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1.
Artigo em Inglês | MEDLINE | ID: mdl-39327693

RESUMO

BACKGROUND: To evaluate the cost-effectiveness of first-line sintilimab plus chemotherapy versus chemotherapy for advanced esophageal squamous cell carcinoma (ESCC) from the perspective of the Chinese health service system. METHODS: A partitioned survival model was constructed to simulate quality-adjusted life years and incremental cost-effectiveness ratios over a patient's lifetime based on a phase III clinical trial. RESULTS: Sintilimab plus chemotherapy increased by 0.316 QALY and 0.285 QALY with the additional cost of $5692 and $5269, which led to the ICER of $18000/QALY and $18519/QALY gained in the overall population and the patients with CPS ≥ 10, respectively. CONCLUSIONS: Compared with chemotherapy alone, sintilimab may be a cost-effective first-line treatment choice for locally advanced or metastatic ESCC.

2.
Huan Jing Ke Xue ; 45(9): 5351-5360, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323153

RESUMO

The unique geographical and climatic conditions in the Three-River Headwaters Region gave birth to distinctive plant species and vegetation types. To reveal the spatial distribution of plant communities and soil habitats along the riparian zone of the Sanjiangyuan Region and their influencing mechanisms, 14 survey plots were set up (ten from the Yangtze River source, two from the Lancang River source, and two from the Yellow River source), and the effects of soil nutrient characteristics (especially soil phosphorus morphology), climate factors, and river topography on plant community characteristics were quantitatively analyzed. The results showed that the plant community composition in the riparian zone of the source of the three rivers was dominated by perennial herbs (72.2%), followed by annual herbs (20.4%) and shrubs (7.4%). The dominant plants were Stipa purpurea, Polygonum orbiculatum, Carex parvula, Potentilla anserina, and Gentiana straminea. The average plant coverage, Shannon-Wiener index, and Pielou index were (64.4% ±23.6%), (1.31 ±0.42), and (0.84 ±0.08), respectively. The plant community diversity index was the highest in the Yangtze River source, followed by that in the Lancang River source, and the lowest in the Yellow River source. The soil pH of the riparian zone of the Yangtze River source was significantly higher than that of the Lancang River source, whereas the mean contents of organic matter, total nitrogen, and Fe-Al combined phosphorus were significantly lower than those of the Lancang River source. The calcium and magnesium-combined phosphorus was the main form of phosphorus in riparian soil (63.89%). Temperature, soil organic phosphorus content, and pH had significant effects on plant composition in the riparian zone of the Three-River Headwaters Region, whereas soil calcium and magnesium-combined phosphorus content had significant effects on plant community diversities. These results may deepen the scientific understanding of the evolution trend and genetic mechanism of plant communities in the riparian zone of the Three-River Headwaters Region.


Assuntos
Ecossistema , Fósforo , Rios , Solo , China , Solo/química , Fósforo/análise , Plantas/classificação , Desenvolvimento Vegetal , Monitoramento Ambiental , Dinâmica Populacional , Biodiversidade , Poaceae/crescimento & desenvolvimento , Análise Espacial
3.
J Hazard Mater ; 479: 135672, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236546

RESUMO

Vibrio spp., known as significant marine pathogens, have become more prevalent due to global warming. Antibiotics released into the environment drive Vibrio resistance. The increasing consumption of seafood leads to more interactions between Vibrio and humans. Despite this concerning trend, there remains a lack of large-scale surveillance for Vibrio contamination across various types of food. This study isolated 4027 Vibrio strains, primarily comprising V. parahaemolyticus and V. alginolyticus, in 3581 fresh shrimp and meat products from 2013 to 2022. The Vibrio strains showed increased resistance to important antibiotics, especially ß-lactams used to treat foodborne bacterial infections. Whole genome sequencing of 591 randomly chosen strains showed a strong correlation between antibiotic resistance and genotypes in Vibrio. Notably, various ESBL genes have evolved over the past 8 years, with blaVEBs being the most dominant. Additionally, carbapenemase genes, such as blaNDM-1, have become increasingly prevalent in recent years. Various mobile genetic elements, including IncQ and IncA/C plasmids, recoverable in Vibrio, facilitate the transmission of crucial ß-lactamase genes. These data provide insights into the evolutionary traits of antimicrobial resistance in foodborne Vibrio strains over a decade. Policymakers should consider these findings when devising appropriate strategies to combat bacterial antimicrobial resistance and safeguard human health.


Assuntos
Antibacterianos , Microbiologia de Alimentos , Vibrio , China , Antibacterianos/farmacologia , Vibrio/genética , Vibrio/efeitos dos fármacos , beta-Lactamases/genética , Farmacorresistência Bacteriana/genética , Alimentos Marinhos/microbiologia , Animais , Genoma Bacteriano , Sequenciamento Completo do Genoma , Testes de Sensibilidade Microbiana
4.
Eur J Surg Oncol ; 50(12): 108658, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39244978

RESUMO

BACKGROUND: Oxidative stress significantly influences the development and progression of gastric cancer (GC). It remains unreported whether incorporating oxidative stress factors into nomograms can improve the predictive accuracy for survival and recurrence risk in GC patients. METHODS: 3498 GC patients who underwent radical gastrectomy between 2009 and 2017 were enrolled and randomly divided into training cohort (TC) and internal validation cohort (IVC). Cox regression analysis model was used to evaluate six preoperative oxidative stress indicators to formulate the Systemic oxidative stress Score (SOSS). Two nomograms based on SOSS was constructed by multivariate Cox regression and validated using 322 patients from another two hospitals. RESULTS: A total of 3820 patients were included. The SOSS, composed of three preoperative indicators-fibrinogen, albumin, and cholesterol-was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS). The two nomograms based on SOSS showed a significantly higher AUC than the pTNM stage (OS: 0.830 vs. 0.778, DFS: 0.824 vs. 0.775, all P < 0.001) and were validated in the IVC and EVC (all P < 0.001). The local recurrence rate, peritoneal recurrence rate, distant recurrence rate and multiple recurrence rate in high-risk group were significantly higher than those in low-risk group (P < 0.05). CONCLUSIONS: The two novel nomograms based on SOSS which was a combination score of three preoperative blood indicators, demonstrated outstanding predictive abilities for both survival and recurrence in GC patients with different risk groups, which may potentially improve survival through perioperatively active intervention strategies and individualized postoperatively close surveillance.

7.
Inorg Chem ; 63(36): 16878-16887, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39190825

RESUMO

Effective CO2 transformations hold essential significance for carbon neutrality and sustainable energy development. Carboxylative cyclization of propargylic amines with CO2 serves as an atom-economic reaction to afford oxazolidinones, showing broad applications in organic synthesis and pharmaceutical fields. However, most catalysts involved noble metals, exhibited low efficiency, or required large amounts of base. Hence, it is imperative to explore alternative noble-metal-free catalysts in order to achieve efficient conversion while minimizing the use of additives. Herein, a novel nanopore-based Cu(II)-organic framework (1) based on a new imidazole carboxylic ligand was successfully constructed and exhibited excellent stability. Catalytic investigations revealed that the combination of 1 with 1,4-diaza[2.2.2]bicyclooctane (DABCO) efficiently catalyzed the carboxylative cyclization of propargylic amines with CO2, achieving turnover numbers of 142 based on the catalyst and 7.1 based on DABCO. 1 as a heterogeneous catalyst maintained high catalytic performance even after being reused at least 5 cycles, with its structure remaining stable. The strong activation of Cu(II) cluster nodes of catalyst 1 toward -NH- groups within organic substrates, as demonstrated by mechanism experiments, along with excellent CO2 adsorption performance and the presence of regular 1D channels, synergistically facilitates the reaction rate. This research presents the first instance of a Cu(II)-organic framework achieving this cyclization reaction, offering wide prospects for novel catalyst design and CO2 utilization.

8.
Front Public Health ; 12: 1421826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135924

RESUMO

Objective: This study focuses on assessing the cost-effectiveness of incorporating toripalimab alongside chemotherapy for the treatment of patients diagnosed with metastatic triple-negative breast cancer from the perspective of the Chinese healthcare system. Methods: A partitioned survival model was constructed to simulate the costs and health outcomes over the lifetime of patients with mTNBC. Clinical data regarding overall survival, progression-free survival, and treatment-related adverse events were derived from the TORCHLIGHT clinical trials. Incremental cost-effectiveness ratio (ICER) were calculated based on the gains in quality-adjusted life-year (QALY). The willingness-to-pay (WTP) threshold was defined as $39,855.79 per QALY. Additionally, sensitivity analyses were conducted to examine the robustness of the model. Results: The total cost incurred by the group receiving toripalimab was $38,040.62, while the placebo plus chemotherapy was $26,102.07. The utilization of the toripalimab regimen resulted in an increase of 0.74 QALYs and an incremental cost of $11,938.55 compared to the placebo plus chemotherapy group. The ICER was $16,133.18/QALY, indicating that toripalimab plus chemotherapy is a cost-effective strategy according to the WTP threshold. Sensitivity analyses confirmed the robustness of the results. Conclusion: This study suggests that the addition of toripalimab to chemotherapy for the treatment of mTNBC is a cost-effective strategy. The findings provide valuable evidence to guide decision-making regarding treatment selection for patients with mTNBC in China.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Pessoa de Meia-Idade , China , Adulto , Análise de Custo-Efetividade
9.
Sci Rep ; 14(1): 20105, 2024 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-39209973

RESUMO

Improving fattening efficiency is an important goal of breeding commercial pigs, especially for the large-scale pig farms. Fattening efficiency index (FEI) can be used to evaluate the fattening efficiency. The aim of this study was to identify the factors affecting the fattening efficiency of commercial pigs in large-scale pig farms and further study the impact of these factors on the production performance of commercial pig batches at different production levels. The data of 9,570 batches was mainly consisted of four parts (farm facilities, general information of piglets, production performance of nursery pigs and finishing pigs). A total of 28 variables were evaluated by the multi-variable linear regression models. The differences in production factors significantly correlated with FEI at piglets-finishing stage were compared among high-performing (HP), moderate-performing (MP), and low-performing (LP) batches of commercial pigs during the nursery and finishing stage. Among the 28 variables, 18 were significantly correlated with fattening efficiency (P < 0.05), including 11 continuous variables and seven discrete variables. The significant differences among the 11 consecutive variables in the HP, MP, and LP batches of commercial pigs mostly persisted from the piglets-nursery stage to the growing-finishing stage, ultimately affecting the FEI at piglets-finishing stage. For the seven significant discrete variables, the HP batches had a lower proportions in owned source of piglets, number of the purchasing piglets in spring and winter, number of batches in the East and North regions and five-way crossbred pigs, while a higher proportions in the use of closed circuit television video (CCTV) and wastes treatment system. The fattening efficiency of commercial pigs in large-scale pig farms was comprehensively affected by farm facilities, piglets, and production performance at nursery and finishing stage. The low fattening efficiency may have started at the end of nursery stage.


Assuntos
Criação de Animais Domésticos , Animais , Suínos , Criação de Animais Domésticos/métodos , Fazendas , Cruzamento , Feminino , Masculino
10.
Expert Rev Pharmacoecon Outcomes Res ; 24(8): 1017-1025, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38979829

RESUMO

OBJECTIVE: This study aims to conduct a cost-effectiveness analysis of pembrolizumab in combination with chemotherapy for HER2-negative advanced gastric cancer in China. METHODS: A partitioned survival approach model was constructed to simulate the progression of HER2-negative advanced gastric cancer and evaluate the outcomes of different treatment strategies. We calculated incremental cost-effectiveness ratios (ICER) to assess the cost associated with each quality-adjusted life-year (QALY) gained. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess robustness and reliability. RESULTS: The analysis conducted in the base case demonstrated that the ICER associated with pembrolizumab was $177405.83/QALY gained in all population. In the subgroup analysis, it was found that individuals with a PD-L1 CPS ≥ 1 and those with a PD-L1 CPS ≥ 10 had ICERs of $152397.06/QALY and $109534.13/QALY, respectively. All ICER values for both the all population groups and the subgroups exceeded the WTP threshold in China. Our analysis shows the robustness of these results, as they remained consistent when input parameters were varied within a ± 25% range. CONCLUSION: The findings of this cost-effectiveness analysis suggest that pembrolizumab in combination with chemotherapy is not a cost-effective treatment option for HER2-negative advanced gastric cancer in China.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Receptor ErbB-2 , Neoplasias Gástricas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Humanos , China , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Receptor ErbB-2/metabolismo , Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/administração & dosagem , Progressão da Doença , Reprodutibilidade dos Testes , Antígeno B7-H1/metabolismo , Feminino , Análise de Custo-Efetividade
11.
Front Pharmacol ; 15: 1396761, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005941

RESUMO

Background: This study aims to systematically analyze the cost-effectiveness of the combination therapy comprising sugemalimab and chemotherapy in the management of advanced ESCC from the Chinese healthcare system perspective. Methods: An advanced ESCC patient simulation partitioned survival approach model was developed to mimic the disease progression of patients undergoing treatment with sugemalimab in combination with chemotherapy versus chemotherapy alone. To ensure accuracy and precision, clinical data, treatment costs, and utility values were collected from comprehensive clinical trials and reliable economic databases. The cost-effectiveness analysis was conducted by assessing the incremental cost-effectiveness ratio in relation to the established willingness-to-pay threshold. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model. Results: The cumulative expenditure for the group of patients administered with sugemalimab amounted to US$ 41734.87, whereas the placebo group was associated with a total cost of US$ 22926.25. By evaluating the ICER, which quantifies the additional cost incurred per QALY gained, a value of US$ 61066.96 per QALY was determined. It is imperative to note that this ICER value surpasses the predetermined threshold for WTP in China, set at US$ 39,855.79 per QALY. Sensitivity analyses demonstrated that the results were sensitive to the cost of sugemalimab, progression-free survival, and utility values. These fluctuations did not result in a reversal of the study findings. Conclusion: The combination of sugemalimab with chemotherapy for the treatment of ESCC in China is currently not considered a cost-effective therapeutic approach. However, it is suggested that additional reductions in price may facilitate the potential for achieving cost-effectiveness.

12.
J Am Med Inform Assoc ; 31(10): 2315-2327, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38900207

RESUMO

OBJECTIVE: Although supervised machine learning is popular for information extraction from clinical notes, creating large annotated datasets requires extensive domain expertise and is time-consuming. Meanwhile, large language models (LLMs) have demonstrated promising transfer learning capability. In this study, we explored whether recent LLMs could reduce the need for large-scale data annotations. MATERIALS AND METHODS: We curated a dataset of 769 breast cancer pathology reports, manually labeled with 12 categories, to compare zero-shot classification capability of the following LLMs: GPT-4, GPT-3.5, Starling, and ClinicalCamel, with task-specific supervised classification performance of 3 models: random forests, long short-term memory networks with attention (LSTM-Att), and the UCSF-BERT model. RESULTS: Across all 12 tasks, the GPT-4 model performed either significantly better than or as well as the best supervised model, LSTM-Att (average macro F1-score of 0.86 vs 0.75), with advantage on tasks with high label imbalance. Other LLMs demonstrated poor performance. Frequent GPT-4 error categories included incorrect inferences from multiple samples and from history, and complex task design, and several LSTM-Att errors were related to poor generalization to the test set. DISCUSSION: On tasks where large annotated datasets cannot be easily collected, LLMs can reduce the burden of data labeling. However, if the use of LLMs is prohibitive, the use of simpler models with large annotated datasets can provide comparable results. CONCLUSIONS: GPT-4 demonstrated the potential to speed up the execution of clinical NLP studies by reducing the need for large annotated datasets. This may increase the utilization of NLP-based variables and outcomes in clinical studies.


Assuntos
Neoplasias da Mama , Aprendizado de Máquina Supervisionado , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/classificação , Feminino , Processamento de Linguagem Natural , Conjuntos de Dados como Assunto , Registros Eletrônicos de Saúde , Mineração de Dados/métodos
13.
Sci Rep ; 14(1): 13370, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862511

RESUMO

Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the independent impacts of age, period, and cohort on the trends. HBV data were collected from the China Information System for Disease Control and Prevention. Joinpoint regression was utilized to examine temporal trends, and an age-period-cohort model was employed to estimate the effects of age, period, and cohort. A total of 327,585 HBV cases were included in this study. The incidence of chronic and acute HB showed a decreasing trend in Guangzhou over the past 15 years, with an average annual percent change of - 4.31% and - 16.87%, respectively. Age, period, and cohort all exerted significant effects. The incidence of HB was higher in males than in females and non-central areas compared to central areas. Age groups of 0-4 years and 15-24 years were identified as high-risk groups. The period relative risks for chronic HB incidence decreased initially and then stabilized. Cohorts born later had lower risks. Chronic HB incidences remain high in Guangzhou, especially among males, younger individuals, and residents of non-central areas. More efforts are still needed to achieve hepatitis elimination targets.


Assuntos
Hepatite B , Humanos , China/epidemiologia , Feminino , Masculino , Incidência , Adolescente , Adulto , Pessoa de Meia-Idade , Lactente , Criança , Pré-Escolar , Adulto Jovem , Hepatite B/epidemiologia , Recém-Nascido , Idoso , Fatores Etários , Efeito de Coortes , Vírus da Hepatite B , Fatores de Risco
14.
Microbes Infect ; : 105380, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909679

RESUMO

Acinetobacter baumannii (AB) infections have become a global public health concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of AB strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.33%) being carbapenem-resistant AB (CRAB), with the main mechanism being the carriage of the blaOXA-23 gene. The overall mortality rate of patients caused by such strains was 15.21% (n = 33). Artificial lung ventilation and the use of meropenem were mortality risk factors in AB-infected patients, while KL2 AB infection was negatively associated. Core genome multilocus sequence typing and clustering analysis were performed on the integrated AB genome collection from the NCBI database and this study to illustrate the population structure among China. The results revealed diverse core genome profiles (n = 17) among AB strains from China, and strains from this single hospital exhibited most of the core genome profiles (n = 13), suggesting genetic variability within the hospital and transmission across the country. These findings show that the high transmission potential of the CRAB strains and meropenem usage that confers a selective advantage of CRAB clinically are two major factors that pose significant challenges to the effective clinical management of AB infections. Understanding the genetic features and transmission patterns of clinical AB strains is crucial for the effective control of infections caused by this pathogen.

15.
J Med Chem ; 67(13): 10687-10709, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38913701

RESUMO

UC and ALI are inflammatory diseases with limited treatment in the clinic. Herein, fragment-based anti-inflammatory agent designs were carried out deriving from cyclohexylamine/cyclobutylamine and several fragments from anti-inflammatory agents in our lab. AF-45 (IC50 = 0.53/0.60 µM on IL-6/TNF-α in THP-1 macrophages) was identified as the optimal molecule using ELISA and MTT assays from the 33 synthesized compounds. Through mechanistic studies and a systematic target search process, AF-45 was found to block the NF-κB/MAPK pathway and target IRAK4, a promising target for inflammation and autoimmune diseases. The selectivity of AF-45 targeting IRAK4 was validated by comparing its effects on other kinase/nonkinase proteins. In vivo, AF-45 exhibited a good therapeutic effect on UC and ALI, and favorable PK proprieties. Since there are currently no clinical or preclinical trials for IRAK4 inhibitors to treat UC and ALI, AF-45 provides a new lead compound or candidate targeting IRAK4 for the treatment of these diseases.


Assuntos
Lesão Pulmonar Aguda , Colite Ulcerativa , Quinases Associadas a Receptores de Interleucina-1 , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Humanos , Animais , Colite Ulcerativa/tratamento farmacológico , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Desenho de Fármacos , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Descoberta de Drogas , Masculino , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Relação Estrutura-Atividade , Células THP-1
16.
Inorg Chem ; 63(25): 11554-11565, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38815997

RESUMO

Efficient and multiple CO2 utilization into high-value-added chemicals holds significant importance in carbon neutrality and industry production. However, most catalysis systems generally exhibit only one type of CO2 transformation with the efficiency to be improved. The restricted abundance of active catalytic sites or an inefficient utilization rate of these sites results in the constraint. Consequently, we designed and constructed two metal hydrogen-bonded organic frameworks (M-HOFs) {[M3(L3-)2(H2O)10]·2H2O}n (M = Co (1), Ni (2); L = 1-(4-carboxyphenyl)-1H-pyrazole-3,5-dicarboxylic acid) in this research. 1 and 2 are well-characterized, and both show excellent stability. The networks connected by multiple hydrogen bonds enhance the structural flexibility and create accessible Lewis acidic sites, promoting interactions between the substrates and catalytic centers. This enhancement facilitates efficient catalysis for two types of CO2 transformations, encompassing both cycloaddition reactions with epoxides and aziridines to afford cyclic carbonates and oxazolidinones. The catalytic activities (TON/TOF) are superior compared with those of most other catalysts. These heterogeneous catalysts still exhibited high performance after being reused several times. Mechanistic studies indicated intense interactions between the metal sites and substrates, demonstrating the reason for efficient catalysis. This marks the first instance on M-HOFs efficiently catalyzing two types of CO2 conversions, finding important significance for catalyst design and CO2 utilization.

17.
Int J Food Microbiol ; 418: 110734, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38759293

RESUMO

This study reports a comprehensive epidemiological and genetic analysis of V. cholerae strains, specifically non-O1/non-O139 serogroups, isolated from animal-derived food samples in Guangdong province from 2015 to 2019. A total of 21 V. cholerae strains were obtained, which exhibited high resistance rates for nalidixic acid (57.14 %, 12/21), ampicillin (33.33 %, 7/21), and ciprofloxacin (19.05 %, 4/21). The quinolone resistance-related gene, qnrVC, was prevalent in 80.95 % (17/21) of the isolates. Additionally, chromosomally mediated quinolone-resistance mutations, including mutations in GyrA at position 83 (S83I) and ParC at position 85 (S85L), were detected in 47.62 % of the isolates. The combination of target mutation and qnrVC genes was shown to mediate resistance or intermediate resistance to ciprofloxacin in V. cholerae. Furthermore, an IncC-type conjugative plasmid carrying thirteen antibiotic resistance genes, including genes conferring resistance to two clinically important antibiotics, cephalosporins and fluoroquinolones, was identified in the shrimp-derived strain Vc516. While none of our food isolates harbored the toxigenic CTX- and TCP-encoding genes, they did possess genes encoding toxins such as HlyA and Autoinducer-2. Notably, some V. cholerae strains from this study exhibited a close genetic relationship with clinical strains, suggesting their potential to cause human infections. Taken together, this study provides a comprehensive view of the epidemiological features and genetic basis of antimicrobial resistance and virulence potential of V. cholerae strains isolated from food in southern China, thereby advancing our understanding of this important pathogen.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Microbiologia de Alimentos , China/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Animais , Humanos , Testes de Sensibilidade Microbiana , Cólera/microbiologia , Cólera/epidemiologia , Vibrio cholerae/genética , Vibrio cholerae/efeitos dos fármacos , Vibrio cholerae/isolamento & purificação , Vibrio cholerae não O1/genética , Vibrio cholerae não O1/efeitos dos fármacos , Vibrio cholerae não O1/isolamento & purificação , Plasmídeos/genética
18.
Eur J Surg Oncol ; 50(6): 108367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38718701

RESUMO

BACKGROUND: The effects of the dynamics of serum tumor markers (CA72-4, CEA, CA19-9, CA125 and AFP) before and after neoadjuvant chemotherapy (NACT) on the prognosis of gastric cancer(GC) patients remain unclear. METHODS: The training set contained 334 GC patients from Fujian Medical University Union Hospital (FJMUUH) and 113 GC patients in Qinghai University Affiliated Hospital (QhUAH) were used as an external validation set. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker- preNACT marker)/preNACT marker]. Tumor marker regression load score (TMRLS) consists of ΔCA72-4, ΔCEA and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic(ROC) curve(AUC), decision curve analysis(DCA), and C-index. RESULTS: Patients from FJMUUH were divided into two groups, TMRLS-low and TMRLS-high, determined by R package maxstat. Survival analysis revealed a higher 3-year overall survival(OS) in the TMRLS-low than in the TMRLS-high group. The TMRLS-high group who received postoperative adjuvant chemotherapy(AC) showed a significantly higher 3-year OS rate than those who did not. Multivariate COX regression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS showed a significantly higher C-index and AUC than the ypTNM stage. The above results were also found in the QhUAH external validation cohort. CONCLUSION: TMRLS is a novel independent prognostic factor for GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, may achieve better survival outcomes. Notably, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.


Assuntos
Antígenos Glicosídicos Associados a Tumores , Biomarcadores Tumorais , Gastrectomia , Terapia Neoadjuvante , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/sangue , Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Ca-125/sangue , Idoso , Antígeno Carcinoembrionário/sangue , Quimioterapia Adjuvante , Antígeno CA-19-9/sangue , Taxa de Sobrevida , Curva ROC , Estudos Retrospectivos , Adulto , alfa-Fetoproteínas
19.
Eur J Med Chem ; 272: 116487, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38759452

RESUMO

Acute lung injury (ALI) and inflammatory bowel disease (IBD) are common inflammatory illnesses that seriously affect people's health. Herein, a series of 4-hydroxylcoumarin (4-HC) derivatives were designed and synthesized. The inhibitory effects of these compounds on LPS-induced interleukin-6 (IL-6) release from J774A.1 cells were then screened via ELISA assay, compound B8 showed 3 times more active than the lead compound 4-HC. The most active compound B8 had the IC50 values of 4.57 µM and 6.51 µM for IL-6 release on mouse cells J774A.1 and human cells THP-1, respectively. Furthermore, we also found that B8 could act on the MAPK pathway. Based on the target prediction results of computer virtual docking, kinase inhibitory assay was carried out, and it revealed that targeting IRAK1 was a key mechanism for B8 to exert anti-inflammatory activity. Moreover, B8 exerted a good therapeutic effect on the dextran sulfate sodium (DSS)-induced colitis model and liposaccharide (LPS)-induced ALI mouse models. The acute toxicity experiments indicated that high-dose B8 caused no adverse reactions in mice, confirming its safety in vivo. Additionally, the preliminary pharmacokinetic (PK) parameters of B8 in SD rats were also examined, revealing a bioavailability (F) of 28.72 %. In conclusion, B8 is a potential candidate of drug for the treatment of ALI and colitis.


Assuntos
4-Hidroxicumarinas , Lesão Pulmonar Aguda , Colite , Desenho de Fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Colite/tratamento farmacológico , Colite/induzido quimicamente , Camundongos , Humanos , Relação Estrutura-Atividade , 4-Hidroxicumarinas/farmacologia , 4-Hidroxicumarinas/química , 4-Hidroxicumarinas/síntese química , Estrutura Molecular , Sulfato de Dextrana , Masculino , Relação Dose-Resposta a Droga , Ratos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Interleucina-6/metabolismo , Interleucina-6/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Linhagem Celular
20.
ACS Omega ; 9(17): 19117-19126, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38708221

RESUMO

Brucea javanica oil emulsion (BJOE) is a compound Chinese medicine used for treating various cancers, such as lung cancer. However, the exact mechanism of its antilung cancer active ingredient remains unclear. This study aims to explore and validate the effective active ingredients and mechanism of action of BJOE in the treatment of lung cancer through network pharmacology, molecular docking technology, and cell experiments. The results showed that there were 13 active ingredients, 136 target genes, and 42 disease target-coexpressed genes in BJOE. The molecular docking results indicated that the main active components of the oil emulsion, YD1 (ß-sitosterol), YD2 (luteolin), and YD3 (bruceitol), could stably bind to TP53 and MAPK1. Furthermore, the commercially available ß-sitosterol luteolin was used as a representative compound to conduct cell experiments to verify its anticancer activity and mechanism. It was found that luteolin can inhibit the proliferation better than ß-sitosterol and the activity of lung cancer cells by regulating the expression of related proteins through the P53/MAPK1 signaling pathway. This study combines network pharmacology prediction with experiments to demonstrate the "multicomponent, multitarget, multipathway" approach of B. javanica oil emulsion in treating lung cancer.

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