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1.
Artigo em Inglês | MEDLINE | ID: mdl-38763304

RESUMO

OBJECTIVE: Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remains clinically challenging. In this study, we investigate the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase II trial. METHODS: Blood samples were prospectively collected from 45 stage IIIA (N2) NSCLC patients undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the CT-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. RESULTS: At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 Muts/Mb was associated with significantly higher MPR rates (77.8% vs. 38.5%, p = 0.042), and longer disease-free survival (DFS, p = 0.043), but not overall survival (p = 0.131), compared to bTMB < 11 Muts/Mb in 35 patients with bTMB available. The developed DL model achieved an area under the curve (AUC) of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an AUC of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathological response and survival. Compared to ctDNA residual, ctDNA clearance before surgery was associated with significantly higher MPR rates (88.2% vs. 11.1%, p < 0.001) and improved DFS (p = 0.010). CONCLUSIONS: The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

2.
Heliyon ; 10(9): e30668, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38774097

RESUMO

Objective: To analyse and continually improve existing issues in the quality improvement process of medical linear accelerators (LINACs) and enhance the quality control management of LINACs. Methods: Data were collected from eight LINACs (sourced from three manufacturers) at Zhejiang Cancer Hospital using Excel diaries between January 2019 and December 2020. The data description and analysis were performed using the analytic hierarchy process, SPSSAU and Excel software, and mean-time-to-repair (MTTR)/mean-time-between-failure (MTBF) metrics. Continuous quality improvement was executed using the quality control circle (QCC) quality management method. Results: After quality improvement, the risk frequency of 'LINAC down' events decreased by 43.63% and downtime was reduced by 40.45%. The weight of downtime risk improved by 73.69%. The MTTR recovery value increased by 31.90%, and MTBF reliability increased by 2.97 h. The simulation results demonstrated that the proposed quality improvement measures could effectively decrease the frequency and duration of downtimes, consequently extending the normal operational time of LINACs. Conclusion: Transitioning from instant repair to preventative maintenance can enhance the operational efficiency of equipment and yield economic benefits for hospitals. The QCC method and the event risk evaluation model are effective in reducing the downtime of LINACs and improving their quality control management.

3.
Front Immunol ; 15: 1381061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774877

RESUMO

Background: Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs. Methods: We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model. Results: A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence. Conclusions: Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.


Assuntos
Neoplasias Gastrointestinais , Inibidores de Checkpoint Imunológico , Estadiamento de Neoplasias , Humanos , Feminino , Masculino , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Adulto , Glândula Tireoide/patologia , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Prognóstico , Biomarcadores Tumorais
4.
Front Neurosci ; 18: 1357435, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745934

RESUMO

Background: A few studies are emerging to explore the issue of how aging promotes emotional response inhibition. However, there is a lack of empirical study concerning the impact of pathological cognitive impairment on emotional response inhibition. The present study investigated the effect of emotion on response inhibition in people with mild cognitive impairment, the stage of cognitive impairment before dementia. Methods: We used two emotional stop-signal tasks to explore whether the dual competition framework considering limited cognitive resources could explain the relationship between emotion and response inhibition in mild cognitive impairment. Results: The results showed that negative emotions prolonged N2 latency. The Go trial accuracy was reduced in the high-arousal negative conditions and the stop-signal reaction time was prolonged under high-arousal conditions. This study also verified impaired response inhibition in mild cognitive impairment and found that negative emotions prolonged P3 latency in mild cognitive impairment. Conclusion: Emotional information interferes with response inhibition in mild cognitive impairment populations, possibly because emotional information captures more attentional resources, thus interfering with response inhibition that relies on common-pool resources.

5.
Cancer Lett ; 593: 216951, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38734159

RESUMO

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK + effector memory T cells (Tem) were relatively enriched and CXCL13+ exhausted T cells (Tex) and regulator T cells (Treg) decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B + memory B cells (Bmem) suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK + Tem and TNFRSF13B + Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

6.
Water Res ; 257: 121683, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703542

RESUMO

Efficient uranium capture from wastewater holds great importance for the environmental remediation and sustainable development of nuclear energy, but it is a tremendous challenge. Herein, a facile and scalable approach is reported to fabricate functionalized hierarchical porous polymers (PPN-3) decorated with high density of phosphate groups for uranium adsorption. The as-constructed hierarchical porous structure could allow rapid diffusion of uranyl ions, while abundant phosphate groups that serve as adsorption sites could provide the high affinity for uranyl. Consequently, PPN-3 shows a high uranium adsorption uptake of 923.06 mg g-1 and reaches adsorption equilibrium within simply 10 min in uranium-spiked aqueous solution. Moreover, PPN-3 affords selective adsorption of uranyl over multiple metal ions and possesses a rapid and high removal rate of U(VI) in real water systems. Furthermore, this study offers direct polymerization strategy for the cost-effective fabrication of phosphate-functionalized porous organic polymers, which may provide promising application potential for uranium extraction.


Assuntos
Polímeros , Urânio , Urânio/química , Adsorção , Polímeros/química , Porosidade , Purificação da Água/métodos , Poluentes Radioativos da Água
7.
Microorganisms ; 12(5)2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38792853

RESUMO

The Enterobacter cancerogenus strain EcHa1 was isolated from the dead larvae of Helicoverpa armigera, and has the potential for biocontrol of some Lepidoptera insects. In order to screen insecticidal-related genes by qRT-PCR, stable endogenous reference genes used for normalizing qRT-PCR data were selected and evaluated from 13 housekeeping genes (HKGs). The expression levels of the HKGs were determined using qRT-PCR under different experimental conditions, including two culture temperatures and three bacterial OD values. Five stability analysis methods (Ct, BestKeeper, NormFinder, geNorm, and RefFinder) were used to comprehensively rank the candidate genes. The results showed that the optimal reference genes varied under different experimental conditions. The combination of gyrA and gyrB was recommended as the best reference gene combination at 28 °C, while gyrA and rpoB was the best combination at 37 °C. When the OD values were 0.5, 1.0 and 2.0, the recommended reference gene combinations were ftsZ and gyrA, rpoB and gyrB, and gyrA and pyk, respectively. The most suitable reference genes were gyrA and gyrB under all experimental conditions. Using gyrA and gyrB as the reference genes for qRT-PCR, EcHa1 was found to invade all tissues of the H. armigera larvae, and expressed a candidate pathogenic factor Hcp at high levels in gut, Malpighian tubules, and epidermis tissues. This study not only establishes an accurate and reliable normalization for qRT-PCR in entomopathogenic bacteria but also lays a solid foundation for further study of functional genes in E. cancerogenus.

8.
Adv Healthc Mater ; : e2401160, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757919

RESUMO

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

9.
Nat Neurosci ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741020

RESUMO

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

10.
J Am Chem Soc ; 146(20): 14278-14286, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38727720

RESUMO

The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp3)-C(sp3) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.

11.
Sci Total Environ ; 931: 172926, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38697519

RESUMO

Flash droughts characterized by rapid onset and intensification are expected to be a new normal under climate change and potentially affect vegetation photosynthesis and terrestrial carbon sink. However, the effects of flash drought on vegetation photosynthesis and their potential dominant driving factors remain uncertain. Here, we quantify the susceptibility and response magnitude of vegetation photosynthesis to flash drought across different ecosystems (i.e., forest, shrubland, grassland, and cropland) in China based on reanalysis and satellite observations. By employing the extreme gradient boosting model, we also identify the dominant factors that influence these flash drought-photosynthesis relationships. We show that over 51.46 % of ecosystems across China are susceptible to flash drought, and grasslands are substantially suppressed, as reflected in both sensitivity and response magnitude (with median gross primary productivity anomalies of -0.13). We further demonstrate that background climate differences (e.g., mean annual temperature and aridity) predominantly regulate the response variation in forest and shrubland, with hotter/colder or drier ecosystems being more severely suppressed by flash drought. However, in grasslands and croplands, the differential vegetation responses are attributed to the intensity of abnormal hydro-meteorological conditions during flash drought (e.g., vapor pressure deficit (VPD) and temperature anomalies). The effects of flash droughts intensify with increasing VPD and nonmonotonically relate to temperature, with colder or hotter temperatures leading to more severe vegetation loss. Our results identify the vulnerable ecological regions under flash drought and enable a better understanding of vegetation photosynthesis response to climate extremes, which may be useful for developing effective management strategies.


Assuntos
Mudança Climática , Secas , Ecossistema , Fotossíntese , China , Florestas
12.
J Hazard Mater ; 473: 134595, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38761769

RESUMO

A biocatalytic system comprising fungal laccase and mediators can generate phenol radicals and efficiently eliminate various triarylmethane dyes. This study systematically explores the kinetic impact of dissolved organic matter (DOM), represented by humic substance (HS consisting of 90% fulvic acid, from lignite), on the decolorization of seven typical triarylmethane dyes by Trametes versicolor laccase and twenty natural mediators. Among these, 4-hydroxybenzyl alcohol (4-HA) and methyl violet (MV) undergo in-depth investigation regarding degradation products, pathways, and reaction mechanisms. In instances where HS hampers laccase-alone decolorization, such as malachite green, Coomassie brilliant blue, bromophenol blue, and acid magenta, this inhibition may persist despite mediator introduction. Conversely, in cases where HS facilitates decolorization, such as crystalline violet and ethyl violet, most laccase-mediator systems (LMSs) can still benefit. For MV decolorization by laccase and 4-HA, HS's kinetic effect is controlled by concentration and reaction time. A 5 mg/L HS increased the decolorization rate from 50% to 67% within the first hour, whereas 10 mg/L HS only achieved 45%. After 16 h of reaction, HS's impact on decolorization rate diminishes. Furthermore, the addition of HS enhances precipitation production, probably due to its involvement in polymerization with MV and mediator. Computational simulations and spectral monitoring reveal that low HS concentrations accelerate laccase-mediated demethylation by disrupting the chromophores bound to MV, thus promoting the decolorization of MV. Conversely, inhibition by high HS concentrations stems from the competitive binding of the enzyme pocket to the mediator, and the reduction of phenol free radicals in the system. Molecular docking and kinetic simulations revealed that laccase forms complexes with both the mediator and MV. Interestingly, the decolorization of MV occurred through a non-radical mechanism in the presence of HS. This work provided a reference for screening of high catalytic performance mediators to remove triarylmethane dyes in the actual water environment.

13.
Materials (Basel) ; 17(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38793256

RESUMO

The experimental and numerical simulation analysis of a TiAl alloy by laser metal deposition technology is presented in this paper. The research examines the macroscopic morphology, microstructure, and mechanical properties of samples as laser power varies. It also delves into how the temperature field and residual stress evolve under different laser powers. The results reveal that the microstructure of samples is mainly composed of α2-Ti3Al phase and a γ-TiAl phase and that the details of the microstructure are significantly affected by laser power. As laser power increases, coarse lamellar structure content increases, corresponding to a decrease in α2 phase content. The deposited layer hardness ranges from 550 HV to 600 HV, and the average deposition layer hardness decreases with increased laser power. Simulation results predict the molten pool's size, temperature, and residual stresses. A significant increase in the molten pool size is observed when the laser power exceeds 1000 W, and the measured molten pool depths correspond closely to simulation predictions. However, significant tensile stresses are generated in the deposition layer due to high cooling rates, mainly in the x direction. Cracks are observed on the surface of the deposition layer at all laser powers.

14.
J Pharm Anal ; 14(5): 100929, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799234

RESUMO

Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.

15.
Bioresour Technol ; : 130904, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38801957

RESUMO

Chlamydomonas reinhardtii prefers ammonium (NH4+) as a nitrogen source, but its late-stage growth under high-NH4+ concentrations (0.5 ∼ 1 g/L) is retarded due to medium acidification. In this study, oyster shell powders were shown to increase the tolerance of C. reinhardtii to NH4+ supplementation at 0.7 g/L in TAP medium in 1-L bubble-column bioreactors, resulting in a 22.9 % increase in biomass production, 62.1 % rise in unsaturated fatty acid accumulation, and 19.2 % improvement in harvesting efficiency. Powdered oyster shell mitigated medium acidification (pH 7.2-7.8) and provided dissolved inorganic carbon up to 8.02 × 103 µmol/L, facilitating a 76.3 % NH4+ consumption, release of up to 189 mg/L of Ca2+, a 42.1 % reduction in ζ-potential and 27.7 % increase in flocculation activity of microalgae cells. This study highlights a promising approach to utilize powdered oyster shell as a liming agent, supplement carbon source, and bio-flocculant for enhancing biomass production and microalgae harvesting in NH4+-rich environments.

16.
J Ovarian Res ; 17(1): 108, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762521

RESUMO

BACKGROUND: Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR). METHODS: A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions. RESULTS: The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67-4.43)], Li [OR: 1.89 (1.06-3.42)], and Cs [OR: 1.97 (1.10-3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect. CONCLUSION: This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Líquido Folicular , Reserva Ovariana , Humanos , Feminino , Líquido Folicular/metabolismo , Líquido Folicular/química , Estudos de Casos e Controles , Adulto , Reserva Ovariana/fisiologia , Metais Alcalinoterrosos/análise , Álcalis , Infertilidade Feminina/metabolismo , Adulto Jovem
17.
Front Oncol ; 14: 1391546, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764577

RESUMO

Objectives: The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness. Methods: We systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311). Results: From the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events. Conclusions: Patients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.

18.
Front Vet Sci ; 11: 1376678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764852

RESUMO

Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection.

19.
Med Princ Pract ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772352

RESUMO

Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer globally, poses a substantial health burden. HCC development is influenced by multiple risk factors including hepatitis B and C infections, excessive alcohol consumption, nonalcoholic steatohepatitis (NASH), and demographic variables like gender, race, and age. Although the exact etiology of HCC is not fully understood, HCC formation is a multi-step process that is contributed by the interplays of viral infection, hepatocyte oncogenic mutations, and chronic liver diseases such as alcoholic cirrhosis and NASH. Disease stage significantly impacts HCC prognosis, with 5-year survival rates ranging from 36% in early-stage cases to 13% in late-stage metastatic cases. Therefore, there is significant potential for life-saving and socioeconomic benefits through the implementation of surveillance programs and the introduction of low-cost screening measures for high-risk groups, such as ultrasound imaging and blood tests. Treatment options for HCC encompass surgery, liver transplantation, radiation therapy, chemotherapy, targeted therapy, and immunotherapy. Despite therapeutic advances, the treatment of advanced HCC remains a challenge. The prognosis of advanced HCC could be greatly improved with continued efforts in prevention, early detection, and treatment development. These efforts will ultimately lead to improved patient outcomes and increased chances of long-term survival.

20.
Environ Health Perspect ; 132(5): 57009, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38775486

RESUMO

BACKGROUND: More frequent and intense exposure to extreme heat conditions poses a serious threat to public health. However, evidence on the association between heat and specific diagnoses of morbidity is still limited. We aimed to comprehensively assess the short-term association between cause-specific hospital admissions and high temperature, including the added effect of temperature variability and heat waves and the effect modification by humidity and air pollution. METHODS: We used data on cause-specific hospital admissions, weather (i.e., temperature and relative humidity), and air pollution [i.e., fine particulate matter with aerodynamic diameter ≤2.5µm (PM2.5), fine particulate matter with aerodynamic diameter ≤10µm (PM10), NO2, and ozone (O3)] for 48 provinces in mainland Spain and the Balearic Islands between 1 January 2006 and 31 December 2019. The statistical analysis was performed for the summer season (June-September) and consisted of two steps. We first applied quasi-Poisson generalized linear regression models in combination with distributed lag nonlinear models (DLNM) to estimate province-specific temperature-morbidity associations, which were then pooled through multilevel univariate/multivariate random-effect meta-analysis. RESULTS: High temperature had a generalized impact on cause-specific hospitalizations, while the added effect of temperature variability [i.e., diurnal temperature range (DTR)] and heat waves was limited to a reduced number of diagnoses. The strongest impact of heat was observed for metabolic disorders and obesity [relative risk (RR) = 1.978; 95% empirical confidence interval (eCI): 1.772, 2.208], followed by renal failure (1.777; 95% eCI: 1.629, 1.939), urinary tract infection (1.746; 95% eCI: 1.578, 1.933), sepsis (1.543; 95% eCI: 1.387, 1.718), urolithiasis (1.490; 95% eCI: 1.338, 1.658), and poisoning by drugs and nonmedicinal substances (1.470; 95% eCI: 1.298, 1.665). We also found differences by sex (depending on the diagnosis of hospitalization) and age (very young children and the elderly were more at risk). Humidity played a role in the association of heat with hospitalizations from acute bronchitis and bronchiolitis and diseases of the muscular system and connective tissue, which were higher in dry days. Moreover, heat-related effects were exacerbated on high pollution days for metabolic disorders and obesity (PM2.5) and diabetes (PM10, O3). DISCUSSION: Short-term exposure to heat was found to be associated with new diagnoses (e.g., metabolic diseases and obesity, blood diseases, acute bronchitis and bronchiolitis, muscular and connective tissue diseases, poisoning by drugs and nonmedicinal substances, complications of surgical and medical care, and symptoms, signs, and ill-defined conditions) and previously identified diagnoses of hospital admissions. The characterization of the vulnerability to heat can help improve clinical and public health practices to reduce the health risks posed by a warming planet. https://doi.org/10.1289/EHP13254.


Assuntos
Hospitalização , Temperatura Alta , Espanha/epidemiologia , Humanos , Hospitalização/estatística & dados numéricos , Estudos Transversais , Temperatura Alta/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Poluentes Atmosféricos/análise , Feminino , Masculino
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