectivity of 80% and 40.8 µmol·g-1·h-1 evolution rate for PW9/g-C3N4. Conversely, g-C3N4 and PWx alone show negligible CH4 production. The conversion of CO2 to CH4 follows a tandem catalytic process. CO2 is initially activated on g-C3N4 to form *CO intermediates, meanwhile photogenerated electrons derived from g-C3N4 transfer to PWx. Then the reduced PWx captures *CO, which is subsquently hydrogenated to CH4. With the injection of two photogenerated electrons, PW9 is capable of adsorbing and activating *CO. However, the reduced PW12 and PW11 are incapable of adsorbing *CO due to the small energy of occupied molecular orbitals, which is the reason for the poorer activity of PWx/g-C3N4 (x = 12, 11) compared with that of PW9/g-C3N4. This work provides new insights to regulate highly selective CO2 photoreduction to CH4 by utilizing lacuna of polyoxometalates to enhance the interaction of metals in polyoxometalates with key intermediates.

12.
Immunol Lett ; 270: 106934, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39395727

RESUMEN

Mas-related G protein-coupled receptor X2 (MRGPRX2) is a newly identified receptor on mast cells that contribute to IgE-independent pseudo-allergy. Ursolic acid (UA), a pentacyclic triterpenoid, has been reported for its anti-allergy effects. However, the protective mechanism against pseudo-allergic reactions remains unclear. This study aims to investigate the effects of UA on pseudo-allergic reactions both in vivo and in vitro, focusing on the therapeutical mechanism underlying its effect on mast cells. In present study, UA reduced degranulation and chemokines production induced by MRGPRX2 agonists, including compound 48/80 (C48/80) and substance P (SP), in LAD2 cells in vitro. UA also alleviated C48/80 and SP-induced systemic anaphylaxis and passive cutaneous anaphylaxis (PCA) in vivo. Furthermore, UA demonstrated strong binding affinity to the MRGPRX2 protein, leading to a decrease in calcium influx in both LAD2 cells and MRGPRX2-HEK293 cells stimulated with C48/80 and SP. Moreover, UA effectively suppressed phosphorylation levels within phospholipase C-γ (PLCγ) pathway and nuclear factor kappa-B (NF-κB) pathway of MRGPRX2 downstream proteins. Our findings indicated that UA exerts an attenuating effect in pseudo-allergic reactions by suppressing MRGPRX2-mediated mast cell activation, targeting PLCγ pathway and NF-κB pathway. These results suggest that UA may serve as a promising therapeutic agent for MRGPRX2-dependent pseudo-allergic reactions.

13.
Eur J Med Chem ; 280: 116937, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39413443

RESUMEN

There are few reports on soluble epoxide hydrolase (sEH) structure-activity relationship studies using natural product-based scaffolds. In this study, we discovered that C-30 urea derivatives of glycyrrhetinic acid such as 33, rather than C-20/C-3 urea derivatives, possess in vitro sEH inhibitory capabilities. Furthermore, we explored the impact of stereoconfigurations at C-3 and C-18 positions, and glycosidic bonds at the 3-OH on the compound's activity. Consequently, a glycoside of 33, specifically 49Cα containing alpha-oriented mannose, exhibited promising in vivo efficacy in alleviating carrageenan-induced paw edema and acetic acid-induced writhing. Meanwhile, 49Cα demonstrated potential in mitigating acute pancreatitis by modulating the ratios of anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory dihydroxyeicosatrienoic acids (DHETs). The co-crystal structure of sEH in complex with 49Cα revealed that the N-tetrahydropyranylmethylene urea hydrogen bonded with the residues within the sEH tunnel, contrasting with the mannose component that extended beyond the tunnel's confines. Our findings highlight 49Cα (coded LQ-38) as a promising candidate for anti-inflammatory and analgesic effects, and pave the way for the future rational design of triterpenoid-based sEH inhibitors.

14.
Clin Lung Cancer ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39424513

RESUMEN

INTRODUCTION: Osimertinib, the 3rd generation EGFR-TKI, has emerged as standard first-line treatment for patients with advanced EGFR mutated nonsmall cell lung cancer (NSCLC). Patients with exon 21 L858R mutation showed lower efficacy with EGFR-TKIs than those with 19Del mutation, even with osimertinib, it remains an unmet medical need to further improve the efficacy in L858R population. We present the rationale and design for FLAIR (NCT04988607), which will investigate the efficacy and safety of osimertinib plus bevacizumab versus osimertinib monotherapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation. MATERIALS AND METHODS: FLAIR is a prospective, multicenter, randomized, open label study, which is initiated by Chinese Thoracic Oncology Group (CTONG2002). Patients age ≥18 years with primary recurrent or metastatic nonsquamous NSCLC who are treatment-naïve with documented EGFR exon 21 L858R mutation is eligible. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until progression or another discontinuation criterion is met. The primary endpoint is investigator-assessed progression free survival (PFS). Secondary endpoints include: overall survival rate at 24 months, time to treatment failure (TTF), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), central nervous system (CNS) PFS, CNS ORR and safety. RESULTS: FLAIR has completed the enrollment, and results are expected in the fourth quarter of 2025 (depending on the actual event rate). CONCLUSIONS: This study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

15.
Phytomedicine ; 135: 156117, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39426255

RESUMEN

BACKGROUND: Z-Ligustilide (ZL) is an essential phthalide found in Ligusticum chuanxiong Hort, a commonly used traditional Chinese medicine for treating atherosclerosis (AS) clinically. ZL has been shown to be effective in treating AS. However, the underlying mechanism of ZL against AS and its potential targets remain elusive. PURPOSE: The purpose of this research was to assess the influence of ZL on AS and explore the role of the gut microbiome in mediating this effect. METHODS: A well-established AS mouse model, apolipoprotein E deficient (ApoE-/-) mice was used to examine the effects of ZL on AS, inflammation, and the intestinal barrier. To analyze the changes in gut microbial community, we employed the 16S rRNA gene sequencing. Antibiotic cocktail and fecal microbiota transplantation (FMT) were employed to clarify the contribution of the gut microbiota to the anti-AS effects of ZL. The mechanism through which ZL provided protective effects on AS and the intestinal barrier was explored by untargeted metabolomics, as well as by validating the involvement of cannabinoid receptor 2 (CB2R) in mice and Caco-2 cells. RESULTS: Oral administration of ZL inhibited the development of atherosclerotic lesions, improved plaque stability, inhibited the increase in serum and atherosclerotic inflammation, and improved intestinal barrier function. Fecal bacteria from ZL-treated mice induced similar beneficial effects on AS and the intestinal barrier. We used 16S RNA gene sequencing to reveal a significant increase in Rikenella abundance in both ZL-treated mice and ZL-FMT mice, which was associated with the beneficial effects of ZL. Further function prediction analysis of the gut microbiota and CB2R antagonist intervention experiment in mice and Caco-2 cells showed that the activation of CB2R resulted in the enhancement of the intestinal barrier by ZL. Furthermore, the analysis of metabolomic profiling revealed the enrichment of capsaicin upon ZL treatment, which induced the activation of CB2R in human colon epithelial cells. CONCLUSION: Our study is the first to demonstrate that oral treatment with ZL has the potential to alleviate AS by reducing inflammation levels and enhancing the intestinal barrier function. This mechanism relies on the gut microbiota in a CB2R-dependent manner, suggesting promising strategies and ideas for managing AS. This study provides insights into a novel mechanism for treating AS with ZL.

17.
Stress Biol ; 4(1): 44, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39400641

RESUMEN

Ligusticum sinense cv. Chuanxiong (L. Chuanxiong), one of the widely used traditional Chinese medicines (TCM), is currently facing the problem of excessive cadmium (Cd) content. This problem has significantly affected the quality and safety of L. Chuanxiong and become a vital factor restricting its clinical application and international trade development. Currently, to solve the problem of excessive Cd, it is essential to research the response mechanisms of L. Chuanxiong to Cd stress. However, there are few reports on its physiological and biochemical responses under Cd stress. In this study, we conducted the hydroponic experiment under 25 µM Cd stress, based on the Cd content of the genuine producing areas soil. The results showed that 25 µM Cd stress not only had no significant inhibitory effect on the growth of L. Chuanxiong seedlings but also significantly increased the chlorophyll a content (11.79%) and root activity (51.82%) compared with that of the control, which might be a hormesis effect. Further results showed that the absorption and assimilation of NH4+ increased in seedlings under 25 µM Cd stress, which was associated with high photosynthetic pigments. Here, we initially hypothesized and confirmed that Cd exceedance in the root system of L. Chuanxiong was due to the thickening of the root cell wall, changes in the content of the cell wall components, and chelation of Cd by GSH. There was an increase in cell wall thickness (57.64 %) and a significant increase in cellulose (25.48%) content of roots under 25 µM Cd stress. In addition, L. Chuanxiong reduced oxidative stress caused by 25 µM Cd stress mainly through the GSH/GSSG cycle. Among them, GSH-Px (48.26%) and GR (42.64%) activities were significantly increased, thereby maintaining a high GSH/GSSG ratio. This study preliminarily reveals the response of L. Chuanxiong to Cd stress and the mechanism of Cd enrichment. It provides a theoretical basis for solving the problem of Cd excessive in L. Chuanxiong.

18.
Int J Mol Sci ; 25(19)2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39408861

RESUMEN

As the sole producers of insulin under physiological conditions, the normal functioning of pancreatic ß cells is crucial for maintaining glucose homeostasis in the body. Due to the high oxygen and energy demands required for insulin secretion, hypoxia has been shown to play a critical role in pancreatic ß-cell dysfunction. Lipid metabolism abnormalities, a common metabolic feature in type 2 diabetic patients, are often accompanied by tissue hypoxia caused by metabolic overload and lead to increased free fatty acid (FFA) levels. However, the specific mechanisms underlying FFA-induced ß-cell dysfunction remain unclear. Nicotinamide mononucleotide (NMN), a naturally occurring bioactive nucleotide, has garnered significant attention in recent years for its effectiveness in replenishing NAD+ and alleviating various diseases. Nevertheless, studies exploring the mechanisms through which NMN influences ß-cell dysfunction remain scarce. In this study, we established an in vitro ß-cell dysfunction model by treating INS-1 cells with palmitate (PA), including control, PA-treated, and PA combined with NMN or activator/inhibitor groups. Compared to the control group, cells treated with PA alone showed significantly reduced insulin secretion capacity and decreased expression of proteins related to the NAD+/AMPK/SIRT1/HIF-1α pathway. In contrast, NMN supplementation significantly restored the expression of pathway-related proteins by activating NAD+ and effectively improved insulin secretion. Results obtained using HIF-1α and AMPK inhibitors/activators further supported these findings. In conclusion, our study demonstrates that NMN reversed the PA-induced downregulation of the NAD+/AMPK/SIRT1/HIF-1α pathway, thereby alleviating ß-cell dysfunction. Our study investigated the mechanisms underlying PA-induced ß-cell dysfunction, examined how NMN mitigates this dysfunction and offered new insights into the therapeutic potential of NMN for treating ß-cell dysfunction and T2DM.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Ácidos Grasos no Esterificados , Subunidad alfa del Factor 1 Inducible por Hipoxia , Células Secretoras de Insulina , NAD , Mononucleótido de Nicotinamida , Transducción de Señal , Sirtuina 1 , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mononucleótido de Nicotinamida/farmacología , Mononucleótido de Nicotinamida/metabolismo , Sirtuina 1/metabolismo , Animales , Ácidos Grasos no Esterificados/metabolismo , NAD/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Insulina/metabolismo , Humanos , Secreción de Insulina/efectos de los fármacos
19.
Artículo en Inglés | MEDLINE | ID: mdl-39322652

RESUMEN

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

20.
Zhongguo Gu Shang ; 37(9): 862-9, 2024 Sep 25.
Artículo en Chino | MEDLINE | ID: mdl-39342469

RESUMEN

OBJECTIVE: To compare clinical efficacy of robot-assisted (RA) and remote sensing navigation alignment (RSNA) system-assisted total knee arthroplasty (TKA). METHODS: From March 2023 to June 2023, 60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis (KOA) were admitted and divided into RSNA group and RA group according to different treatment methods, with 30 patients in each group. There were 5 males and 25 females in RSNA group, aged from 56 to 81 years old with an average of(66.33±7.16) years old;body mass index(BMI) ranged from 19.87 to 38.54 kg·m-2 with an average of (28.40±6.18) kg·m-2;the courses of disease ranged from 5 to 36 months with an average of (18.20±8.98) months; RSNA system was used to assist the positioning of osteotomy. There were 7 males and 23 females in RA group, aged from 55 to 82 years old with an average of (67.83±8.61) years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an average of (28.01±4.89) kg·m-2; the courses of disease ranged from 3 to 33 months with an average of (17.93±9.20) months;RA was performed. Operation time, incision length, latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups. Hip-knee ankle angle (HKAA), HKAA deviation, lateral distal femoral angle ( LDFA), medial proximal tibial angle (MPTA) and posterior tibial slope (PTS) were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society score (KSS) were used to evaluate functional recovery before operation, 3 and 6 months after operation. RESULTS: The operation was performed successfully in both groups, and there were no serious complications such as vascular and nerve injury during operation. The wound healed well at stageⅠafter operation, and the follow-up time was 6 months. The operation time, latent blood loss at 2 weeks after operation and incision length in RSNA group were (94.35±5.75) min, (130.54±17.53) ml and (14.73±2.14) cm, respectively;while (102.57±6.88) min, (146.33±19.47) ml and (16.78±2.32) cm in RA group, respectively. RSNA group was better than RA group (P<0.05). No deep vein thrombosis occurred in both groups at 2 weeks after operation, 5 patients occurred intermuscular vein thrombosisin in RSNA group and 8 patients in RA group, the difference was not statistically significant (P>0.05). In RSNA group, HKAA, LDFA and MPTA were (173.00±5.54) °, (86.96±3.45) °, (82.79±3.35) ° before operation, and (178.34±1.85) °, (89.92±0.42) °, (89.84±0.73) ° at 1 week after operation, respectively. In RA group, HKAA, LDFA and MPTA were (173.31±6.48) °, (87.15±3.40) ° and (82.99±3.05) ° before operation, and (178.52±1.79) °, (90.03±0.39) ° and (90.15±0.47) ° at 1 week after operation, respectively. HKAA, LDFA and MPTA were significantly improved in both groups at 1 week after operation (P<0.05). There were no significant difference in HKAA, LDFA, MPTA and PTS between two groups before operation and 1 week after operation (P>0.05). There was no significant difference in deviation distribution of HKAA at 1 week after operation (χ2=2.611, P=0.456). There were no significant difference in WOMAC and KSS between two groups before operation, 3 and 6 months after operation (P>0.05), and postoperative WOMAC and KSS at 3 and 6 months between two groups were improved compared with those before operation (P<0.05). CONCLUSION: Both RA and RSNA system assisted TKA could obtain accurate osteotomy, RA has higher surgical accuracy, RSNA system assisted operation has less trauma, and operation is simpler.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Femenino , Artroplastia de Reemplazo de Rodilla/métodos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Procedimientos Quirúrgicos Robotizados/métodos , Osteoartritis de la Rodilla/cirugía , Tecnología de Sensores Remotos/métodos , Tecnología de Sensores Remotos/instrumentación , Sistemas de Navegación Quirúrgica
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