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1.
Fitoterapia ; 176: 106007, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744384

RESUMO

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

2.
Molecules ; 29(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611749

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a high degree of malignancy and poor prognosis. Tumor-associated macrophages (TAMs) have been identified as significant contributors to the growth and metastasis of TNBC through the secretion of various growth factors and chemokines. Salvianolic acid A (SAA) has been shown to have anti-cancer activities. However, the potential activity of SAA on re-polarized TAMs remains unclear. As there is a correlation between the TAMs and TNBC, this study investigates the effect of SAA on TAMs in the TNBC microenvironment. For that purpose, M2 TAM polarization was induced by two kinds of TNBC-conditioned medium (TNBC-TCM) in the absence or presence of SAA. The gene and protein expression of TAM markers were analyzed by qPCR, FCM, IF, ELISA, and Western blot. The protein expression levels of ERK and p-ERK in M2-like TAMs were analyzed by Western blot. The migration and invasion properties of M2-like TAMs were analyzed by Transwell assays. Here, we demonstrated that SAA increased the expression levels of CD86, IL-1ß, and iNOS in M2-like TAMs and, conversely, decreased the expression levels of Arg-1 and CD206. Moreover, SAA inhibited the migration and invasion properties of M2-like TAMs effectively and decreased the protein expression of TGF-ß1 and p-ERK in a concentration-dependent manner, as well as TGF-ß1 gene expression and secretion. Our current findings for the first time demonstrated that SAA inhibits macrophage polarization to M2-like TAMs by inhibiting the ERK pathway and promotes M2-like TAM re-polarization to the M1 TAMs, which may exert its anti-tumor effect by regulating M1/M2 TAM polarization. These findings highlight SAA as a potential regulator of M2 TAMs and the possibility of utilizing SAA to reprogram M2 TAMs offers promising insights for the clinical management of TNBC.


Assuntos
Ácidos Cafeicos , Lactatos , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fator de Crescimento Transformador beta1 , Microambiente Tumoral , Macrófagos Associados a Tumor
3.
PLoS One ; 19(4): e0301834, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593111

RESUMO

BACKGROUND: Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. MATERIALS AND METHODS: We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). RESULTS: We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. CONCLUSIONS: Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.


Assuntos
Neoplasias Ósseas , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Gástricas , Adolescente , Humanos , Adulto , Pontuação de Propensão , Programa de SEER , Estimativa de Kaplan-Meier , Prognóstico , Neoplasias Ósseas/secundário
4.
World J Diabetes ; 15(2): 129-132, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38464368

RESUMO

The global diabetes surge poses a critical public health challenge, emphasizing the need for effective glycemic control. However, rapid correction of chronic hyperglycemia can unexpectedly trigger microvascular complications, necessitating a reevaluation of the speed and intensity of glycemic correction. Theories suggest swift blood sugar reductions may cause inflammation, oxidative stress, and neurovascular changes, resulting in complications. Healthcare providers should cautiously approach aggressive glycemic control, especially in long-standing, poorly controlled diabetes. Preventing and managing these complications requires a personalized, comprehensive approach with education, monitoring, and interdisciplinary care. Diabetes management must balance short and long-term goals, prioritizing overall well-being. This editorial underscores the need for a personalized, nuanced approach, focusing on equilibrium between glycemic control and avoiding overcorrection.

5.
World J Diabetes ; 15(2): 137-141, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38464375

RESUMO

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a pivotal intervention in diabetes management, offering significant cardiovascular benefits. Empagliflozin, in particular, has demonstrated cardioprotective effects beyond its glucose-lowering action, reducing heart failure hospitalizations and improving cardiac function. Of note, the cardioprotective mechanisms appear to be inde-pendent of glucose lowering, possibly mediated through several mechanisms involving shifts in cardiac metabolism and anti-fibrotic, anti-inflammatory, and anti-oxidative pathways. This editorial summarizes the multifaceted cardiovascular advantages of SGLT2 inhibitors, highlighting the need for further research to elucidate their full therapeutic potential in cardiac care.

6.
J Am Chem Soc ; 146(11): 7341-7351, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38442250

RESUMO

The C2H2 separation from CO2 and C2H4 is of great importance yet highly challenging in the petrochemical industry, owing to their similar physical and chemical properties. Herein, the pore nanospace engineering of cage-like mixed-ligand MFOF-1 has been accomplished via contracting the size of the pyridine- and carboxylic acid-functionalized linkers and introducing a fluoride- and sulfate-bridging cobalt cluster, based on a reticular chemistry strategy. Compared with the prototypical MFOF-1, the constructed FJUT-1 with the same topology presents significantly improved C2H2 adsorption capacity, and selective C2H2 separation performance due to the reduced cage cavity size, functionalized pore surface, and appropriate pore volume. The introduction of fluoride- and sulfate-bridging cubane-type tetranuclear cobalt clusters bestows FJUT-1 with exceptional chemical stability under harsh conditions while providing multiple potential C2H2 binding sites, thus rendering the adequate ability for practical C2H2 separation application as confirmed by the dynamic breakthrough experiments under dry and humid conditions. Additionally, the distinct binding mechanism is suggested by theoretical calculations in which the multiple supramolecular interactions involving C-H···O, C-H···F, and other van der Waals forces play a critical role in the selective C2H2 separation.

7.
Heliyon ; 10(3): e25289, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333785

RESUMO

The present investigation aims to design and development of hybrid zinc oxide (ZnO) and manganese dioxide (MnO2) nanoparticles (NPs) doped-biopolymer matrix-based cost-effective technique for the synthesis of biocompatible Kaolinite/Chitosan (Ka/CS) nanocomposites (NCs) could be used as agents for wound healing due to their efficiency and low toxicity. The crystallite size, phase purity and surface morphology of the synthesised NCs were investigated systemic analytical methods. The results revealed that the metal oxide nanocomposites presented that in rod-crystalline in shape and additionally exhibits that 20-30 nm in size. In vitro antibacterial analyses demonstrates that NCs have significantly improved bactericidal inhibition efficiency when compared to the bare hybrid NPs and polymeric components. The in vitro biocompatibility observation demonstrates that prepared hybrid-NPs encapsulated NCs have enhanced cell survival rate (>90 %), which was established by MTT assay and Live/Dead fluorescence assay methods at different incubation time. The DPPH assay was used to investigate the synergistic effects of prepared dressing materials increased antioxidant activity. Preliminary research indicates that these nanocomposites, ZnO/MnO2 incorporated and decorated with Ka/CS NCs, could be a significant promoter and potential candidate for use as a robust wound healing agent in post-operative nursing care.

8.
Adv Sci (Weinh) ; 11(13): e2308123, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240582

RESUMO

Fluoro- and chlorofluorocabons (FC/CFCs) are important refrigerants, solvents, and fluoropolymers in industry while being toxic and carrying high global warming potential. Detection and reclamation of FC/CFCs based on adsorption technology with highly selective adsorbents is important to labor safety and environmental protection. Herein, the study reports an integrated method to combine capture, separation, enrichment, and analysis of representative FC/CFCs (chlorodifluoromethane(R22) and 1,1,1,2-tetrafluoroethane (R134a)) by using the highly stable and porous Zr-MOF, DUT-67. Gas adsorption and breakthrough experiments demonstrate that DUT-67 has high R22/R134a uptake (124/116 cm3 g-1) and excellent R22/R134a/CO2 separation performance (IAST selectivities of R22/CO2 and R134a/CO2 ranging from 51.4 to 33.3, and 31.1 to 25.8), even in rather low concentration and humid conditions. A semi-quantitative analysis protocol is set up to analyze the low concentrations of R22/R134a based on the high selective R22/R134a adsorption ability, fast adsorption kinetics, water-resistant utility, facile regeneration, and excellent recyclability of DUT-67. In situ single-crystal X-ray diffraction, theoretical calculations, and in situ diffuse reflectance infrared Fourier transform spectra have been employed to understand the adsorption mechanism. This work may provide a potential adsorbent for purge and trap technique under room temperature, thus promoting the application of MOFs for VOCs sampling and quantitative analysis.

9.
Phys Chem Chem Phys ; 26(7): 6008-6021, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38293905

RESUMO

Fluorescence resonance energy transfer (FRET) is an important mechanism to design ratiometric fluorescent probes that are able to detect analytes quantitatively according to the ratio of two well-resolved emission signals. Two-photon (TP) fluorescent probes can realize the detection in living cells and tissues with deeper penetration depth, higher resolution, and lower photodamage in contrast to one-photon fluorescent probes. However, to date, fabricating TP-FRET ratiometric fluorescent probes possessing large two-photon absorption (TPA), high fluorescence quantum yield and perfect FRET efficiency is still challenging. Consequently, to develop excellent TP-FRET ratiometric probes and explore the relationship between their molecular structures and TP fluorescence properties, in this paper, we designed a series of H2S-detecting TP fluorescent probes employing the FRET mechanism based on an experimental probe BCD. Thereafter, we comprehensively evaluated the TP sensing performance of these probes by means of time-dependent density functional theory and quadratic response theory. Furthermore, we determined energy transfer efficiency and fluorescence quantum yield. Significantly, through regulating benzene-fused positions, we successfully improved fluorescence quantum yield and TPA cross-section simultaneously. Large spectral overlap between energy donor emission and acceptor absorption was achieved and near perfect energy transfer efficiency was acquired for all the studied probes. We revealed that these probes exhibit two well-resolved TPA bands, which are contributed by FRET donors and acceptors, respectively. Especially, both the wavelengths and the cross-sections of the two TPA bands agree well with those of energy donors and acceptors, which is the unique TPA spectral profile of FRET probes and has never been previously reported. Moreover, we proposed an excellent TP-FRET probe BCD3 and its product molecule BCD3-H2S, which exhibit large Stokes (141 nm and 88 nm) and emission shifts (5931 cm-1), as well as greatly increased TP action cross-sections (24-fold and 60-fold) in the near-infrared region with respect to BCD and BCD-H2S. Our detailed study can give an insight into the efficient design of novel TP-FRET fluorescent probes.

10.
Mol Ther ; 32(3): 766-782, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38273656

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.


Assuntos
Fibrose Pulmonar Idiopática , Macrófagos , Humanos , Camundongos , Animais , Modelos Animais de Doenças , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose , DNA , Bleomicina
11.
ACS Appl Mater Interfaces ; 16(1): 847-852, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38153916

RESUMO

Acetylene (C2H2) is widely used as a raw material for producing various downstream commodities in the petrochemical and electronic industry. Therefore, the acquisition of high-purity C2H2 from a C2H2/CO2 mixture produced by partial methane combustion or thermal hydrocarbon cracking is of great significance yet highly challenging due to their similar physical and chemical properties. Herein, we report an anionic metal-organic framework (MOF) named LIFM-210, which has Li+ cations in the pores and shows a higher adsorption affinity for C2H2 than CO2. LIFM-210 is constructed by a unique tetranuclear Ni(II) cluster acting as a 10-connected node and an organic ligand acting as a 5-connected node. Single-component adsorption and transient breakthrough experiments demonstrate the good C2H2 selective separation performance of LIFM-210. Theoretical calculations revealed that Li+ ions strongly prefer C2H2 to CO2 and are primary adsorption sites, playing vital roles in the selective separation of C2H2/CO2.

12.
J Agric Food Chem ; 71(40): 14458-14470, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37782011

RESUMO

It is important to develop new insecticides with a new mode of action because of increasing pesticide resistance. In this study, a series of novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Bioassays indicated that the 24 compounds synthesized possessed excellent insecticidal activity against Mythimna separate and no activity against Aphis craccivora and Tetranychus cinnabarinus. Among these aryl isoxazoline derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)-N-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-carboxamide (IA-8) had the best insecticidal activity against M. separate, which is comparable with the positive control fluralaner. The molecular docking results of compound IA-8 and fluralaner with the GABA model demonstrated the same docking mode between compound IA-8 and positive control fluralaner in the active site of GABA. Molecular structure comparisons and ADMET analysis can potentially be used to design more active compounds. The structure-activity relationships are also discussed. This work provided an excellent insecticide for further optimization.


Assuntos
Inseticidas , Animais , Inseticidas/química , Simulação de Acoplamento Molecular , Desenho de Fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Ácido gama-Aminobutírico
13.
J Gastroenterol ; 58(12): 1167-1177, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37777987

RESUMO

BACKGROUND: The application of vonoprazan significantly improved the eradication rate of Helicobacter pylori (H. pylori). This study aimed to compare efficacy and safety of the 10-day vonoprazan-amoxicillin (VA) and 14-day rabeprazole-amoxicillin (RA) dual therapy, and to provide a more efficient, safer, and convenient dual regimen for H. pylori infection. METHODS: This was a prospective, open-label, multi-center, randomized controlled study of treatment-naive patients with H. pylori infection. The participants were randomly assigned to the 10-day VA group with vonoprazan 20 mg Bid plus amoxicillin 1 g Tid or the 14-day RA group with rabeprazole 10 mg Tid plus amoxicillin 1 g Tid. The effectiveness, the adverse events, and the patient compliance of the two groups were compared. RESULTS: A total of 690 patients were enrolled. The eradication rates of 10-day VA and 14-day RA dual therapy were 89.3% and 84.9% in intention-to-treat (ITT) analysis (P = 0.088); 90.6% and 85.9% by modified intention-to-treat (mITT) analysis (P = 0.059); 91.4% and 86.6% by per-protocol (PP) analysis (P = 0.047). Non-inferiority was confirmed between the two groups (all P < 0.001). No discernible differences were observed in adverse effects and compliance between groups. Poor compliance reduced the eradication efficacy (P < 0.05). CONCLUSIONS: The 10-day VA dual therapy was non-inferior to the 14-day RA dual therapy for H. pylori treatment-naive patients, which should be given priority in the first-line treatment. The application of vonoprazan reduced treatment course and antibiotic use. Patients' adherence was crucial for the success of eradication.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Rabeprazol/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Claritromicina/uso terapêutico , Quimioterapia Combinada , Antibacterianos/efeitos adversos , Amoxicilina/efeitos adversos , Resultado do Tratamento
14.
J Neuroinflammation ; 20(1): 138, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37268957

RESUMO

BACKGROUND: Multiple sclerosis (MS) leads to demyelination and neurodegeneration with autoimmune responses in central nervous system. Patients begin with a relapsing-remitting (RR) course, and more than 80% of them may advance to secondary progressive MS (SPMS), which is characteristic for the gradual decline of neurological functions without demonstrated treating method to prevent. This study aims to investigate the contribution of peripheral CD8 + T cells during the conversion from RRMS to SPMS, as well as reveal potential diagnostic signature in distinguishing SPMS. METHODS: Single-cell RNA sequencing was employed to reveal the heterogeneity of CD8 + T cells between SPMS and RRMS. In addition, flow cytometry was used to further characterized CD8 + T cell dynamic changes in patients. T cell receptor sequencing was performed to detect the clonal expansion of MS. Using Tbx21 siRNA, T-bet was confirmed to manipulate GzmB expression. The correlation between GzmB + CD8 + T cell subsets and clinical characteristics of MS and their potential diagnostic value for SPMS were evaluated by generalized linear regression models and receiver operating characteristic (ROC) curve respectively. RESULTS: Other than diminished naïve CD8 + T cell, elevating of activated CD8 + T cell subsets were observed in SPMS patients. Meanwhile, this aberrant amplified peripheral CD8 + T cells not only exhibited terminal differentiated effector (EMRA) phenotype with GzmB expression, but also possessed distinct trajectory from clonal expansion. In addition, T-bet acted as a key transcriptional factor that elicited GzmB expression in CD8 + TEMRA cells of patients with SPMS. Finally, the expression of GzmB in CD8 + T cells was positively correlated with disability and progression of MS, and could effectively distinguish SPMS from RRMS with a high accuracy. CONCLUSIONS: Our study mapped peripheral immune cells of RRMS and SPMS patients and provided an evidence for the involvement of GzmB + CD8 + TEMRA cells in the progression of MS, which could be used as a diagnostic biomarker for distinguishing SPMS from RRMS.


Assuntos
Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Granzimas , Esclerose Múltipla Crônica Progressiva/diagnóstico , Linfócitos T CD8-Positivos , Subpopulações de Linfócitos T , Esclerose Múltipla Recidivante-Remitente/diagnóstico
15.
ACS Appl Mater Interfaces ; 15(25): 30394-30401, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37327481

RESUMO

The separation of CO2 from the industrial post-combustion flue gas is of great importance to reduce the increasingly serious greenhouse effect, yet highly challenging due to the extremely high stability, low cost, and high separation performance requirements for adsorbents under the practical operating conditions. Herein, we report a robust squarate-cobalt metal-organic framework (MOF), FJUT-3, featuring an ultra-small 1D square channel decorated with -OH groups, for CO2/N2 separation. Remarkably, FJUT-3 not only has excellent stability under harsh chemical conditions but also presents low-cost property for scale-up synthesis. Moreover, FJUT-3 shows excellent CO2 separation performance under various humid and temperature conditions confirmed by the transient breakthrough experiments, thus enabling FJUT-3 with adequate potentials for industrial CO2 capture and removal. The distinct CO2 adsorption mechanism is well elucidated by theoretical calculations, in which the hierarchical C···OCO2, C-O···CCO2, and O-H···OCO2 interactions play a vital synergistic role in the selective CO2 adsorption process.

16.
Inorg Chem ; 62(21): 8058-8063, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37172273

RESUMO

The development of metal-organic framework (MOF) adsorbents with a potential molecule sieving effect for CO2 capture and separation from flue gas is of critical importance for reducing the CO2 emissions to the atmosphere yet challenging. Herein, a cagelike MOF with a suitable cage window size falling between CO2 and N2 and the cavity has been constructed to evaluate its CO2/N2 separation performance. It is noteworthy that the introduction of coordinated dimethylamine (DMA) and N,N'-dimethylformamide (DMF) molecules not only significantly reduces the cage window size but also enhances the framework-CO2 interaction via C-H···O hydrogen bonds, as proven by molecular modeling, thus leading to an improved CO2 separation performance. Moreover, transient breakthrough experiments corroborate the efficient CO2/N2 separation, revealing that the introduction of DMA and DMF molecules plays a vital role in the separation of a CO2/N2 gas mixture.

17.
Clin Transl Gastroenterol ; 14(7): e00602, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37235793

RESUMO

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.


Assuntos
Antiulcerosos , Úlcera Duodenal , Humanos , Lansoprazol/efeitos adversos , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/induzido quimicamente , Antiulcerosos/efeitos adversos , Método Duplo-Cego
18.
Talanta ; 262: 124684, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37220689

RESUMO

Uracil-DNA glycosylase (UDG) is pivotal in maintaining genome integrity and aberrant expressed UDG is highly relevant to numerous diseases. Sensitive and accurate detecting UDG is critically significant for early clinical diagnosis. In this research, we demonstrated a sensitive UDG fluorescent assay based on rolling circle transcription (RCT)/CRISPR/Cas12a-assisted bicyclic cascade amplification strategy. Target UDG catalyzed to remove uracil base of DNA dumbbell-shape substrate probe (SubUDG) to produce an apurinic/apyrimidinic (AP) site, at which SubUDG was cleaved by apurinic/apyrimidinic endonuclease (APE1) subsequently. The exposed 5'-PO4 was ligated with the free 3'-OH terminus to form an enclosed DNA dumbbell-shape substrate probe (E-SubUDG). E-SubUDG functioned as a template can actuate T7 RNA polymerase-mediated RCT signal amplification, generating multitudes of crRNA repeats. The resultant Cas12a/crRNA/activator ternary complex activated the activity of Cas12a, causing a significantly enhanced fluorescence output. In this bicyclic cascade strategy, target UDG was amplified via RCT and CRISPR/Cas12a, and the whole reaction was completed without complex procedures. This method enabled sensitive and specific monitor UDG down to 0.0005 U/mL, screen corresponding inhibitors, and analyze endogenous UDG in A549 cells at single-cell level. Importantly, this assay can be extended to analyze other DNA glycosylase (hAAG and Fpg) by altering the recognition site in DNA substrates probe rationally, thereby offering a potent tool for DNA glycosylase-associated clinical diagnosis and biomedical research.


Assuntos
Técnicas Biossensoriais , Uracila-DNA Glicosidase , Uracila-DNA Glicosidase/metabolismo , Sistemas CRISPR-Cas , Limite de Detecção , DNA/genética , Sondas de DNA , Técnicas Biossensoriais/métodos
19.
BMC Urol ; 23(1): 56, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016405

RESUMO

OBJECTIVE: To compare the clinical efficiency and safety of emergency extracorporeal shock wave lithotripsy (eESWL) and delayed extracorporeal shock wave lithotripsy (dESWL) in the treatment of ureteral stones. METHODS: Cochrane Library, PubMed, Google Scholar, and Web of Science were searched from January 1, 1992 to September 30, 2022, and all comparative studies involving eESWL and dESWL for ureteral calculi were included. Statistical analysis was performed using Review Manager 5.3 software. Funnel plot was used to evaluated publication bias. RESULTS: A total of 9 articles involving 976 patients diagnosed with ureteral stones were included. The results showed that the stone-free rate (SFR) after four weeks was significantly higher in the eESWL group than in the dESWL group [relative risk (RR) = 1.22, 95% confidence interval (CI): 1.13-1.32, P < 0.01]. In subgroup analysis of different stone locations, proximal ureteral calculi [RR = 1.25, 95% CI: 1.14-1.38, P < 0.01] and mid-to-distal ureteral calculi [RR = 1.18, 95% CI: 1.03-1.34, P < 0.05] all showed a higher SFR in the eESWL group. eESWL significantly shortened the stone-free time(SFT) [mean difference (MD) = -5.75, 95% CI: -9.33 to -2.17, P < 0.01]. In addition, eESWL significantly reduced auxiliary procedures [RR = 0.53, 95% CI: 0.40-0.70, P < 0.01]. No significant difference in complications was found between the two groups [RR = 0.90, 95% CI: 0.69-1.16, P > 0.05]. CONCLUSION: eESWL can significantly improve SFR, shorten SFT, and reduce auxiliary procedures.


Assuntos
Litotripsia , Cálculos Ureterais , Humanos , Cálculos Ureterais/terapia , Litotripsia/métodos , Resultado do Tratamento
20.
Acad Radiol ; 30 Suppl 2: S114-S126, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37003874

RESUMO

RATIONALE AND OBJECTIVES: This study assessed the role of second-look automated breast ultrasound (ABUS) adjunct to mammography (MAM) versus MAM alone in asymptomatic women and compared it with supplementing handheld ultrasound (HHUS). MATERIALS AND METHODS: Women aged 45 to 64 underwent HHUS, ABUS, and MAM among six hospitals in China from 2018 to 2022. We compared the screening performance of three strategies (MAM alone, MAM plus HHUS, and MAM plus ABUS) stratified by age groups and breast density. McNemar's test was used to assess differences in the cancer detection rate (CDR), the false-positive biopsy rate, sensitivity, and specificity of different strategies. RESULTS: Of 19,171 women analyzed (mean [SD] age, 51.54 [4.61] years), 72 cases of breast cancer (3.76 per 1000) were detected. The detection rates for both HHUS and ABUS combined with MAM were statistically higher than those for MAM alone (all p < 0.001). There was no significant difference in cancer yields between the two integration strategies. The increase in CRD of the integrated strategies was higher in women aged 45-54 years with denser breasts compared with MAM alone (all p < 0.0167). In addition, the false-positive biopsy rate of MAM plus ABUS was lower than that of MAM plus HHUS (p = 0.025). Moreover, the retraction in ABUS was more frequent in cases detected among MAM-negative results. CONCLUSION: Integrated ABUS or HHUS into MAM provided similar CDRs that were significantly higher than those for MAM alone in younger women (45-54 years) with denser breasts. ABUS has the potential to avoid unnecessary biopsies and provides specific image features to distinguish malignant tumors from HHUS.


Assuntos
Neoplasias da Mama , Ultrassonografia Mamária , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia Mamária/métodos , Sensibilidade e Especificidade , Mamografia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , China/epidemiologia
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