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1.
Lancet Neurol ; 23(3): 267-276, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38365379

RESUMO

BACKGROUND: Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation. In addition to corticosteroids, azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America. We aimed to evaluate the comparative effectiveness of these two drugs, and to assess the effect of the dose and duration of treatment. METHODS: We did a prospective cohort study at 19 academic centres in Canada and the USA. We included patients (aged ≥18 years) with autoimmune myasthenia gravis, who were never treated with immunosuppressants. Treating clinicians determined the choice of medication, dose, follow-up intervals, and drug monitoring. Outcome measures and adverse events were recorded at each visit. We assessed two co-primary outcomes. The first was the patient-reported Myasthenia Gravis-Quality of Life 15-revised (MGQOL-15r) score, measured as the mean change from treatment initiation to the follow-up visit with the lowest score. A clinically meaningful reduction (CMR) in MGQOL-15r was defined as a 5-point decrease. The second was a composite clinical outcome of disease improvement (Myasthenia Gravis Foundation of America Post-Intervention Status Minimal Manifestations or better) and low adverse event burden (defined as grade ≤1 Common Terminology Criteria for Adverse Events). We also compared these outcomes in patients receiving an adequate dose and duration of azathioprine (≥2 mg/kg per day for at least 12 months) or mycophenolate mofetil (≥2 g per day for at least 8 months) and a lower dose or shorter duration of these agents. We used propensity score weighting with generalised linear regression models. This study is registered with ClinicalTrials.gov (NCT03490539). FINDINGS: Between May 1, 2018, and Aug 31, 2020, 167 patients were enrolled; 85 did not receive azathioprine or mycophenolate mofetil and were excluded. Four were excluded from outcome analyses because they had scores of 0 on an outcome measure at treatment initiation. Of the 78 patients included in analyses, 47 received mycophenolate mofetil (median follow-up 25 months [IQR 13·5-31·5]) and 31 received azathioprine (median follow-up 20 months [IQR 13-30]). The mean change in MG-QOL15r was -10·4 (95% CI -18·9 to -1·3) with mycophenolate mofetil and -6·8 (-17·2 to 3·6) with azathioprine (mean difference -3·3, 95% CI -7·7 to 1·2; p=0·15). 38 (81%) of 47 patients receiving mycophenolate mofetil and 18 (57%) of 31 receiving azathioprine had a CMR in MG-QOL15r (risk difference 24·0%; 95% CI -0·2 to 48·0; p=0·052). The clinical composite outcome was achieved in 22 (47·7%) of 47 patients who received mycophenolate mofetil and nine (28·1%) of 31 who received azathioprine (risk difference 19·6%, 95% CI -4·9 to 44·2; p=0·12). Descriptive analysis did not find a difference in the proportion of patients reaching a CMR in MG-QOL15r between the adequate dose and duration group and the lower dose or shorter duration group. Adverse events occurred in 11 (32%) of 34 patients who received azathioprine and nine (19%) of 48 who received mycophenolate mofetil. The most frequent adverse events were hepatotoxicity with azathioprine (five [15%] of 34) and gastrointestinal disturbances (seven [15%] of 48) with mycophenolate mofetil. There were no study-related deaths. INTERPRETATION: More than half of patients treated with azathioprine and mycophenolate mofetil felt their quality of life improved; no difference in clinical outcomes was noted between the two drugs. Adverse events associated with azathioprine were potentially more serious than those with mycophenolate mofetil, although mycophenolate mofetil is teratogenic. Lower than recommended doses of azathioprine might be effective, with reduced dose-dependent adverse events. More comparative effectiveness studies are required to inform treatment choices in myasthenia gravis. FUNDING: Patient-Centered Outcomes Research Institute, Myasthenia Gravis Foundation of America.


Assuntos
Azatioprina , Miastenia Gravis , Humanos , Adolescente , Adulto , Azatioprina/uso terapêutico , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Imunossupressores/efeitos adversos , Miastenia Gravis/tratamento farmacológico
2.
Aging (Albany NY) ; 162024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364236

RESUMO

BACKGROUND: Blood-brain barrier (BBB) could aggravate cerebral ischemia injury. Dexmedetomidine (Dex) has been believed to play a protective role in cerebral ischemia injury-induced BBB injury. METHODS: Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) models were established to simulate cerebral ischemia injury. Animal experiments included 4 groups, Sham, MCAO, MCAO+Dex, MCAO+Dex+sh-CCN1. Generally applicable gene set enrichment analysis was performed to analyze gene expression difference. Total collagen content and Evans blue staining were performed to measure infarct ratio and BBB breakdown, respectively. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively. The levels of IL-1ß, TNF-α, and IL-6 in serum were measured with commercial ELISA kits. RESULTS: Dex greatly promoted the expression level of CCN1. Dex suppressed cerebral ischemia injury, increased tight junction protein expression, improved the memory ability and neurological function of MCAO rats through targeting CCN1. The significant increase of inflammatory factors in the serum of MCAO rats were suppressed by Dex. Dex suppressed OGD induced increase of HRP permeability and promoting tight junction protein expression in vitro through regulating CCN1. The neurological function evaluation was performed with Neurological Severity Score (NSS) and Longa Score Scale. CONCLUSIONS: Dex could remarkably alleviate cerebral ischemia injury by inhibiting BBB breakdown, inflammatory response, and promoting neurological function and tight junction protein expression via up-regulating CCN1. This study might provide a novel therapeutic target for the prevention and treatment of cerebral ischemia injury-induced BBB.

3.
Opt Lett ; 49(4): 1069-1072, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359255

RESUMO

This Letter proposes a high-security and high-order signal transmission method that is based on delta-sigma modulation (DSM) and discrete memristive-enhanced chaos (DMEC). We employ the DMEC for the encryption of DSM signals to achieve a key space of 1098 in size. Moreover, we demonstrated a high-security transmission of 16384QAM signals using the DSM over a 25 km single-mode fiber in the intensity-modulated direct detection (IMDD) system. The experimental results show that the proposed ultrahigh-order transmission scheme based on DMEC and DSM guarantees high signal transmission performances with improved security and a key sensitivity level of 10-17.

4.
J Ethnopharmacol ; : 117913, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38360380

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated. AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis. MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model. RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor. CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

5.
Fish Shellfish Immunol ; 147: 109443, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38354964

RESUMO

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air ♀ × Apu ♂) and Api (Apu ♀ × Air ♂). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.

6.
J Control Release ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367864

RESUMO

Peripheral nerve injury (PNI) and the limitations of current treatments often result in incomplete sensory and motor function recovery, which significantly impact the patient's quality of life. While exosomes (Exo) derived from stem cells and Schwann cells have shown promise on promoting PNI repair following systemic administration or intraneural injection, achieving effective local and sustained Exo delivery holds promise to treat local PNI and remains challenging. In this study, we developed Exo-loaded decellularized porcine nerve hydrogels (DNH) for PNI repair. We successfully isolated Exo from differentiated human adipose-derived mesenchymal stem cells (hADMSC) with a Schwann cell-like phenotype (denoted as dExo). These dExo were further combined with polyethylenimine (PEI), and DNH to create polyplex hydrogels (dExo-loaded pDNH). At a PEI content of 0.1%, pDNH showed cytocompatibility for hADMSCs and supported neurite outgrowth of dorsal root ganglions. The sustained release of dExos from dExo-loaded pDNH persisted for at least 21 days both in vitro and in vivo. When applied around injured nerves in a mouse sciatic nerve crush injury model, the dExo-loaded pDNH group significantly improved sensory and motor function recovery and enhanced remyelination compared to dExo and pDNH only groups, highlighting the synergistic regenerative effects. Interestingly, we observed a negative correlation between the number of colony-stimulating factor-1 receptor (CSF-1R) positive cells and the extent of PNI regeneration at the 21-day post-surgery stage. Subsequent in vitro experiments demonstrated the potential involvement of the CSF-1/CSF-1R axis in Schwann cells and macrophage interaction, with dExo effectively downregulating CSF-1/CSF-1R signaling.

7.
PLoS One ; 19(2): e0297133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38300979

RESUMO

To analyze the post-COVID-19 construction and management of fever clinics targeted to prevention and control of healthcare-associated respiratory viral infections in medical institutions at all levels in China, and to provide a basis for promoting their standardized construction, we conducted this survey on the construction of fever clinics in 429 medical institutions of Jiangsu Province from July to December 2020. Contents of the questionnaire included the general situation of medical institutions, the construction status and future construction plans of fever clinics. We find the construction rate of fever clinic in medical institutions of Jiangsu province was 75.3%. All construction indicators, quality management systems and processes fail to fully meet the requirements of documents and standards. Jiangsu province actively promotes the construction of fever clinic layout, but there is still a gap with the construction standard. As a result, it is necessary to further promote standardized construction of fever clinic, and necessary financial input should be increased to expand all constructions of fever clinic in primary medical institutions.


Assuntos
COVID-19 , Febre , Humanos , Inquéritos e Questionários , China/epidemiologia , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Atenção à Saúde
8.
Nat Commun ; 15(1): 1295, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38346953

RESUMO

Two-dimensional (2D) superlattices, formed by stacking sublattices of 2D materials, have emerged as a powerful platform for tailoring and enhancing material properties beyond their intrinsic characteristics. However, conventional synthesis methods are limited to pristine 2D material sublattices, posing a significant practical challenge when it comes to stacking chemically modified sublattices. Here we report a chemical synthesis method that overcomes this challenge by creating a unique 2D graphene superlattice, stacking graphene sublattices with monodisperse, nanometer-sized, square-shaped pores and strategically doped elements at the pore edges. The resulting graphene superlattice exhibits remarkable correlations between quantum phases at both the electron and phonon levels, leading to diverse functionalities, such as electromagnetic shielding, energy harvesting, optoelectronics, and thermoelectrics. Overall, our findings not only provide chemical design principles for synthesizing and understanding functional 2D superlattices but also expand their enhanced functionality and extensive application potential compared to their pristine counterparts.

9.
Adv Mater ; : e2312094, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320173

RESUMO

Intelligent vision necessitates the deployment of detectors that are always-on and low-power, mirroring the continuous and uninterrupted responsiveness characteristic of human vision. Nonetheless, contemporary artificial vision systems attain this goal by the continuous processing of massive image frames and executing intricate algorithms, thereby expending substantial computational power and energy. In contrast, biological data processing, based on event-triggered spiking, has higher efficiency and lower energy consumption. Here, this work proposes an artificial vision architecture consisting of spiking photodetectors and artificial synapses, closely mirroring the intricacies of the human visual system. Distinct from previously reported techniques, the photodetector is self-powered and event-triggered, outputting light-modulated spiking signals directly, thereby fulfilling the imperative for always-on with low-power consumption. With the spiking signals processing through the integrated synapse units, recognition of graphics, gestures, and human action has been implemented, illustrating the potent image processing capabilities inherent within this architecture. The results prove the 90% accuracy rate in human action recognition within a mere five epochs utilizing a rudimentary artificial neural network. This novel architecture, grounded in spiking photodetectors, offers a viable alternative to the extant models of always-on low-power artificial vision system.

10.
BMJ ; 384: e077724, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331452
11.
BMC Med Genomics ; 17(1): 49, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331768

RESUMO

BACKGROUND: Pathway mutations have been calculated to predict the poor prognosis and immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC). To uncover the unique markers predicting prognosis and immune therapy response, the accurate quantification of pathway mutations are required to evaluate epithelial-mesenchymal transition (EMT) and immune escape. Yet, there is a lack of score to accurately quantify pathway mutations. MATERIAL AND METHODS: Firstly, we proposed Individualized Weighted Hallmark Gene Set Mutation Burden (IWHMB, https://github.com/YuHongHuang-lab/IWHMB ) which integrated pathway structure information and eliminated the interference of global Tumor Mutation Burden to accurately quantify pathway mutations. Subsequently, to further elucidate the association of IWHMB with EMT and immune escape, support vector machine regression model was used to identify IWHMB-related transcriptomic features (IRG), while Adversarially Regularized Graph Autoencoder (ARVGA) was used to further resolve IRG network features. Finally, Random walk with restart algorithm was used to identify biomarkers for predicting ICI response. RESULTS: We quantified the HNSCC pathway mutation signatures and identified pathway mutation subtypes using IWHMB. The IWHMB-related transcriptomic features (IRG) identified by support vector machine regression were divided into 5 communities by ARVGA, among which the Community 1 enriching malignant mesenchymal components promoted EMT dynamically and regulated immune patterns associated with ICI responses. Bridge Hub Gene (BHG) identified by random walk with restart was key to IWHMB in EMT and immune escape, thus, more predictive for ICI response than other 70 public signatures. CONCLUSION: In summary, the novel pathway mutation scoring-IWHMB suggested that the elevated malignancy mediated by pathway mutations is a major cause of poor prognosis and immunotherapy failure in HNSCC, and is capable of identifying novel biomarkers to predict immunotherapy response.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Mutação , Prognóstico , Biomarcadores Tumorais/genética , Imunoterapia , Transição Epitelial-Mesenquimal/genética
12.
J Ethnopharmacol ; 325: 117897, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38336180

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Quhan Zhiwang decoction (BQZD), a formula in traditional Chinese medicine (TCM), effectively delays bone destruction in rheumatoid arthritis (RA) patients. However, its chemical constituents, absorbed components, and metabolites remain unrevealed, and its mechanism in treating bone destruction in RA needs further investigation. AIM OF THE STUDY: Our objective is to identify the chemical constituents, absorbed components, and metabolites of BQZD and explore the potential mechanisms of BQZD in treating bone destruction in RA. MATERIALS AND METHODS: This study systematically identified the chemical constituents, absorbed components, and metabolites of BQZD using ultra-performance liquid chromatography with Q-Exactive Orbitrap mass spectrometry combined with parallel reaction monitoring. The absorbed components and metabolites were subjected to network pharmacology analysis to predict the potential mechanisms of BQZD in treating bone destruction in RA. The in vivo anti-osteoclastogenic and underlying mechanism were further verified in collagen-induced arthritis (CIA) rats. RESULTS: A total of 182 compounds were identified in BQZD, 27 of which were absorbed into plasma and organs and 42 metabolites were identified in plasma and organs. The KEGG analysis revealed that MAPK signaling pathway was highly prioritized. BQZD treatment attenuated paw swelling and the arthritis index; suppressed synovial hyperplasia, bone destruction, and osteoclast differentiation; and inhibited the levels of TNF-α, IL-1ß, and IL-6 in CIA rats. Mechanically, BQZD significantly decreased the protein expression levels of TRAF6, NFATc1, p-JNK, and p-p38, which might be related to 9 absorbed components and 1 metabolite. CONCLUSION: This study revealed the key active components and metabolites of BQZD. BQZD exhibits bone-protective effects via TRAF6/p38/JNK MAPK pathway, which may be associated with 9 absorbed components and 1 metabolite.

13.
Curr Med Chem ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38357947

RESUMO

BACKGROUND: Pyroptosis, a cell death process triggered by chemotherapy drugs, has emerged as a highly promising mechanism for combating tumors in recent years. As the lead of new drugs, natural products play an important role in the discovery of anticancer drugs. Compared to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior safety profile. Among a series of MFHNP molecular skeletons, this study found that only benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity of 1 remains to be improved. AIMS: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by modifying the chalcone structure. METHODS: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis, several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer activity was tested by MTT assay, and morphological indications of pyroptosis were observed in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore, to improve the activity of the chalcone skeleton, the anticancer group 3,4,5- trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed, synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally, a quantitative structure-activity relationship (QSAR) model was established using the eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore. Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular mechanisms of pyroptosis induced by the active compound. RESULTS: α, ß-unsaturated ketone was the functional group of the chalcone skeleton and played a pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients (R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft tumors. CONCLUSION: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis axis and is a kind of promising pyroptosis inducer.

14.
J Dent Sci ; 19(1): 411-418, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303820

RESUMO

Background/purpose: Proper implant-ridge classification is crucial for developing a dental implant treatment plan. This study aimed to verify the ability of MobileNet, an advanced deep learning model characterized by a lightweight architecture that allows for efficient model deployment on resource-constrained devices, to identify the implant-ridge relationship. Materials and methods: A total of 630 cone-beam computerized tomography (CBCT) slices from 412 patients were collected and manually classified according to Terheyden's definition, preprocessed, and fed to MobileNet for training under the conditions of limited datasets (219 slices, condition A) and full datasets (630 cases) without and with automatic gap filling (conditions B and C). Results: The overall model accuracy was 84.00% in condition A and 95.28% in conditions B and C. In condition C, the accuracy rates ranged from 94.00 to 99.21%, with F1 scores of 89.36-100.00%, and errors due to unidentifiable bone-implant contact and miscellaneous reasons were eliminated. Conclusion: The MobileNet architecture was able to identify the implant-ridge classification on CBCT slices and can assist clinicians in establishing a reliable preoperative diagnosis and treatment plan for dental implants. These results also suggest that artificial intelligence-assisted implant-ridge classification can be performed in the setting of general dental practice.

15.
Front Public Health ; 12: 1295924, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327571

RESUMO

Purpose: Recent studies have shown that physical activity (PA) levels are low among children and adolescents globally. In order to reverse this trend, PA interventions are increasingly favoured. The school setting is the ideal place to address the issues that many children face. The purpose of this study was to (a) The primary focus of this study is to delve into the mediating role played by school-based rope skipping sports participation (SRSP) in the connection between social support and moderate to high-intensity physical activity (MVPA) among school children. (b) Additionally, this research aims to examine the moderating effect of within this pathway. Methods: We conducted a survey involving 721 adolescents residing in Changsha City. The participants' ages ranged from 8 to 12 years, with an average age of 9.84 ± 1.535 years. Out of these participants, 406 were boys, and 315 were girls. To assess variables such as social support and autonomous motivation, we employed standardized measurement scales. Subsequently, we analyzed the collected data using various statistical methods, including independent s-amples t-tests, bivariate correlation analysis, descriptive statistical analysis, structural equation modeling (SEM), and the Johnson-Neyman method. Results: An independent samples t-test revealed a statistically significant difference in MVPA between genders (p = 0.003 < 0.05), with boys exhibiting a higher level of engagement in MVPA compared to girls, Correlation analysis revealed significant positive associations among several key variables. Specifically, social support demonstrated a noteworthy positive correlation with autonomous motivation (r = 0.331, p < 0.01) as well as school children's engagement in MVPA (r = 0.308, p < 0.01). Moreover, autonomous motivation displayed a significant positive correlation with school children's involvement in MVPA (r = 0.459, p < 0.01). The moderating analysis revealed a significant influence of the interaction between increased participation in and social support on school children's engagement in MVPA. Conclusion: Social support and autonomy support have been proven effective in enhancing school children's engagement in MVPA. They exert their influence indirectly by fostering autonomous motivation. Notably, robust social support can significantly benefit MVPA school children with high activity requirements, particularly those regularly engaged in MVPA during the school day.


Assuntos
Motivação , Esportes , Criança , Adolescente , Humanos , Masculino , Feminino , Comportamento Infantil , Exercício Físico , Apoio Social
16.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38328082

RESUMO

Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/- host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.

17.
World J Clin Cases ; 12(4): 835-841, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38322693

RESUMO

BACKGROUND: Presently, there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). While vitamin K antagonists are the preferred choice for oral blood thinning, determining the best course of blood-thinning medication remains challenging. It is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating LVT. This study significantly contributes to the medical community. CASE SUMMARY: The blood-thinning treatment of a patient with AMI and LVT was analyzed. Triple blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g, daily clopidogrel hydrogen sulfate at 75 mg, and dabigatran etexilate at 110 mg twice daily. After 15 d, the patient's LVT did not decrease but instead increased. Clinical pharmacists comprehensively analyzed the cases from the perspective of the patient's disease status and drug interaction. The drug regimen was reformulated for the patient, replacing dabigatran etexilate with warfarin, and was administered for six months. The clinical pharmacist provided the patient with professional and standardized pharmaceutical services. The patient's condition was discharged after meeting the international normalized ratio value (2-3) criteria. The patient fully complied with the follow-up, and the time in the therapeutic range was 78.57%, with no serious adverse effects during pharmaceutical monitoring. CONCLUSION: Warfarin proves to be an effective drug for patients with AMI complicated by LVT, and its blood-thinning course lasts for six months.

18.
Nat Commun ; 15(1): 1131, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326351

RESUMO

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.


Assuntos
Inteligência Artificial , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Radiologistas , Neoplasias Hepáticas/diagnóstico por imagem
19.
Ther Adv Respir Dis ; 18: 17534666241228159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327061

RESUMO

BACKGROUND: Pediatric bronchiectasis is a common respiratory disease in children. The use of video-assisted thoracoscopic surgery (VATS) for its treatment remains controversial. OBJECTIVES: The objective of our study was to compare and analyze the clinical efficacy of thoracoscopic surgery and thoracotomy in the treatment of pediatric bronchiectasis and summarize the surgical treatment experience of VATS in children with bronchiectasis. DESIGN: Retrospective single-center cohort study. METHODS: A retrospective analysis was conducted on the clinical data of 46 pediatric patients who underwent surgery with bronchiectasis at the Children's Hospital of Chongqing Medical University from May 2015 to May 2023. The patients were divided into two groups: the VATS group (25 cases) and the thoracotomy group (21 cases). Comparative analysis was performed on various parameters including basic clinical data, surgical methods, operation time, intraoperative blood loss, transfusion status, postoperative pain, postoperative mechanical ventilation time, chest tube drainage time, length of hospital stay, incidence of complications, and follow-up information. RESULTS: There were no statistically significant differences between the two groups of patients in terms of age, weight, gender, etiology, duration of symptoms, site of onset, and comorbidities (p > 0.05). The operation time in the VATS group was longer than that in the thoracotomy group (p < 0.001). However, the VATS group had better outcomes in terms of intraoperative blood loss, transfusion status, postoperative pain, postoperative mechanical ventilation time, chest tube drainage time, and length of hospital stay (p < 0.05). The incidence of postoperative complications in the VATS group was lower than that in the thoracotomy group, although the difference was not statistically significant (p = 0.152). Follow-up data showed no statistically significant difference in the surgical treatment outcomes between the two groups (p = 0.493). CONCLUSION: The incidence of complications and mortality in surgical treatment of bronchiectasis is acceptable. Compared with thoracotomy surgery, VATS has advantages such as smaller trauma, less pain, faster recovery, and fewer complications. For suitable pediatric patients with bronchiectasis, VATS is a safe and effective surgical method.


Assuntos
Bronquiectasia , Cirurgia Torácica Vídeoassistida , Humanos , Criança , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos Retrospectivos , Estudos de Coortes , Perda Sanguínea Cirúrgica , Bronquiectasia/cirurgia , Dor Pós-Operatória/etiologia , Tempo de Internação , Fibrose
20.
Zookeys ; 1190: 303-317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333669

RESUMO

The few already published generic features of the genus Prochasma Warren, 1897 are reviewed and new-found characters are added to make the generic description more comprehensive. A new species, Prochasmadiaoluoensis Liu & Stüning, sp. nov. is described from Hainan Province, China. It is the only Prochasma species found on this island and exceptional for its conspicuous pattern, vivid coloration and some morphological characters not observed in other species before. Descriptions and illustrations of adults, their venation, and male and female genitalia are presented. An identification key and an annotated checklist of all presently known species of Prochasma are provided. In addition, a DNA barcode sequence is given for the new species, and preliminary phylogenetic estimations of the genus Prochasma are discussed.

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