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1.
Diagnostics (Basel) ; 14(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893618

RESUMO

Artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopedic-specific problems. One particular area of investigation focuses on shoulder pathology, which is a range of disorders or abnormalities of the shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate current AI applications in shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI technology are also discussed.

2.
Int J Biol Macromol ; : 133266, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906347

RESUMO

As a marine antifouling biocide, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) exhibited high toxicity to marine organisms. This study investigated the interaction between DCOIT and human serum albumin (HSA) using several spectroscopic techniques combined with computer prediction methods. The UV-vis absorption spectra, Stern-Volmer constant (KSV) and fluorescence resonance energy transfer (FRET) results indicated that DCOIT caused static quenching of HSA fluorescence. The ΔG°, ΔH° and ΔS° values were - 31.03 ±â€¯0.17 kJ·mol-1, -133.54 ±â€¯0.88 kJ·mol-1 and - 348.46 ±â€¯2.86 J.mol-1·K-1, respectively, suggesting that van der Waals forces and hydrogen bonds governed the spontaneous formation of the complex. Synchronous fluorescence and circular dichroism (CD) spectroscopy observed the burial of Trp residues within HSA and the unfolding of HSA secondary structure induced by DCOIT. Three-dimensional (3D) fluorescence and Atomic Force Microscopy (AFM) further detected DCOIT-induced loosening of HSA peptide chain structure. Site displacement experiments indicated that DCOIT binding at site I of HSA. Computational predictions indicated that hydrophobic interactions were also essential in the complex. The increased RMSD, Rg, SASA, and RMSF confirmed that DCOIT weakened the stability and compactness of HSA, rendering residues more flexible. Lastly, esterase activity assays demonstrated that DCOIT inhibited esterase activity and interfered with the human detoxification process.

3.
Molecules ; 29(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38930800

RESUMO

Cangjie Temple was built to commemorate Cangjie, the legendary inventor of Chinese characters. It stands as one of the few remaining temples in China dedicated to the invention and creation of writing. In this study, the material properties of wooden paintings from the Cangjie temple were characterized using Polarized Light Microscopy (PLM), Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (SEM-EDS), Micro-confocal Raman Spectroscopy, X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC/MS). It was confirmed that the pigments of the paintings included cinnabar, lapis lazuli, lead white, Paris green, and carbon black. The proteinaceous glue was used as an adhesive in the pigment samples, with tung oil likely being utilized as a primer for the wooden structures before painting. This study not only provides valuable data support for the conservation and restoration of the architectural features of Cangjie Temple but also provides useful reference for the maintenance and inheritance of similar ancient buildings.

4.
Front Oncol ; 14: 1390438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595816

RESUMO

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

5.
Heliyon ; 10(8): e29218, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628758

RESUMO

In recent decades, substantial advancements in epigenetics have unveiled a profound understanding of its mechanisms in tumorigenesis and have offered promising strategies for epigenetic therapy in cancer patients. In our study, through bioinformatics analysis, we discovered a significant downregulation and hypermethylation of FOXI2 in clear cell renal cell carcinoma (ccRCC), while the expression in chromophobe cell carcinoma (chRCC) exhibited the opposite trend. Moreover, we established a strong correlation between FOXI2 expression levels and the prognosis of ccRCC. Gene enrichment analysis and cell function experiments unequivocally demonstrate that FOXI2 possesses the capability to induce cell cycle arrest and inhibit cell proliferation. Our research findings demonstrate that the expression of FOXI2 in ccRCC is under the regulation of promoter hypermethylation. Furthermore, in vitro experiments have conclusively shown that the overexpression of FOXI2 induces cell cycle arrest and inhibits cell proliferation.

6.
Front Pharmacol ; 15: 1308733, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434710

RESUMO

Acute kidney injury (AKI) is a global health problem, given its substantial morbidity and mortality rates. A better understanding of the mechanisms and factors contributing to AKI has the potential to guide interventions aimed at mitigating the risk of AKI and its subsequent unfavorable outcomes. Endoplasmic reticulum stress (ERS) is an intrinsic protective mechanism against external stressors. ERS occurs when the endoplasmic reticulum (ER) cannot deal with accumulated misfolded proteins completely. Excess ERS can eventually cause pathological reactions, triggering various programmed cell death (autophagy, ferroptosis, apoptosis, pyroptosis). This article provides an overview of the latest research progress in deciphering the interaction between ERS and different programmed cell death. Additionally, the report consolidates insights into the roles of ERS in AKI and highlights the potential avenues for targeting ERS as a treatment direction toward for AKI.

7.
Opt Express ; 32(4): 5273-5286, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439259

RESUMO

We investigate theoretically the photoelectron momentum distributions (PMDs) of the helium atom in the few-cycle nonlinear chirped laser pulse. The numerical results show that the direction of the spider-like interference structure in PMDs exhibits periodic variations with the increase of the chirp parameter. It is illustrated that the direction of the spider-like interference structure is related to the direction of the electron motion by tracking the trajectories of the electrons. We also demonstrate that the carrier-envelope phase can precisely control the opening of the ionization channel. In addition, we investigate the PMDs when a chirp-free second harmonic (SH) laser pulse is added to the chirped laser field, the numerical results show that the interference patterns can change from only spider-like interference structure to both spider-like and ring-like interference structures.

8.
Opt Lett ; 49(6): 1425-1428, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489416

RESUMO

Terahertz cross correlation spectroscopy (THz-CCS) systems using broadband incoherent light as the pumping source have received increasing attention from researchers in recent years. However, a comprehensive and in-depth understanding of THz-CCS is still needed to obtain a detailed optimization scheme. Here we systematically investigate the influences of the detection parameters, light propagation process, and pump source on the CCS signals. The impacts of the filter slopes and time constants in lock-in detection are revealed for optimizing the signal-to-noise ratio and bandwidth of the THz signal. By varying the optical fiber length and dispersion coefficient, the dispersion insensitivity of THz-CCS was experimentally demonstrated. The comparison of different pump sources (SLD and ASE) shows that the over-wide and non-flat pump spectrum may attenuate the CCS signal because of the energy waste brought by the photomixing process under the limited bandwidth of the photomixer. Our research may lead to a deeper understanding and further optimization of the THz-CCS system, which will promote the development and widespread application of what is to the best of our knowledge a new technique.

9.
Gels ; 10(3)2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38534609

RESUMO

In the ancient Chinese recipe for composite mortar used in the construction of ground layers for architectural painting, the mixture of porcine blood and lime water is one of the constituent materials. Herein, according to the traditional recipe, the interaction between porcine blood and lime water was systematically and deeply investigated. The experimental investigation demonstrated that porcine blood mixed with lime water at the ratio found in the recipe can form a hydrogel with a hydrophobic surface. During air-drying, the lime water in porcine blood hydrogel can react with CO2 to form calcium carbonate. The crystal morphology of the formed calcium carbonate depends on the surrounding micro-environment of calcium ions in the porcine blood hydrogel. The formed morphology of calcium carbonate includes small calcite crystallites, small graininess calcite crystals with round features, calcite aggregates with layered ladder-like structures, and amorphous calcium carbonate (ACC). Interestingly, the calcium carbonate formed in the inner part of the porcine blood hydrogel exhibits lamellar distribution due to a Liesegang pattern formation. Based on the findings that the porcine blood hydrogel has surface hydrophobicity and brittleness, it can be predicted that in the preparation process of composite mortar for ancient building color painting base course, porcine blood used in the form of a hydrogel is not only easier to be dispersed in hydrophobic tung oil than in liquid porcine blood but also the affinity between porcine blood gel and tung oil is enhanced. As constituent material dispersed in the composite mortar, the layered distribution of calcium carbonate in the porcine blood hydrogel may presumably be beneficial to reduce the internal stress of the composite mortar material.

10.
Molecules ; 29(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38543001

RESUMO

The durability of wooden heritage objects and sites can be affected by external environmental factors, leading to decay, cracking, and other forms of deterioration, which might ultimately result in significant and irreversible loss. In this study, a FEVE resin was modified with Ag2O/OH-MWCNTS (MA), denoted as MAF, where three concentrations were prepared using in situ precipitation, and the resulting composite adhesive was characterized by a high viscosity and effective bacteriostatic properties, demonstrating a better viscosity and thermal stability, as well as antibacterial properties, than pure FEVE resin. The results show that MAF adhesives present good thermal stability, as evidenced by a lower mass loss rate following treatment at 800 °C compared to the pure FEVE resin. At a consistent shear rate, the viscosity of MAF demonstrates a notable increase with the proportion of MA, which is better than that of FEVE. This suggests that the nano-Ag2O particles in MA act as physical crosslinking agents in FEVE, improving the viscosity of the composite adhesive MAF. The adhesion strength between MAF and wood exhibits a similar trend, with wooden samples showing higher shear strengths as the proportion of MA increases in comparison to FEVE. Simultaneously, the antibacterial effects of the MAF adhesive exceeded 1 mm for Trichoderma, Aspergillus niger, and white rot fungi. The antibacterial activity of the MAF adhesive exhibited a direct correlation with the concentration of Ag2O/OH-MWCNTS, with the most pronounced inhibitory effect observed on Trichoderma. The MAF adhesive demonstrates promising prospects as an adhesive for wooden heritage artifacts, offering a novel approach for the rapid, environmentally friendly, and efficient development of composite adhesives with superior adhesive properties.

11.
Dig Dis Sci ; 69(3): 978-988, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341392

RESUMO

AIM: This study aimed to assess the effectiveness and safety of tenofovir alafenamide fumarate (TAF) in the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: We performed a meta-analysis of studies from the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), China Medical Information Network, and Wanfang databases. The databases were searched from inception to January 7, 2023, for cohort studies and randomized controlled trials (RCTs) comparing the use of TAF antivirals to other antivirals during pregnancy. We combined the data by means of a random-effect DerSimonian-Laird model and risk ratios (RRs) or a random-effect inverse variance model and standardized mean differences (SMDs) to determine the influence on mothers and infants. Our primary outcomes were infant weight, height, head size, birth defects, and Apgar scores. Additionally, we assessed whether newborns tested positive for hepatitis B surface antigen (HBsAg) at birth and at six months of age. The secondary outcomes of our investigation were alterations in levels of HBV deoxyribonucleic acid (DNA), alanine aminotransferase (ALT), total bilirubin (TBIL), blood creatinine, and urine ß2-microglobulin (ß2-M) in mothers. RESULTS: An extensive literature search identified 216 relevant publications; three cohort studies and two RCTs were included in this study. A total of 341 mothers were treated with TAF, and 342 were treated with other antiviral agents. TAF was as effective as other antiviral medications at lowering HBV MTCT rates at birth and at 6 months of age and ALT, TBIL, and HBV DNA levels. Moreover, compared with other antiviral drugs, TAF did not affect infant weight, height, head size, Apgar scores, and birth defects or maternal blood creatinine or ß2-M levels. CONCLUSIONS: TAF antiviral therapy during pregnancy was found to be safe for both mothers and fetuses.


Assuntos
Hepatite B Crônica , Hepatite B , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Adenina/efeitos adversos , Antivirais/efeitos adversos , Creatinina , DNA Viral , Fumaratos/efeitos adversos , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle
12.
Food Chem ; 444: 138667, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38335686

RESUMO

Iron-copper nanozymes (Fe-Cu NZs) with good peroxidase activity were prepared through hydrothermal method by using copper nitrate as copper source, iron acetate as iron source and 2, 5-dihydroxyterephthalic acid as organic ligand. Upon oxidation of the colourless TMB to light blue products by Fe-Cu NZs, the addition of Norfloxacin (NOR) resulted in a colour change to dark blue. The absorbance of the system correlated linearly with NOR concentration in the range of 3.3 µM to 66 µM, and the detection limit (LOD) was 0.386 µM. A rapid colourimetric assay for the determination of NOR in food matrices was developed, with a detection time of only one minute. Additionally, the assay facilitated the simultaneous catalytic degradation of NOR via Fe-Cu NZs. The primary degradation mechanism of NOR was identified as the transformation of the quinolone ring and the cleavage of the C9 = C10 double bond, which was substantiated by high-performance liquid chromatography (HPLC).


Assuntos
Norfloxacino , Quinolonas , Ferro/química , Cobre/química , Antioxidantes , Colorimetria/métodos , Peróxido de Hidrogênio
13.
Cancer Lett ; 587: 216730, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38360140

RESUMO

Under the sustained exposure to tumor microenvironment, effector lymphocytes may transform into the suppressive populations. γδ T cells are recognized as a crucial mediator and effector of immune surveillance and thereby a promising candidate for anti-tumor immunotherapy. Emerging clinical studies implicate that some γδ T subsets play an important role in promoting tumor progression. Our previous study identified an abnormal Vδ2+ T cells subset with regulatory features (Reg-Vδ2) in the patients with newly diagnosed acute myeloid leukemia (AML), and demonstrated that Reg-Vδ2 cells significantly suppressed the anti-AML effects of effector Vδ2 cells (Eff-Vδ2). The molecular mechanism underlying the subset transformation of Vδ2 cells remains unclear. Here, we found that the expression and activity of STAT5 were significantly induced in Reg-Vδ2 cells compared with Eff-Vδ2 cells, which was consistent with the differences found in primary Vδ2 cells between AML patients and healthy donors. In-vitro experiments further indicated that STAT5 was required for the induction of Reg-Vδ2 cells. The combined immunophenotypical and functional assays showed that blockage of STAT5 alleviated the immunosuppressive effect of Reg-Vδ2 cells on Eff-Vδ2 cells and enhanced the anti-AML capacity of Vδ2 cells from health donors and AML patients. Collectively, these results suggest that STAT5 acts as a critical regulator in the transformation of effector Vδ2 cells into a subset with immunosuppressive characteristics, providing a potential target for the improvement the efficacy of γδ T cells-based immunotherapy to treat AML and other hematologic malignancies.


Assuntos
Leucemia Mieloide Aguda , Subpopulações de Linfócitos T , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Fator de Transcrição STAT5/metabolismo , Microambiente Tumoral
14.
Curr Med Chem ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38231074

RESUMO

BACKGROUND: The proteins CDK4 and CDK6, which are extremely homologous, control cell cycle entry. For the treatment of breast tumors that include hormone receptors, CDK4 and CDK6 inhibitors have been authorized. The link between CDK4 and liver hepatocellular carcinoma (LIHC), however, has not yet been established. OBJECTIVE: The study aimed to explore the link between CDK4 and LIHC and the effect of CDK4 inhibitors on LIHC. METHOD: In this study, we have evaluated CDK4's prognostic relevance in LIHC using data from The Cancer Genome Atlas (TCGA). The relationship between clinical-pathologic features and CDK4 expression has been evaluated using the Kruskal-Wallis test, the Wilcoxon signed-rank test, and logistic regression. We have analyzed CDK4 and factors related to the prognosis of HCC using the Kaplan-Meier technique and multivariate Cox regression. Gene set enrichment analysis (GSEA) identified CDK4-related critical pathways. To investigate the connections between CDK4 and cancer immune infiltrates, TCGA data were employed in single-sample gene set enrichment analysis (ssGSEA). For functional validation, CDK4 was chosen since it can be inhibited by recognized CDK4/ 6-inhibitors (e.g., abemaciclib). RESULTS: Poorer overall and disease-specific outcomes were linked to high CDK4 expression in HCC patients. GSEA suggested that CDK4 and immune response are closely connected. The amount of Th2 cells infiltrating was positively correlated with CDK4 expression, while the amount of cytotoxic cells infiltrating was negatively correlated, according to ssGSEA. Both in vitro and in vivo, the anti-tumor efficacy of CDK4 inhibitor has been found to be superior to that of sorafenib. CONCLUSION: This study suggests a relationship between CDK4 and immune infiltration and prognosis in HCC. Additionally, a CDK4 inhibitor may have anti-tumor properties against hepatocellular cancer.

15.
N Engl J Med ; 390(3): 230-241, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38231624

RESUMO

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).


Assuntos
COVID-19 , Inibidores de Protease de Coronavírus , Adulto , Humanos , Administração Oral , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacologia , Antivirais/uso terapêutico , China , Proteínas M de Coronavírus/antagonistas & inibidores , Proteínas M de Coronavírus/metabolismo , Inibidores de Protease de Coronavírus/administração & dosagem , Inibidores de Protease de Coronavírus/efeitos adversos , Inibidores de Protease de Coronavírus/farmacologia , Inibidores de Protease de Coronavírus/uso terapêutico , COVID-19/metabolismo , COVID-19/terapia , Tratamento Farmacológico da COVID-19/métodos , Método Duplo-Cego , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Ritonavir/farmacologia , Ritonavir/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Fatores de Tempo , Combinação de Medicamentos
16.
Anal Methods ; 15(46): 6377-6384, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-37869902

RESUMO

Nicotine (NIC) is a harmful substance, drug, pesticide and chemical that is widely found in tobacco. It has carcinogenic, teratogenic and neurotoxic effects that have raised serious concerns. Herein, a colorimetric sensor with dual-ratio and dual-mode for the detection of NIC in tobacco samples was reported. The localized surface plasmon resonance signals of gold nanoparticles (AuNPs) and AuNPs-NIC are used as dual-ratio signals. The absorbance ratio of NIC to AuNPs or the absorbance ratio of NIC to AuNPs-NIC and the wavelength shift value of AuNPs-NIC are applied as dual-mode. Transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering spectroscopy, ultraviolet-visible spectrophotometry, cyclic voltammetry, and potentiostatic methods were used to characterize the sensor. Further analysis of NIC was conducted through morphological fitting and theoretical calculations. Under optimal conditions, the sensor shows a wide linear range of 5-500 µM. The detection limits for NIC are 2.48 µM, 1.63 µM and 1.34 µM, respectively. The experimental result shows that the dual-ratio signal of AuNPs and AuNPs-NIC has good selectivity and sensitivity, and can effectively reduce the interference of impurities on NIC detection. And the dual-mode of detection for NIC improves the accuracy and comparability of the result significantly. In addition, the proposed sensor was also applied to test NIC in tobacco samples with satisfactory recovery.


Assuntos
Nanopartículas Metálicas , Nicotina , Ouro/química , Nicotiana , Nanopartículas Metálicas/química , Colorimetria/métodos
17.
Lancet Reg Health West Pac ; 36: 100769, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37547039

RESUMO

Background: Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. Methods: A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Findings: Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n = 315) or EFV (n = 315) groups. The mean age was 30.6 ± 9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference: -4.7%, 95% CI: -9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p = 0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p < 0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p < 0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. Interpretation: The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Funding: Jiangsu Aidea Pharmaceutical Co., Ltd.

18.
Front Surg ; 10: 1067275, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37123539

RESUMO

Aim: To evaluate the impact of augmented reality surgical navigation (ARSN) technology on short-term outcomes of partial nephrectomy (PN). Methods: A systematic literature search was conducted in PubMed, Embase, Cochrane, and Web of Science for eligible studies published through March 28, 2022. Two researchers independently performed the article screening, data extraction and quality review. Data analysis was performed using Cochrane Review Manager software. Results: A total of 583 patients from eight studies were included in the analysis, with 313 in the ARSN-assisted PN group (AR group) and 270 in the conventional PN group (NAR group). ARSN-assisted PN showed better outcomes than conventional surgery in terms of operative time, estimated blood loss, global ischemia rate, warm ischemia time, and enucleation rate. However, there were no significant differences in the rate of Conversion to radical nephrectomy (RN), postoperative estimated glomerular filtration rate (eGFR), positive margin rate, and postoperative complication rate. Conclusion: The utilization of ARSN can improve the perioperative safety of PN. Compared with conventional PN, ARSN-assisted PN can reduce intraoperative blood loss, shorten operative time, and improve renal ischemia. Although direct evidence is lacking, our results still suggest a potential advantage of ARSN in improving renal recovery after PN. However, as the ARSN system is still in an exploratory stage, its relevance in PN have been poorly reported. Additional high-quality randomized controlled trial (RCT) studies will be required to confirm the effect of ARSN on PN. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=301798, identifier PROSPERO ID: CRD42022301798.

19.
Materials (Basel) ; 16(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36984017

RESUMO

Though previous studies have indicated that the fresh behaviours of plain mortar/concrete are mainly governed by the average water film thickness (AWFT), whether the concept of AWFT is also applicable to fibrous mortar/concrete still needs to be explored. Furthermore, for fibrous mortar/concrete, it is obvious that the fibres added also have certain effects on the fresh behaviours. In two previous studies on basalt fibre-reinforced mortar (BFRM), the integral effects of the AWFT and fibre dosage as well as the integral effects of the AWFT and fibre length were individually investigated. In this study, a fibre factor (FF) defined as the fibre volume multiplied by the fibre aspect ratio was employed and 24 extra mortar groups were tested. A total of 68 mortar groups were applied in numerical analysis. The results of the regression analysis yielded good correlations of the workability, fluidity, cohesiveness, and adhesiveness of BFRM with the AWFT and FF, suggesting that the AWFT and FF are together the governing parameters controlling the fresh behaviours of BFRM. Hence, the AWFT and FF may be used to develop a model for the fresh properties of BFRM.

20.
Front Public Health ; 11: 1078280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950094

RESUMO

Background: Previous studies have shown that serum albumin is associated with prostate cancer (PCa), but not with prostate-specific antigen (PSA) levels in populations without PCa history. Therefore, we analyzed secondary data provided by the National Health and Nutrition Examination Survey (NHANES) (2003-2010). Methods: In total, 5,469 participants were selected from the NHANES database (2003-2010). Serum albumin and PSA levels were serially considered independent and dependent variables, serially. A number of covariates were included in this study, including demographic, dietary, physical examination, and comorbidity data. Using weighted linear regression model and smooth curve fitting, the linear and non-linear relationship between serum albumin and PSA was investigated. Results: After modulating underlying interference factors, the weighted multivariate linear regression analysis revealed that serum albumin did not independently predict PSA levels (ß = -0.009 95%CI: -0.020, 0.002). Nevertheless, a non-linear relationship was found between serum albumin and PSA, with a point of 41 g/L. Left of the inflection point, the effect size, 95%CI, and P-value were 0.019 (log2 transformation) (-0.006, 0.043) and 0.1335, respectively. We found a negative association between serum albumin and PSA on the right side of the inflection point, with effect size, 95%CI, and a P-value of -0.022 (log2 transformation) (-0.037, -0.007), 0.0036. Conclusion: In summary, serum albumin and PSA levels are not linearly related. When serum albumin levels exceed 41 g, serum albumin levels are negatively associated with PSA levels.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Inquéritos Nutricionais , Albumina Sérica , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/diagnóstico , Modelos Lineares
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