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1.
Asian J Androl ; 26(4): 402-408, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38624195

RESUMO

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e ., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Docetaxel , Metanálise em Rede , Humanos , Masculino , Antagonistas de Androgênios/uso terapêutico , Androstenos/uso terapêutico , Androstenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Docetaxel/administração & dosagem , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Pirazóis , Ensaios Clínicos Controlados Aleatórios como Assunto , Tioidantoínas/uso terapêutico , Tioidantoínas/administração & dosagem
2.
Front Nutr ; 11: 1364866, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638295

RESUMO

Liver transplantation is an effective measure to treat adult-onset type II citrullinemia (CTLN2). Active and effective perioperative nutrition support is a very important treatment for the prognosis of such patients. In this paper, we analyzed the process, results, and outcome of nutritional support therapy in a case of CTLN2, and concluded that the perioperative nutritional support program for CTLN2 patients should be followed prior to surgery:1.because of the prevalence of severe malnutrition in CTLN2 patients, Enteral nutrition (EN) combined with Parenteral nutrition (PN) should be the first choice for nutritional support; 2. daily energy intake should be 35 ~ 40 kcal/kg; 3. the nutritional formula should be composed of low-carbohydrates and high medium-chain triglyceride (MCT). Postoperative: initiating EN as soon as possible is recommended to restore intestinal function and adjuvant PN might be taken into consideration in the early stage. The purpose of this case was to provide experience for the development and adjustment of the perioperative nutritional support regimen for CTLN2 patients.

3.
Molecules ; 28(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38067652

RESUMO

The flotation agent is an important collector in the production of potassium chloride and is brought into the crystallization stage with the reflux of the mother liquor. Octadecylamine Hydrochloride (ODA), 1-Dodecylamine Hydrochloride (DAH) and Sodium 1-dodecanesulfonate (SDS) were selected to study their effect on the nucleation of potassium chloride. Focused Beam Reflectance Measurement was used to collect the nucleation-induced periods of KCl in the presence of flotation agents at different supersaturations. Then, empirical equations, classical nucleation theory and growth mechanism equations were employed for data analysis. It was found that the presence of flotation agents increased the nucleation sequence m, and m(ODA) > m(SDS) > m(DAH) > m(H2O). In addition, the interfacial energy data obtained using classical nucleation theory suggest that the flotation agents used in our paper promoted the homogeneous nucleation of KCl (reduced from 5.3934 mJ·m-2 to 5.1434 mJ·m-2) and inhibited the heterogeneous nucleation of KCl (increased from 2.8054 mJ·m-2 to 3.6004 mJ·m-2). This investigation also revealed that the growth of potassium chloride was consistent with the 2D nucleation-mediated growth mechanism, and the addition of flotation agent did not change the growth mechanism of potassium chloride. Finally, the particle size distribution results were exactly consistent with the order of nucleation order m. The study of nucleation kinetics and growth mechanisms of different flotation agents on potassium chloride can provide guidance for optimizing the production process of potassium chloride and developing new flotation agents.

4.
Environ Sci Pollut Res Int ; 30(59): 124416-124424, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37996575

RESUMO

Chemical composition of the essential oil from Kochia scoparia (L.) Schrad. (syn. Bassia scoparia (L.) A. J. Scott) was analyzed in quality and quantity by GC-MS and GC-FID. Repellent activities of the essential oil from K. scoparia (KSEO) were evaluated against two common species of stored-product insects Tribolium castaneum Herbst and Liposcelis bostrychophila Badonnel. Results indicated that KSEO mainly consisted of eugenol, ß-caryophyllene, and α-humulene, accounting for 75.6%, 8.2%, and 1.4% of the total oil, respectively. KSEO and the three major components were repellent to T. castaneum and L. bostrychophila adults. Notably, KSEO exerted significant effects, comparable to the positive control DEET at 2 and 4 h post-exposure. Eugenol at 63.17-2.53 nL/cm2 exhibited high percentage repellency ranging from 96 to 70% against L. bostrychophila during 4-h exposure. To gain further insights into the repellent activity, molecular docking simulation was performed with eugenol as the ligand and an odorant binding protein TcOBPC12 (gene: TcOBP10B) from the model insect T. castaneum as the receptor. Docking calculation results revealed that TcOBPC12 had binding affinity to eugenol (△G = - 4.52 kcal/mol) along with a hydrogen bond of 0.18 nm (1.8 Å) long forming between them, which could be an important target protein associated with identifying volatile repellent molecules. This work highlights the promising potential of KSEO as a botanical repellent for controlling stored-product insects.


Assuntos
Bassia scoparia , Repelentes de Insetos , Inseticidas , Óleos Voláteis , Tribolium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Eugenol/farmacologia , Simulação de Acoplamento Molecular , Insetos , Repelentes de Insetos/farmacologia , Repelentes de Insetos/química , Inseticidas/química
5.
PLoS One ; 18(9): e0290869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37656682

RESUMO

We investigate the roles of liquidity and delay in financial markets through our proposed optimal forecasting model. The efficiency and liquidity of the financial market are examined using stochastic models that incorporate information delay. Based on machine learning, we estimate the in-sample and out-of-sample forecasting price performances of the six proposed methods using the likelihood function and Bayesian methods, and the out-of-sample prediction performance is compared with the benchmark model ARIMA-GARCH. We discover that the forecasting price performance of the proposed simplified delay stochastic model is superior to that of the benchmark methods by the test methods of a variety of loss function, superior predictive ability test (SPA), Akaike information criterion (AIC), and Bayesian information criterion (BIC). Using data from the Chinese stock market, the best forecasting model assesses the efficiency and liquidity of the financial market while accounting for information delay and trade probability. The rise in trade probability and delay time affects the stability of the return distribution and raises the risk, according to stochastic simulation. The empirical findings show that empirical and best forecasting approaches are compatible, that company size and liquidity (delay time) have an inverse relationship, and that delay time and liquidity have a nonlinear relationship. The most efficient have optimal liquidity.


Assuntos
Comércio , Previsões , Modelos Econômicos , Teorema de Bayes , Benchmarking , Funções Verossimilhança , Previsões/métodos , China , Processos Estocásticos , Aprendizado de Máquina , Comércio/economia , Comércio/tendências
6.
Front Physiol ; 14: 1123182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37650112

RESUMO

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relative toxin removal methods, and elucidate promising approaches to effectively remove toxins.

7.
Pak J Med Sci ; 39(3): 875-879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37250570

RESUMO

Objective: To investigate the correlation between dyslipidemia and carotid intima-media thickness (IMT) in patients with diabetes mellitus. Methods: A descriptive research design was adopted in this study. One hundred and twenty patients with Type-2 diabetes mellitus who were admitted to the physical examination center of The Fourth Hospital of Hebei Medical University from June 2020 to June 2021 for physical examination were recruited to the experimental group. The 120 patients were divided into three groups according to carotid IMT: normal group, thickened group, and plaque group. Forty healthy people who underwent a physical examination during the same period were recruited as the control group. The differences in IMT in various parts of the experimental group and the control group and the differences in blood lipid indexes were compared and analyzed. In addition, the correlation between mean IMT of bilateral common carotid arteries and blood lipid levels in normal, thickened and plaque groups was compared and analyzed. Results: The intima-media thicknesses of the internal carotid artery and bilateral common carotid arteries of the patients in the experimental group were significantly thicker than those in the healthy control group, the levels of TC, TG and LDL were higher than those in the control group, while the level of HDL was lower than that in the control group, with a statistically significant difference (p=0.00). The levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and LDL were positively correlated with the mean IMT of bilateral common carotid arteries (p<0.05), while the level of HDL was negatively correlated with the mean IMT of bilateral common carotid arteries (p<0.05). Conclusion: Dyslipidemia and glucose metabolism in patients with Type-2 diabetes mellitus have a close bearing on carotid IMT. Clinically, patients with Type-2 diabetes mellitus can be judged by monitoring carotid IMT for dyslipidemia, atherosclerosis and other related complications.

8.
Ren Fail ; 45(1): 2190815, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37051665

RESUMO

Excessive daytime sleepiness (EDS) is associated with quality of life and all-cause mortality in the end-stage renal disease population. This study aims to identify biomarkers and reveal the underlying mechanisms of EDS in peritoneal dialysis (PD) patients. A total of 48 nondiabetic continuous ambulatory peritoneal dialysis patients were assigned to the EDS group and the non-EDS group according to the Epworth Sleepiness Scale (ESS). Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the differential metabolites. Twenty-seven (male/female, 15/12; age, 60.1 ± 16.2 years) PD patients with ESS ≥ 10 were assigned to the EDS group, while twenty-one (male/female, 13/8; age, 57.9 ± 10.1 years) PD patients with ESS < 10 were defined as the non-EDS group. With UHPLC-Q-TOF/MS, 39 metabolites with significant differences between the two groups were found, 9 of which had good correlations with disease severity and were further classified into amino acid, lipid and organic acid metabolism. A total of 103 overlapping target proteins of the differential metabolites and EDS were found. Then, the EDS-metabolite-target network and the protein-protein interaction network were constructed. The metabolomics approach integrated with network pharmacology provides new insights into the early diagnosis and mechanisms of EDS in PD patients.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Falência Renal Crônica , Diálise Peritoneal Ambulatorial Contínua , Diálise Peritoneal , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/métodos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Distúrbios do Sono por Sonolência Excessiva/epidemiologia
9.
J Integr Plant Biol ; 65(7): 1636-1650, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36866859

RESUMO

Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the tandem CCCH zinc-finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30-demethylase-like genes, GmJMJ30-1 and GmJMJ30-2, are involved in this demethylation process. Overexpression of GmJMJ30-1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield-related agronomic traits were evaluated in stable GmZF351-transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30-GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.


Assuntos
Secas , Glycine max , Glycine max/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cloreto de Sódio/farmacologia , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico , Zinco/metabolismo , Regulação da Expressão Gênica de Plantas
10.
Sci Total Environ ; 869: 161562, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638990

RESUMO

In this research, the performance of biochar-enhanced agricultural application of food waste liquid digestate for celery cultivation was investigated to reveal its utilization potential and environmental impacts. Liquid digestate demonstrated a good agronomic effect, with a significant fertilization efficiency of 42.3 % during celery growth. With liquid digestate addition (270 t/ha), the same level of harvested celery yield of 15,345 kg/ha was achieved compared with chemical fertilizer utilization of 15,495 kg/ha. Based on the same nitrogen input, the liquid digestate application increased the sugar content of the harvested celery (7 %-15 %) while decreasing the nitrate content (29 %-45 %). The harvested celery with liquid digestate application indicated higher contents of total nitrogen, total phosphorus and total potassium levels than those in the chemical fertilizer group. Liquid digestate as a fertilizer supplemented the soil with nutrients, including phosphorus, potassium and organic matter, but did not cause excessive accumulation. The inorganic nitrogen content of the leachate increased as applied liquid digestate increased. However, it remained 20 %-60 % lower than that of chemical fertilizer at the same fertilization efficiency. After applying liquid digestate, there was no significant increase was observed in soil salinity. The coupled addition of biochar helps to improve the overall effects of liquid digestate for agricultural application and reduce negative environmental impacts. This study demonstrates that returning liquid digestate to agricultural fields as fertilizer is an environmentally and economically beneficial practice.


Assuntos
Apium , Eliminação de Resíduos , Fertilizantes/análise , Anaerobiose , Solo/química , Nitrogênio/análise , Verduras , Fósforo , Potássio
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 122-127, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647654

RESUMO

Objective: To isolate extracellular vesicles (EVs) from Mycobacterium tuberculosis ( Mtb), to examine their morphology, particle size, and distribution, to study the effect of EVs derived from Mtb ( Mtb-EVs) on intracellular reactive oxygen species (ROS) production and cytokine secretion in dendritic cells (DCs), and to make preliminary exploration of Mtb-EVs' effect on the immune regulation of DCs. Methods: Mtb-EVs were obtained by ultrafiltration concentration and the protein concentration was determined by BCA assay. The morphology of Mtb-EVs was observed through negative staining electron microscopy (EM). The particle size distribution and concentration of Mtb-EVs were determined by nanoparticle tracking analysis (NTA). Mouse bone marrow was isolated through sterile procedures and mice myeloid DCs were induced and amplified by the combined use of recombinant mouse granulocyte-macrophage colony-stimulating factor (rm GM-CSF) and recombinant mouse interleukin-4 (rm IL-4). Then, morphological and immunophenotypic characterization was performed. After that, the DCs were treated with Mtb-EVs at different concentrations and CCK-8 assay was done to measure their effect on the survival rate of DCs and to identify the appropriate stimulation concentration for subsequent experimental procedures. The intracellular ROS levels of DCs were evaluated with DCFH-DA fluorescence probe and the cytokine secretion of DCs was determined by ELISA. Results: EM observation showed that Mtb-EVs isolated by ultrafiltration concentration were spherical vesicles of varied sizes, all being approximately 100 nm in diameter and displaying typical morphology. NTA results from NanoSight nanoparticle tracker showed that the peak particle size was 98.5 nm, that the average particle size was 110.2 nm, and that the particle size was mainly distributed between 68.4-155.7 nm. Mtb-EVs that were smaller than 250 nm accounted for 98.39% of the total. Mouse myeloid DCs directionally induced and amplified in vitro displayed typical DC phenotype and morphology, and the purity exceeded 85%. EM verified the abundance of microvilli and radial protuberance on the surface of DCs, which had uniform cytoplasm and clear nuclear membrane. Loaded with Mtb-EVs at different concentrations, including 10 2, 10 3, and 10 4 particles/cell, the DCs had significantly upregulated levels of intracellular ROS ( P<0.05). In addition, Mtb-EVs induced the release of IL-1ß and IL-6 in a dose-dependent manner ( P<0.05). Conclusion: We established in the study a technical process for the extraction of Mtb-EVs by ultrafiltration concentration and obtained Mtb-EVs with sound morphology, high purity, and concentrated particle size distribution. Furthermore, Mtb-EVs can upregulate the intracellular ROS level in DCs and induce the release of IL-1ß and IL-6 in a dose-dependent manner.


Assuntos
Mycobacterium tuberculosis , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Medula Óssea , Interleucina-6/metabolismo , Células Dendríticas
12.
Asian J Androl ; 25(4): 520-527, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36629156

RESUMO

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center (Shanghai, China) were reviewed. The following body composition parameters were calculated using computed tomography: skeletal muscle index (SMI), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI). Pretreatment serum adipocytokine levels, including interleukin 6, insulin, leptin, monocyte chemoattractant protein-1, adiponectin, and resistin, were measured using the multiplex bead-based immunoassays. Cox regression and Kaplan-Meier methods were used for survival analyses. Of the 453 mCRPC patients initially identified, 105 were included in the analysis. High VATI group patients had longer PFS (median, 10 months vs 7 months, P = 0.008) and OS (median, 24 months vs 15 months, P = 0.017), compared with low VATI group patients. SMI and SATI were not significantly associated with PFS or OS. Of the six detected adipocytokines, only leptin was associated with mCRPC prognosis. High leptin group patients had shorter PFS (median, 7 months vs 12 months, P = 0.0018) and OS (median, 17 months vs 22 months, P = 0.042), compared with low leptin group patients. Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS, while a high leptin level was an independent risk factor for PFS and OS. Therefore, VATI and serum leptin levels could provide important information concerning mCRPC prognosis.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Docetaxel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Leptina , Adipocinas , Resultado do Tratamento , China , Prognóstico , Estudos Retrospectivos , Antígeno Prostático Específico
13.
Plant Physiol ; 191(1): 496-514, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36377782

RESUMO

Plant flavonoids are valuable natural antioxidants. Sweet potato (Ipomoea batatas) leaves are rich in flavonoids, regenerate rapidly, and can adapt to harsh environments, making them an ideal material for flavonoid biofortification. Here, we demonstrate that the B-box (BBX) family transcription factor IbBBX29 regulates the flavonoid contents and development of sweet potato leaves. IbBBX29 was highly expressed in sweet potato leaves and significantly induced by auxin (IAA). Overexpression of IbBBX29 contributed to a 21.37%-70.94% increase in leaf biomass, a 12.08%-21.85% increase in IAA levels, and a 31.33%-63.03% increase in flavonoid accumulation in sweet potato, whereas silencing this gene produced opposite effects. Heterologous expression of IbBBX29 in Arabidopsis (Arabidopsis thaliana) led to a dwarfed phenotype, along with enhanced IAA and flavonoid accumulation. RNA-seq analysis revealed that IbBBX29 modulates the expression of genes involved in the IAA signaling and flavonoid biosynthesis pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay indicated that IbBBX29 targets key genes of IAA signaling and flavonoid biosynthesis to activate their expression by binding to specific T/G-boxes in their promoters, especially those adjacent to the transcription start site. Moreover, IbBBX29 physically interacted with developmental and phenylpropanoid biosynthesis-related proteins, such as AGAMOUS-LIKE 21 protein IbAGL21 and MYB308-like protein IbMYB308L. Finally, overexpressing IbBBX29 also increased flavonoid contents in sweet potato storage roots. These findings indicate that IbBBX29 plays a pivotal role in regulating IAA-mediated leaf development and flavonoid biosynthesis in sweet potato and Arabidopsis, providing a candidate gene for flavonoid biofortification in plants.


Assuntos
Arabidopsis , Ipomoea batatas , Ipomoea batatas/genética , Ipomoea batatas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Flavonoides/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas
14.
Infect Drug Resist ; 15: 7219-7226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36533251

RESUMO

Purpose: Infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great challenge. Central nervous system (CNS) infection caused by CRKP is rarely reported, and effective treatment is limited. Thus, this study aimed to assess intrathecal (IT) or intraventricular (IVT) injection of tigecycline for clearing infection with CRKP in CNS. Patients and Methods: Two patients who had intracranial infection with CRKP after craniotomy were treated in our institution and analyzed retrospectively, summarizing their therapeutic schedules. Results: They all had a fever with the positive results of cerebrospinal fluid (CSF) test, and CSF culture showed positive for CPKP, which was sensitive only to tigecycline. In addition, the MIC of polymyxin B was not tested due to the limited laboratory conditions. After IT or IVT injection of tigecycline treatment, the temperature of the patients became normal in 3 days, with normal levels of white blood cells, protein, glucose and chlorine concentrations in the CSF. Crucially, twice CSF cultures also became negative with no clinical symptoms of intracranial infection after IT or IVT injection of tigecycline treatment. Moreover, there were no adverse drug reactions observed. Conclusion: IT or IVT injection of tigecycline may be a bright choice to control intracranial infection with CRKP.

15.
J Immunother Cancer ; 10(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35537782

RESUMO

BACKGROUND: Dual blockade of immune checkpoint and angiogenesis is an effective strategy for multiple cancers. Camrelizumab is a monoclonal antibody against PD-1, and famitinib is a multitargeted receptor tyrosine kinase inhibitor with antiangiogenesis and antiproliferation activities against tumor cells. We conducted an open-label, multicenter phase 2 basket study of camrelizumab and famitinib in eight cohorts of genitourinary or gynecological cancers. Here, findings in cohort of advanced or metastatic urothelial carcinoma with platinum-progressive disease (cohort 2) are presented. METHODS: Patients who had progressed after platinum-based chemotherapy for advanced or metastatic disease or had progressed within 12 months after completion of platinum-based (neo)adjuvant therapy were given camrelizumab (200 mg intravenously every 3 weeks) plus famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Totally, 36 patients were recruited. With a median duration from enrollment to data cut-off of 11.9 months (range 6.1-28.5), ORR was 30.6% (95% CI 16.3% to 48.1%). Median duration of response (DoR) was 6.3 months (95% CI 2.1 to not reached). Median progression-free survival (PFS) was 4.1 months (95% CI 2.2 to 8.2), and median overall survival (OS) was 12.9 months (95% CI 8.8 to not reached). Patients with bladder cancer (n=18) had numerically better outcomes, with an ORR of 38.9% (95% CI 17.3% to 64.3%) and a median PFS of 8.3 months (95% CI 4.1 to not reached). Median DoR and OS in this subpopulation had not been reached with lower limit of 95% CI of 4.2 months for DoR and 11.3 months for OS, respectively. Of 36 patients, 22 (61.1%) had grade 3 or 4 treatment-related adverse events, mainly decreased platelet count and hypertension. CONCLUSIONS: Camrelizumab plus famitinib showed potent antitumor activity in advanced or metastatic urothelial carcinoma patients after platinum-based chemotherapy. Patients with bladder cancer seemed to have better response to this combination. TRIAL REGISTRATION NUMBER: NCT03827837.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Feminino , Humanos , Indóis , Masculino , Platina/farmacologia , Platina/uso terapêutico , Pirróis , Neoplasias da Bexiga Urinária/tratamento farmacológico
16.
J Clin Pharmacol ; 62(9): 1160-1169, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35396702

RESUMO

Irinotecan-induced hepatotoxicity can cause severe clinical complications in patients; however, the underlying mechanism and factors affecting hepatotoxicity have rarely been investigated. In this cross-sectional study, we screened all clinical, demographic, medication, and genetic variables among 126 patients receiving irinotecan and explored potential associations with the incidence and time to onset of irinotecan-induced hepatotoxicity. Approximately 38.9% of the patients suffered from hepatotoxicity after irinotecan administration. The presence of cardiovascular diseases increases the incidence of hepatotoxicity ≈2.9-fold and doubles the hazard of time to hepatotoxicity. Patients with liver metastasis had a >4-fold higher risk of hepatotoxicity and a 3.5-fold increased hazard of time to hepatotoxicity compared to those without liver metastasis. Patients who took cytochrome P450 (CYP) 3A inducers had a 4.4-fold increased incidence of hepatotoxicity, and furthermore, concomitant use of platinum-based antineoplastics revealed 4.2 times the hazard of time to hepatotoxicity compared to those receiving antimetabolites. The cumulative dose of irinotecan (5-9 cycles) increased hepatotoxicity by 8.5 times. However, the genotypes and phenotypes of UGT1A1*28/*6 failed to be predictive factors of hepatotoxicity. The findings of this study suggest that irinotecan-induced hepatotoxicity is not directly associated with genetic variables but is mostly related to concomitant use of CYP3A4 inducers and platinum, as well as the presence of liver metastasis and cardiovascular disease. Thus, close monitoring of liver function is recommended, especially in patients with liver impairment or using CYP3A inducers and platinum antineoplastic drugs, which may be the best way to prevent hepatotoxicity.


Assuntos
Antineoplásicos , Doença Hepática Induzida por Substâncias e Drogas , Neoplasias Hepáticas , Antineoplásicos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , China/epidemiologia , Estudos Transversais , Citocromo P-450 CYP3A/genética , Indutores do Citocromo P-450 CYP3A , Interações Medicamentosas , Humanos , Irinotecano/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico
18.
J Biomater Appl ; 36(8): 1444-1457, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34995470

RESUMO

The aim of this study was to develop nanostructured-lipid carriers (NLC) encapsulated by Chitosan hydrogel beads for the efficient topical carrier. Dynamic light scattering (DLS), X-ray diffraction (XRD), Differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were conducted to study the influence of the encapsulation on the characteristic of resveratrol-loaded NLC, and the results showed that there was no impact on resveratrol-loaded NLC. Chitosan hydrogel beads could significantly improve the physical stability of resveratrol-loaded NLC. In vitro release study revealed that resveratrol-loaded NLC-Chitosan hydrogel beads had a more significant sustained-release effect on resveratrol. In vitro transdermal studies suggested that the skin permeation of resveratrol was promoted by the effect of Chitosan hydrogel beads and increased resveratrol distribution in the skin. In vitro cytotoxicity showed that resveratrol-loaded NLC-Chitosan hydrogel beads did not exert a hazardous effect on L929 cells. Hence, NLC-Chitosan hydrogel beads might be a promising method for topical applications of resveratrol.


Assuntos
Quitosana , Nanoestruturas , Portadores de Fármacos/química , Hidrogéis/química , Lipídeos/química , Tamanho da Partícula , Resveratrol
19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(6): 803-806, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-37308439

RESUMO

Objective: To investigate the effects of bosutinib on the early stage of cerebral ischemia-reperfusion injury in rats. Methods: Forty Sprague-Dawley rats were randomly divided into four groups (random number method), 10 rats in each group; sham group (control group): only neck vessels were isolated without other treatments; MCAO (model group): the rat brain ischemia/reperfusion injury model was made by a modified wire bolus method,ischemia for 2 h followed by reperfusion for 24 h; DMSO group (solvent group): DMSO ( 0.752 ml/kg) was injected into the tail vein one day before the experiment, brain ischemia 2 h reperfusion for 24 h; Bosutinib group (intervention group): one day before the experiment, the tail vein was injected with Bosutinib (4 mg/kg), brain ischemia 2 h reperfusion for 24 h. After 24 h of ischemia reperfusion, neurological function score was performed; brain infarct area was calculated after staining with TTC; SIK2 was detected by Western blot; the contents of TNF-α and IL-6 in brain tissue were detected by ELISA. Results: Compared with the sham group, the neurological function scores, the infarct volume percentages and the levels of inflammatory factors IL-6 and TNF-α of the MCAO and DMSO groups were increased significantly (P<0.05 or P<0.01). Compared with the MCAO and DMSO groups, the above mentioned indexes of the bosutinib group were all decreased significantly (P<0.05 or P< 0.01). Compared with sham group, the expression levels of SIK2 protein in MCAO and DMSO groups had no significant changes(P> 0.05); compared with the MCAO and DMSO group, the expression level of SIK2 protein in the bosutinib group was decreased significantly (P<0.05). Conclusion: Bosutinib reduces cerebral ischemia-reperfusion-induced injury, and its possible mechanism is related to the decreased expression of SIK2 protein and inflammatory factors.


Assuntos
Dimetil Sulfóxido , Traumatismo por Reperfusão , Ratos , Animais , Ratos Sprague-Dawley , Interleucina-6 , Fator de Necrose Tumoral alfa , Proteínas Serina-Treonina Quinases
20.
IEEE Trans Pattern Anal Mach Intell ; 44(11): 7380-7399, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648430

RESUMO

Drones, or general UAVs, equipped with cameras have been fast deployed with a wide range of applications, including agriculture, aerial photography, and surveillance. Consequently, automatic understanding of visual data collected from drones becomes highly demanding, bringing computer vision and drones more and more closely. To promote and track the developments of object detection and tracking algorithms, we have organized three challenge workshops in conjunction with ECCV 2018, ICCV 2019 and ECCV 2020, attracting more than 100 teams around the world. We provide a large-scale drone captured dataset, VisDrone, which includes four tracks, i.e., (1) image object detection, (2) video object detection, (3) single object tracking, and (4) multi-object tracking. In this paper, we first present a thorough review of object detection and tracking datasets and benchmarks, and discuss the challenges of collecting large-scale drone-based object detection and tracking datasets with fully manual annotations. After that, we describe our VisDrone dataset, which is captured over various urban/suburban areas of 14 different cities across China from North to South. Being the largest such dataset ever published, VisDrone enables extensive evaluation and investigation of visual analysis algorithms for the drone platform. We provide a detailed analysis of the current state of the field of large-scale object detection and tracking on drones, and conclude the challenge as well as propose future directions. We expect the benchmark largely boost the research and development in video analysis on drone platforms. All the datasets and experimental results can be downloaded from https://github.com/VisDrone/VisDrone-Dataset.


Assuntos
Algoritmos , Dispositivos Aéreos não Tripulados , Fotografação
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