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1.
Arch Dermatol Res ; 316(7): 463, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985170

RESUMO

OBJECTIVE: The aim is to evaluate the global, regional, and national trends in the burden of children and adolescents under 14 from 1990 to 2019, as well as future trend predictions. METHODS: In Global Burden of Disease (GBD), we reported the incidence, prevalence rate and the years lived with disability (YLDs), the incidence per 100,000 people, and the average annual percentage change (AAPC). We further analyzed these global trends by age, gender, and social development index (SDI). We use joinpoint regression analysis to determine the year with the largest global trend change. Bayesian age-period-cohort (BAPC) was used for predictions. RESULTS: From 1990 to 2019, the incidence rate, prevalence and YLDs of AD under 14 years old showed a downward trend. The incidence rate of AD among people under 5 years old has the largest decline [AAPC: -0.13 (95% CI: -0.15 to -0.11), P < 0.001]. The incidence rate, prevalence and YLDs of AD in women were higher than those in men regardless of age group. Regional, Asia has the highest AD incidence rate in 2019. National, Mongolia has the highest AD incidence rate in 2019. The largest drop in AD incidence rate, prevalence and YLDs between 1990 and 2019 was in the United States. CONCLUSION: From 1990 to 2019, the global incidence rate of children and adolescents under 14 declined. With the emergence of therapeutic drugs, the prevalence and YLDs rate declined significantly. From 2020 to 2030, there is still a downward trend.


Assuntos
Dermatite Atópica , Carga Global da Doença , Humanos , Dermatite Atópica/epidemiologia , Adolescente , Carga Global da Doença/tendências , Masculino , Feminino , Criança , Pré-Escolar , Lactente , Incidência , Prevalência , Saúde Global/estatística & dados numéricos , Recém-Nascido , Teorema de Bayes , Previsões , Anos de Vida Ajustados por Deficiência/tendências
2.
Microsyst Nanoeng ; 10: 98, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015941

RESUMO

Flexible sensors are essential components in emerging fields such as epidermal electronics, biomedicine, and human-computer interactions, and creating high-performance sensors through simple structural design for practical applications is increasingly needed. Presently, challenges still exist in establishing efficient models of flexible piezoresistive pressure sensors to predict the design required for achieving target performance. This work establishes a theoretical model of a flexible pressure sensor with a simple laminated and enclosed structure. In the modeling, the electrical constriction effect is innovatively introduced to explain the sensitization mechanism of the laminated structure to a broad range of pressures and to predict the sensor performance. The experimental results confirmed the effectiveness of the theoretical model. The sensor exhibited excellent stability for up to three million cycles and superior durability when exposed to salt solution owing to its simple laminated and enclosed structural design. Finally, a wearable sensing system for real-time collection and analysis of plantar pressure is constructed for exercise and rehabilitation monitoring applications. This work aims to provide theoretical guidance for the rapid design and construction of flexible pressure sensors with target performance for practical applications.

3.
Biomed Pharmacother ; 177: 117121, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39002443

RESUMO

OBJECTIVES: Celastrol has widespread therapeutic applications in various pathological conditions, including chronic inflammation. Previous studies have demonstrated the potent cardioprotective effects of celastrol. Nevertheless, limited attention has been given to its potential in reducing ventricular arrhythmias (VAs) following myocardial infarction (MI). Hence, this study aimed to elucidate the potential mechanisms underlying the regulatory effects of celastrol on VAs and cardiac electrophysiological parameters in rats after MI. METHODS: Sprague-Dawley rats were divided at random: the sham, MI, and MI + celastrol groups. The left coronary artery was occluded in the MI and MI + Cel groups. Electrocardiogram, heart rate variability (HRV), ventricular electrophysiological parameters analysis, histology staining of ventricles, Enzyme-linked immunosorbent assay (ELISA), western blotting and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to elucidate the underlying mechanism of celastrol. Besides, H9c2 cells were subjected to hypoxic conditions to create an in vitro model of MI and then treated with celastrol for 24 hours. Nigericin was used to activate the NLRP3 inflammasome. RESULTS: Compared with that MI group, cardiac electrophysiology instability was significantly alleviated in the MI + celastrol group. Additionally, celastrol improved HRV, upregulated the levels of Cx43, Kv.4.2, Kv4.3 and Cav1.2, mitigated myocardial fibrosis, and inhibited the NLRP3 inflammasome pathway. In vitro conditions also supported the regulatory effects of celastrol on the NLRP3 inflammasome pathway. CONCLUSIONS: Celastrol could alleviate the adverse effects of VAs after MI partially by promoting autonomic nerve remodeling, ventricular electrical reconstruction and ion channel remodeling, and alleviating ventricular fibrosis and inflammatory responses partly by through inhibiting the NLRP3/Caspase-1/IL-1ß pathway.

4.
Materials (Basel) ; 17(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38998396

RESUMO

The CoCrFeMnNi high-entropy alloy is commonly used for vascular stents due to its excellent mechanical support and ductility. However, as high-entropy alloy stents can cause inflammation in the blood vessels, leading to their re-narrowing, drug-eluting stents have been developed. These stents have nanopores on their surfaces that can carry drug particles to inhibit inflammation and effectively prevent re-narrowing of the blood vessels. To optimize the mechanical properties and drug-carrying capacity of high-entropy alloy stents, a high-entropy alloy system with different wide and deep square-shaped nanopore distributions is created using molecular dynamics. The mechanical characteristics and dislocation evolution mechanism of different nanopore high-entropy alloy systems under tensile stress were studied. The results showed that the CoCrFeMnNi high-entropy alloy with a rational nanopore distribution can effectively maintain the mechanical support required for a vascular stent. This research provides a new direction for the manufacturing process of nanopores on the surfaces of high-entropy alloy stents.

5.
Front Immunol ; 15: 1408928, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035009

RESUMO

Objective: To determine the cost-effectiveness of imported immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab, and domestic ICIs like serplulimab and adebrelimab, in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) in China. Methods: Using a 21-day cycle length and a 20-year time horizon, a Markov model was established to compare the clinical and economic outcomes of five first-line ICIs plus chemotherapy versus chemotherapy alone, as well as against each other, from the perspective of the Chinese healthcare system. Transition probabilities were estimated by combining the results of the CAPSTONE-1 trial and a published network meta-analysis. Cost and health state utilities were collected from multiple sources. Both cost and effectiveness outcomes were discounted at a rate of 5% annually. The primary model output was incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were preformed to assess the robustness of the model. Results: In the base-case analysis, the addition of first-line ICIs to chemotherapy resulted in the ICERs ranged from $80,425.31/QALY to $812,415.46/QALY, which exceeded the willing-to-pay threshold set for the model. When comparing these first-line immunochemotherapy strategies, serplulimab plus chemotherapy had the highest QALYs of 1.51286 and the second lowest costs of $60,519.52, making it is the most cost-effective strategy. Our subgroup-level analysis yielded results that are consistent with the base-case analysis. The sensitivity analysis results confirmed the validity and reliability of the model. Conclusion: In China, the combination of fist-line ICIs plus chemotherapy were not considered cost-effective when compared to chemotherapy alone. However, when these fist-line immunochemotherapy strategies were compared with each other, first-line serplulimab plus chemotherapy consistently demonstrated superiority in terms of cost-effectiveness. Reducing the cost of serplulimab per 4.5 mg/kg would be a realistic step towards making first-line serplulimab plus chemotherapy more accessible and cost-effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Análise Custo-Benefício , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/economia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/economia , China , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anos de Vida Ajustados por Qualidade de Vida , Estadiamento de Neoplasias , Cadeias de Markov , Análise de Custo-Efetividade
6.
Ecol Evol ; 14(7): e11677, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38962021

RESUMO

The hemiparasitic tribe Cymbarieae (Orobanchaceae) plays a crucial role in elucidating the initial stage of the transition from autotrophism to heterotrophism. However, the complete chloroplast genome of the type genus Cymbaria has yet to be reported. In addition, the traditional Mongolian medicine Cymbaria daurica is frequently subjected to adulteration or substitution because of the minor morphological differences with Cymbaria mongolica. In this study, the complete chloroplast genomes of the two Cymbaria species were assembled and annotated, and those of other published 52 Orobanchaceae species were retrieved for comparative analyses. We found that the Cymbaria chloroplast genomes are characterized by pseudogenization or loss of stress-relevant genes (ndh) and a unique rbcL-matK inversion. Unlike the high variability observed in holoparasites, Cymbaria and other hemiparasites exhibit high similarity to autotrophs in genome size, guanine-cytosine (GC) content, and intact genes. Notably, four pairs of specific DNA barcodes were developed and validated to distinguish the medicinal herb from its adulterants. Phylogenetic analyses revealed that the genus Cymbaria and the Schwalbea-Siphonostegia clade are grouped into the tribe Cymbarieae, which forms a sister clade to the remaining Orobanchaceae parasitic lineages. Moreover, the diversification of monophyletic Cymbaria occurred during the late Miocene (6.72 Mya) in the Mongol-Chinese steppe region. Our findings provide valuable genetic resources for studying the phylogeny of Orobanchaceae and plant parasitism, and genetic tools to validate the authenticity of the traditional Mongolian medicine "Xinba.".

7.
Heliyon ; 10(12): e32588, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39021903

RESUMO

Understanding influential factors for the academic performance of doctoral students is crucial for supporting their exploration of academic research opportunities and aiding their pursuit of careers in academic research. This study surveyed 659 doctoral students in China, utilizing scales to assess academic motivation, buoyancy, self-efficacy, self-concept, and performance. Based on a partial least squares structural equation modeling (PLS-SEM) analysis, a direct correlation between self-concept and performance was identified. Moreover, motivation, buoyancy, and self-efficacy were significant mediators in the relationship between self-concept and performance. To significantly enhance self-concept's impact on doctoral students' academic performance, educators should endeavor to enhance students' motivation, buoyancy, and self-efficacy. This endeavor will contribute to the discourse on academic performance and its underlying psychological mechanisms.

8.
Adv Sci (Weinh) ; : e2307804, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837887

RESUMO

RNA splicing is crucial in the multilayer regulatory networks for gene expression, making functional interactions with DNA- and other RNA-processing machineries in the nucleus. However, these established couplings are all major spliceosome-related; whether the minor spliceosome is involved remains unclear. Here, through affinity purification using Drosophila lysates, an interaction is identified between the minor spliceosomal 65K/RNPC3 and ANKRD11, a cofactor of histone deacetylase 3 (HDAC3). Using a CRISPR/Cas9 system, Deletion strains are constructed and found that both Dm65KΔ/Δ and Dmankrd11Δ/Δ mutants have reduced histone deacetylation at Lys9 of histone H3 (H3K9) and Lys5 of histone H4 (H4K5) in their heads, exhibiting various neural-related defects. The 65K-ANKRD11 interaction is also conserved in human cells, and the HsANKRD11 middle-uncharacterized domain mediates Hs65K association with HDAC3. Cleavage under targets and tagmentation (CUT&Tag) assays revealed that HsANKRD11 is a bridging factor, which facilitates the synergistic common chromatin-binding of HDAC3 and Hs65K. Knockdown (KD) of HsANKRD11 simultaneously decreased their common binding, resulting in reduced deacetylation of nearby H3K9. Ultimately, this study demonstrates that expression changes of many genes caused by HsANKRD11-KD are due to the decreased common chromatin-binding of HDAC3 and Hs65K and subsequently reduced deacetylation of H3K9, illustrating a novel and conserved coupling mechanism that links the histone deacetylation with minor spliceosome for the regulation of gene expression.

9.
BMC Anesthesiol ; 24(1): 212, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918712

RESUMO

BACKGROUND: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women. METHODS: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level. RESULTS: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed. CONCLUSIONS: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period. CLINICAL TRIAL NUMBER AND REGISTRY URL: The registration number: ChiCTR2200065201; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 31/10/2022.


Assuntos
Analgesia Obstétrica , Anestésicos Locais , Cesárea , Procaína , Ropivacaina , Humanos , Feminino , Ropivacaina/administração & dosagem , Gravidez , Método Duplo-Cego , Cesárea/métodos , Anestésicos Locais/administração & dosagem , Adulto , Analgesia Obstétrica/métodos , Procaína/análogos & derivados , Procaína/administração & dosagem
10.
Cancer Gene Ther ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877164

RESUMO

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

11.
Adv Sci (Weinh) ; : e2402497, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884340

RESUMO

Catalysis is crucial to improve redox kinetics in lithium-sulfur (Li-S) batteries. However, conventional catalysts that consist of a single metal element are incapable of accelerating stepwise sulfur redox reactions which involve 16-electron transfer and multiple Li2Sn (n = 2-8) intermediate species. To enable fast kinetics of Li-S batteries, it is proposed to use high-entropy alloy (HEA) nanocatalysts, which are demonstrated effective to adsorb lithium polysulfides and accelerate their redox kinetics. The incorporation of multiple elements (Co, Ni, Fe, Pd, and V) within HEAs greatly enhances the catalytically active sites, which not only improves the rate capability, but also elevates the cycling stability of the assembled batteries. Consequently, HEA-catalyzed Li-S batteries achieve a high capacity up to 1364 mAh g-1 at 0.1 C and experience only a slight capacity fading rate of 0.054% per cycle over 1000 cycles at 2 C, while the assembled pouch cell achieves a high specific capacity of 1192 mAh g-1. The superior performance of Li-S batteries demonstrates the effectiveness of the HEA catalysts with maximized synergistic effect for accelerating S conversion reactions, which opens a way to catalytically improving stepwise electrochemical conversion reactions.

12.
Polymers (Basel) ; 16(12)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38931984

RESUMO

Biofouling is a great challenge for engineering material in medical-, marine-, and pharmaceutical-related applications. In this study, a novel trimethylamine N-oxide (TMAO)-analog monomer, 3-(2-methylacrylamido)-N,N-dimethylpropylamine N-oxide (MADMPAO), was synthesized and applied for the grafting of poly(MADMPAO) (pMPAO) brushes on quartz crystal microbalance (QCM) chips by the combination of bio-inspired poly-dopamine (pDA) and surface-initiated atom transfer radical polymerization technology. The result of ion adsorption exhibited that a sequential pDA and pMPAO arrangement from the chip surface had different characteristics from a simple pDA layer. Ion adsorption on pMPAO-grafted chips was greatly inhibited at low salt concentrations of 1 and 10 mmol/L due to strong surface hydration in the presence of charged N+ and O- of zwitterionic pMPAO brushes on the outer layer on the chip surface, well known as the "anti-polyelectrolyte" effect. During BSA adsorption, pMPAO grafting also led to a marked decrease in frequency shift, indicating great inhibition of protein adsorption. It was attributed to weaker BSA-pMPAO interaction. In this study, the Au@pDA-4-pMPAO chip with the highest coating concentration of DA kept stable dissipation in BSA adsorption, signifying that the chip had a good antifouling property. The research provided a novel monomer for zwitterionic polymer and demonstrated the potential of pMPAO brushes in the development and modification of antifouling materials.

13.
BMC Musculoskelet Disord ; 25(1): 484, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38898448

RESUMO

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.


Assuntos
Fixação Interna de Fraturas , Vértebras Lombares , Procedimentos Cirúrgicos Robóticos , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Vértebras Torácicas , Humanos , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Masculino , Pessoa de Meia-Idade , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Espondilite Anquilosante/cirurgia , Espondilite Anquilosante/complicações , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Lombares/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Resultado do Tratamento , Idoso , Duração da Cirurgia , Tempo de Internação , Parafusos Pediculares , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Seguimentos
14.
Adv Ther ; 41(8): 3159-3172, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38888881

RESUMO

INTRODUCTION: This study sought to investigate the affordable price of sotorasib among patients with previously treated advanced KRASG12C-mutant non-small cell lung cancer (NSCLC) through a cost-effectiveness analysis from the perspectives of both the Chinese healthcare system and the patients. METHODS: We developed a Markov model spanning a 20-year time horizon with a cycle length of 21 days. Our data were derived from the CodeBreaK 200 clinical trial, supplemented with published literature, publicly available national databases, and local hospitals. The primary outcomes were the affordable prices of sotorasib which would result in the incremental cost-effectiveness ratios (ICERs) of sotorasib relative to docetaxel below the preset willing-to-pay (WTP) threshold. Sensitivity analyses were performed to evaluate the model's robustness. RESULTS: At the national level, from the perspective of the Chinese healthcare system and patients, the price of sotorasib should be lower than US$0.04673 and $0.03231, respectively, to make it affordable, which is equivalent to $1346 and $931 per box (120 mg × 240 pieces). At the provincial level, the price ceiling of sotorasib/mg fluctuated between $0.04084 to $0.08061 from the Chinese healthcare system's perspective and between $0.02642 to $0.06620 from the patients' perspective. Probabilistic sensitivity analyses revealed that, as the price of sotorasib decreased, its likelihood of being cost-effective increased. CONCLUSION: Sotorasib might be a cost-effective therapy in China. The pharmaco-economic evidence generated from this study has significant implications not only for guiding the drug pricing of the upcoming sotorasib but also for determining the reimbursement ratio for its potential inclusion in the National Reimbursement Drugs List in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Análise Custo-Benefício , Docetaxel , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Docetaxel/uso terapêutico , Docetaxel/economia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/genética , China , Proteínas Proto-Oncogênicas p21(ras)/genética , Antineoplásicos/uso terapêutico , Antineoplásicos/economia , Custos de Medicamentos/estatística & dados numéricos , Cadeias de Markov , Pirimidinas/uso terapêutico , Pirimidinas/economia , Masculino , Piridinas/uso terapêutico , Piridinas/economia , Análise de Custo-Efetividade , Piperazinas
15.
Pharmacol Res ; 205: 107263, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38876442

RESUMO

Pressure overload-induced pathological cardiac hypertrophy eventually leads to heart failure (HF). Unfortunately, lack of effective targeted therapies for HF remains a challenge in clinical management. Mixed-lineage leukemia 4 (MLL4) is a member of the SET family of histone methyltransferase enzymes, which possesses histone H3 lysine 4 (H3K4)-specific methyltransferase activity. However, whether and how MLL4 regulates cardiac function is not reported in adult HF. Here we report that MLL4 is required for endoplasmic reticulum (ER) stress homeostasis of cardiomyocytes and protective against pressure overload-induced cardiac hypertrophy and HF. We observed that MLL4 is increased in the heart tissue of HF mouse model and HF patients. The cardiomyocyte-specific deletion of Mll4 (Mll4-cKO) in mice leads to aggravated ER stress and cardiac dysfunction following pressure overloading. MLL4 knockdown neonatal rat cardiomyocytes (NRCMs) also display accelerated decompensated ER stress and hypertrophy induced by phenylephrine (PE). The combined analysis of Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) data reveals that, silencing of Mll4 alters the chromatin landscape for H3K4me1 modification and gene expression patterns in NRCMs. Interestingly, the deficiency of MLL4 results in a marked reduction of H3K4me1 and H3K27ac occupations on Thrombospondin-4 (Thbs4) gene loci, as well as Thbs4 gene expression. Mechanistically, MLL4 acts as a transcriptional activator of Thbs4 through mono-methylation of H3K4 and further regulates THBS4-dependent ER stress response, ultimately plays a role in HF. Our study indicates that pharmacologically targeting MLL4 and ER stress might be a valid therapeutic approach to protect against cardiac hypertrophy and HF.


Assuntos
Estresse do Retículo Endoplasmático , Insuficiência Cardíaca , Histona-Lisina N-Metiltransferase , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Animais , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/etiologia , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Humanos , Camundongos Knockout , Ratos , Camundongos , Células Cultivadas , Cardiomegalia/metabolismo , Cardiomegalia/genética , Ratos Sprague-Dawley , Trombospondinas
16.
Int J Cardiol ; 411: 132265, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38880416

RESUMO

BACKGROUND: The prognostic efficacy of a coronary computed tomography angiography (CCTA)-derived myocardial radiomics model in patients with chronic myocardial infarction (MI) is unclear. METHODS: In this retrospective study, a cohort of 236 patients with chronic MI who underwent both CCTA and cardiac magnetic resonance (CMR) examinations within 30 days were enrolled and randomly divided into training and testing datasets at a ratio of 7:3. The clinical endpoints were major adverse cardiovascular events (MACE), defined as all-cause death, myocardial reinfarction and heart failure hospitalization. The entire three-dimensional left ventricular myocardium on CCTA images was segmented as the volume of interest for the extraction of radiomics features. Five models, namely the clinical model, CMR model, clinical+CMR model, CCTA-radiomics model, and clinical+CCTA-radiomics model, were constructed using multivariate Cox regression. The prognostic performances of these models were evaluated through receiver operating characteristic curve analysis and the index of concordance (C-index). RESULTS: Fifty-one (20.16%) patients experienced MACE during a median follow-up of 1439.5 days. The predictive performance of the CCTA-radiomics model surpassed that of the clinical model, CMR model, and clinical+CMR model in both the training (area under the curve (AUC) of 0.904 vs. 0.691, 0.764, 0.785; C-index of 0.88 vs. 0.71, 0.75, 0.76, all p values <0.001) and testing (AUC of 0.893 vs. 0.704, 0.851, 0.888; C-index of 0.86 vs. 0.73, 0.85, 0.85, all p values <0.05) datasets. CONCLUSIONS: The CCTA-based myocardial radiomics model is a valuable tool for predicting adverse outcomes in chronic MI, providing incremental value to conventional clinical and CMR parameters.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Infarto do Miocárdio , Valor Preditivo dos Testes , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Retrospectivos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Idoso , Doença Crônica , Imagem Cinética por Ressonância Magnética/métodos , Seguimentos , Prognóstico , Estudos de Coortes , Radiômica
17.
J Phys Chem Lett ; 15(25): 6598-6604, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38885459

RESUMO

Despite the impressive specific capacity of Li-O2 batteries, challenges persist, particularly with lithium metal anode (LMA). These include dendritic growth and unstable solid electrolyte interface (SEI) layers, which become more pronounced in an oxygen-rich environment, a typical operation scenario for Li-O2 batteries. Herein, utilizing a hybrid dual anion electrolyte (DAE) strategy, which incorporates both inorganic LiNO3 and organic Li[(FSO2)(C2F5SO2)N] (LiFPFSI) salts, the dendritic growth is evidently inhibited by creating a "concrete-like" SEI structure. Simultaneously, it fosters the development of a fluorine-rich SEI layer. Consequently, a robust, compact, and stable barrier is formed, adeptly suppressing side reactions between LMA and the electrolyte, particularly those relevant to dissolved O2. The practicality and efficiency of this DAE strategy are validated across a variety of battery types including Li/Li, Li/Cu, and notably Li-O2 batteries, which showcased significantly improved reversibility and durability. These results underscore the important role of multifunctional salts in interphase engineering for LMA, which could lead to advancements in Li-O2 batteries.

18.
Acad Radiol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38777719

RESUMO

RATIONALE AND OBJECTIVES: Diagnosing subcentimeter solid pulmonary nodules (SSPNs) remains challenging in clinical practice. Deep learning may perform better than conventional methods in differentiating benign and malignant pulmonary nodules. This study aimed to develop and validate a model for differentiating malignant and benign SSPNs using CT images. MATERIALS AND METHODS: This retrospective study included consecutive patients with SSPNs detected between January 2015 and October 2021 as an internal dataset. Malignancy was confirmed pathologically; benignity was confirmed pathologically or via follow-up evaluations. The SSPNs were segmented manually. A self-supervision pre-training-based fine-grained network was developed for predicting SSPN malignancy. The pre-trained model was established using data from the National Lung Screening Trial, Lung Nodule Analysis 2016, and a database of 5478 pulmonary nodules from the previous study, with subsequent fine-tuning using the internal dataset. The model's efficacy was investigated using an external cohort from another center, and its accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined. RESULTS: Overall, 1276 patients (mean age, 56 ± 10 years; 497 males) with 1389 SSPNs (mean diameter, 7.5 ± 2.0 mm; 625 benign) were enrolled. The internal dataset was specifically enriched for malignancy. The model's performance in the internal testing set (316 SSPNs) was: AUC, 0.964 (95% confidence interval (95%CI): 0.942-0.986); accuracy, 0.934; sensitivity, 0.965; and specificity, 0.908. The model's performance in the external test set (202 SSPNs) was: AUC, 0.945 (95% CI: 0.910-0.979); accuracy, 0.911; sensitivity, 0.977; and specificity, 0.860. CONCLUSION: This deep learning model was robust and exhibited good performance in predicting the malignancy of SSPNs, which could help optimize patient management.

19.
Int Urogynecol J ; 35(6): 1163-1170, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38695902

RESUMO

INTRODUCTION AND HYPOTHESIS: The potential predictors of pelvic floor reconstruction surgery hypothermia remain unclear. This prospective cohort study was aimed at identifying these predictors and evaluating the outcomes associated with perioperative hypothermia. METHODS: Elderly patients undergoing pelvic floor reconstruction surgery were consecutively enrolled from April 2023 to September 2023. Perioperative temperature was measured at preoperative (T1), every 15 min after the start of anesthesia (T2), and 15 min postoperative (T3) using a temperature probe. Perioperative hypothermia was defined as a core temperature below 36°C at any point during the procedure. Multivariate logistic regression analysis was conducted to determine factors associated with perioperative hypothermia. RESULTS: A total of 229 patients were included in the study, with 50.7% experiencing hypothermia. Multivariate analysis revealed that the surgical method involving pelvic floor combined with laparoscopy, preoperative temperature < 36.5°C, anesthesia duration ≥ 120 min, and the high levels of anxiety were significantly associated with perioperative hypothermia. The predictive value of the multivariate model was 0.767 (95% CI, 0.706 to 0.828). CONCLUSIONS: This observational prospective study identified several predictive factors for perioperative hypothermia in elderly patients during pelvic floor reconstruction surgery. Strategies aimed at preventing perioperative hypothermia should target these factors. Further studies are required to assess the effectiveness of these strategies, specifically in elderly patients undergoing pelvic floor reconstruction surgery.


Assuntos
Hipotermia , Diafragma da Pelve , Humanos , Hipotermia/etiologia , Hipotermia/prevenção & controle , Idoso , Feminino , Estudos Prospectivos , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Período Perioperatório , Fatores de Risco , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Laparoscopia , Prolapso de Órgão Pélvico/cirurgia
20.
J Pediatr Endocrinol Metab ; 37(6): 505-515, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38700489

RESUMO

OBJECTIVES: The aim of this study was to evaluate the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1 , Exercício Físico , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Criança , Insulina/administração & dosagem , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Adolescente , Glicemia/análise , Hipoglicemia/prevenção & controle , Prognóstico
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