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1.
Anal Chem ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822787

RESUMO

MicroRNA (miRNA) and apurinic/apyrimidinic endonuclease 1 (APE1) have been reported to be closely associated with cancers, making them potential crucial biomarkers and therapeutic targets. However, focusing on the detection of a single target is not conducive to the diagnosis and prognosis assessment of diseases. In this study, an AND logic-gate-based dual-locking hairpin-mediated catalytic hairpin assembly (DL-CHA) was developed for sensitive and specific detection of microRNA and APE1. By addition of a lock to each of the hairpins, with APE1 and microRNA serving as keys, fluorescence signals could only be detected in the presence of simultaneous stimulation by APE1 and miRNA-224. This indicated that the biosensor could operate as an AND logic gate. DL-CHA exhibited advantages such as a low background, rapid response, and high logic capability. Therefore, the biosensor serves as a novel approach to cancer diagnosis with significant potential applications.

2.
Discov Oncol ; 15(1): 160, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735911

RESUMO

BACKGROUND: A greater emphasis has been placed on the part of cell cycle progression (CCP) in cancer in recent years. Nevertheless, the precise connection between CCP-related genes and bladder cancer (BCa) has remained elusive. This study endeavors to establish and validate a reliable risk model incorporating CCP-related factors, aiming to predict both the prognosis and immune landscape of BCa. METHODS: Clinical information and RNA sequencing data were collected from the GEO and TCGA databases. Univariate and multivariate Cox regression analyses were conducted to construct a risk model associated with CCP. The performance of the model was assessed using ROC and Kaplan-Meier survival analyses. Functional enrichment analysis was employed to investigate potential cellular functions and signaling pathways. The immune landscape was characterized using CIBERSORT algorithms. Integration of the risk model with various clinical variables led to the development of a nomogram. RESULTS: To build the risk model, three CCP-related genes (RAD54B, KPNA2, and TPM1) were carefully chosen. ROC and Kaplan-Meier survival analysis confirm that our model has good performance. About immunological infiltration, the high-risk group showed decreased levels of regulatory T cells and dendritic cells coupled with increased levels of activated CD4 + memory T cells, M2 macrophages, and neutrophils. Furthermore, the nomogram showed impressive predictive power for OS at 1, 3, and 5 years. CONCLUSION: This study provides new insights into the association between the CCP-related risk model and the prognosis of BCa, as well as its impact on the immune landscape.

3.
Front Immunol ; 15: 1360132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707908

RESUMO

Introduction: Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. Materials and Methods: Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. Results: The IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. Conclusion: This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.


Assuntos
Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Estenose Espinal , Humanos , Microbioma Gastrointestinal/genética , Estenose Espinal/genética , Estenose Espinal/microbiologia , Predisposição Genética para Doença
4.
Appl Nurs Res ; 77: 151789, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38796252

RESUMO

OBJECTIVE: To understand the relationship between the need for continuing care services and influencing factors, social support, readiness for discharge among discharged pulmonary tuberculosis (PTB) patients. METHODS: A cross-sectional study was conducted among 170 patients from a database of discharged patients with PTB from September 2023 to January 2024. A demographic and disease characteristics questionnaire, continuing care services basic modality questionnaire, continuing care services need questionnaire, the Social Support Rating Scale (SSRS), and the Readiness for Hospital Discharge Scale (RHDS) were used for this investigation. Univariate analysis and multiple linear regression analysis were used to analyze the associated factors. RESULTS: The mean total score for the need for continuing care services among patients with PTB discharged from the hospital was (121.61 ± 22.98). The dimension with the highest score was health education guidance need. Compared to the the original hospital medical personnel, the primary source of care information after discharge was the local medical institutions was statistically significant and negatively correlated with continuing care service need (P = 0.005). Social support was positively associated with need for continuing care services (P = 0.042). CONCLUSION: Discharged PTB patients had a high degree of continuing care service need. Factors influencing the need for continuing care services are the primary source of care information after discharge was the local medical institutions, the social support. Medical staff need to provide targeted continuing care services based on relevant influencing factors to meet the discharge needs of patients.


Assuntos
Alta do Paciente , Apoio Social , Tuberculose Pulmonar , Humanos , Estudos Transversais , Alta do Paciente/estatística & dados numéricos , Feminino , Masculino , China , Pessoa de Meia-Idade , Adulto , Tuberculose Pulmonar/psicologia , Inquéritos e Questionários , Idoso , Continuidade da Assistência ao Paciente/estatística & dados numéricos
5.
Langmuir ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804669

RESUMO

Developing inexpensive, efficient, and stable catalysts is crucial for reducing the cost of electrolytic hydrogen production. Recently, polyoxometalates (POMs) have gained attention and widespread use due to their excellent electrocatalytic properties. This study designed and synthesized three composite materials, NF/PMonW12-n, by using phosphomolybdic-tungstic heteropolyacids as precursors to grow in situ on nickel foam via the hydrothermal process and subsequent calcination. Then, their catalytic performances are systematically investigated. This work demonstrates that the NF/PMonW12-n catalysts generate more low valent oxides under the synergistic effect of Mo and W, further enhancing activity for hydrogen evolution reaction (HER). Among these electrocatalysts, NF/PMo6W6 exhibits the perfect HER performance, η10 is only 74 mV. It also shows great stability during long-term electrolysis. The current study introduces a fresh approach for producing electrocatalysts that are both cost-effective and highly efficient.

6.
Risk Manag Healthc Policy ; 17: 1239-1251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38765781

RESUMO

Introduction: Traditional Chinese medicine (TCM) holds great potential in promoting healing and relieving pain for herpes zoster (HZ) treatments. Evidence showed that both healthcare professionals' (HCPs) belief and knowledge influence their attitudes, which result in their expression and direct behavior. However, little is known in this area regarding TCM treatments for HZ. This study aimed to understand the HCPs' perceptions, attitudes, beliefs, and practices toward TCM and its services for HZ. Methods: During July 2021 and October 2022, a cross-sectional study of HCPs querying demographics, perceptions, attitudes, beliefs, and practices toward TCM and TCM services for HZ was conducted. The frequency and percentage or mean and standard deviation were used to present categorical data and continuous data, respectively. A Chi-square analysis compared nurses' and doctors' views on TCM treatments for HZ. Results: Out of 306 eligible respondents, 66.0% used TCM content in clinical practice less than 40% of the time. Respondents reported that there were three main advantages of TCM for HZ, including better crusting and healing, fewer side effects, and mitigating complications. A total of 41.3% (81/196) of the respondents who had cared for/treated HZ patients applied TCM treatments. The three factors most associated with referrals/providing TCM to patients were postherpetic neuralgia, early erythema or papules, and acute pain. Compared to nurses, doctors showed more endorsement of the efficacy and cost-effectiveness of TCM treatments for HZ patients. Conclusion: The study found that most healthcare professionals in HZ had a favorable view of TCM, but lacked practical experience administering it to patients. Programs should be developed to provide evidence-based TCM treatments and encourage combining TCM with Western medicine for better patient care.

7.
Exp Gerontol ; 192: 112452, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38718888

RESUMO

Ischemic stroke rapidly increases the expression level of vascular endothelial growth factor (VEGF), which promotes neovascularization during hypoxia. However, the effect and mechanism of VEGF intervention on cerebrovascular formation remain unclear. Therefore, our research discussed the protective effect of exogenous VEGF on cells in hypoxia environment in cerebral microvascular endothelial cells, simulating ischemic stroke in hypoxic environment. Firstly, we detected the proliferation and apoptosis of cerebral microvascular endothelial cells under hypoxia environment, as well the expression levels of VEGF-E, vascular endothelial growth factor re-ceptor-2 (VEGFR-2), BCL2, PRKCE and PINK1. Moreover, immunofluorescence and western blotting were used to verify the regulation of exogenous VEGF-E on VEGFR-2 expression in hypoxic or normal oxygen environment. Lastly, we manipulated the concentration of VEGF-E in the culture medium to investigate its impact on phospholipase Cγ1 (PLCγ1)/extracellular signaling regulatory protein kinase (ERK) -1/2 and protein kinase B (AKT) pathways. Additionally, we employed a PLCγ1 inhibitor (U73122) to investigate its impact on proliferation and PLCγ1/ERK pathways. The results show that hypoxia inhibited the proliferation of cerebral microvascular endothelial cells, promoted cell apoptosis, significantly up-regulated the expression of VEGF-E, VEGFR-2, PRKCE and PINK1, but down-regulated the expression of BCL2. Interference from exogenous VEGF-E activated PLCγ1/ERK-1/2 and AKT pathways, promoting cell proliferation and inhibiting apoptosis of hypoxic brain microvascular endothelial cells. In summary, exogenous VEGF-E prevents hypoxia-induced damage to cerebral microvascular endothelial cells by activating the PLCγ1/ERK and AKT pathways. This action inhibits the apoptosis pathway in hypoxic cerebral microvascular endothelial cells, thereby safeguarding the blood-brain barrier and the nervous system.


Assuntos
Apoptose , Hipóxia Celular , Células Endoteliais , Fosfolipase C gama , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Fosfolipase C gama/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Encéfalo/irrigação sanguínea , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ratos , Microvasos/efeitos dos fármacos , Células Cultivadas , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia
8.
Medicine (Baltimore) ; 103(14): e37507, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579070

RESUMO

Interleukin 6 (IL-6), a pleiotropic cytokine, is crucial in a variety of inflammatory and immunological disorders. In recent years, mendelian randomization, which is a widely used and successful method of analyzing causality, has recently been investigated for the relationship between the IL-6 pathway and related diseases. However, no studies have been conducted to review the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization. In this study, the Web of Science Core Collection (WoSCC) served as our literature source database to gather articles about the IL-6 signaling pathway in Mendelian randomization from 2013 to 2023. VOSviewer (version 1.6.18), Microsoft Excel 2021, and Scimago Graphica were employed for bibliometric and visualization analysis. A total of 164 documents that were written by 981 authors coming from 407 institutions across 41 countries and published in 107 journals were located from January 2013 to August 2023. With 64 and 25, respectively, England and the University of Bristol had the highest number of publications. Frontiers in Immunology is the most prolific journal, and Golam M Khandaker has published the highest number of significant articles. The most co-cited article was an article entitled the interleukin-6 receptor as a target for prevention of coronary-heart-disease: a Mendelian randomization analysis, written by Daniel I Swerdlow. The most popular keywords were "mendelian randomization," "interleukin-6," "il-6," "c-reactive protein," "association," "coronary-heart-disease," "inflammation," "instruments," "risk," "rheumatoid arthritis," "depression." The full extent of the existing literature over the last 10 years is systematically revealed in this study, which can provide readers with a valuable reference for fully comprehending the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization.


Assuntos
Artrite Reumatoide , Interleucina-6 , Humanos , Bibliometria , Citocinas , Transdução de Sinais
9.
Int J Biol Macromol ; 267(Pt 2): 131487, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599430

RESUMO

Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.


Assuntos
Quitosana , Portadores de Fármacos , Liberação Controlada de Fármacos , Ginsenosídeos , Nanopartículas , Quitosana/química , Quitosana/análogos & derivados , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Ginsenosídeos/farmacocinética , Concentração de Íons de Hidrogênio , Nanopartículas/química , Humanos , Portadores de Fármacos/química , Linhagem Celular Tumoral , Tamanho da Partícula
10.
Sci Total Environ ; 927: 172304, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38604357

RESUMO

Hyperthermophilic composting, characterized by temperatures equal to or exceeding 75 °C, offers superior compost maturity and performance. Inoculation with thermophilic bacteria presents a viable approach to achieving hyperthermophilic composting. This study investigates the effects of inoculating thermophilic bacteria, isolated at different temperatures (50 °C, 60 °C, and 70 °C) into compost on maturity, gaseous emissions, and microbial community dynamics during co-composting. Results indicate that the thermophilic bacteria inoculation treatments exhibited peak temperature on Day 3, with the maximum temperature of 75 °C reached two days earlier than the control treatment. Furthermore, these treatments demonstrated increased bacterial richness and diversity, along with elevated relative abundances of Firmicutes and Proteobacteria. They also fostered mutualistic correlations among microbial species, enhancing network connectivity and complexity, thereby facilitating lignocellulose degradation. Specifically, inoculation with thermophilic bacteria at 60 °C increased the relative abundance of Thermobifida and unclassified-f-Thermomonosporaceae (Actinobacteriota), whereas Bacillus, a thermophilic bacterium, was enriched in the 70 °C inoculation treatment. Consequently, the thermophilic bacteria at 60 °C and 70 °C enhanced maturity by 36 %-50 % and reduced NH3 emissions by 1.08 %-27.50 % through the proliferation of thermophilic heterotrophic ammonia-oxidizing bacteria (Corynebacterium). Moreover, all inoculation treatments decreased CH4 emissions by 6 %-27 % through the enrichment of methanotrophic bacteria (Methylococcaceae) and reduced H2S, Me2S, and Me2SS emissions by 1 %-25 %, 47 %-63 %, and 15 %-53 %, respectively. However, the inoculation treatments led to increased N2O emissions through enhanced denitrification, as evidenced by the enrichment of Truepera and Pusillimonas. Overall, thermophilic bacteria inoculation promoted bacteria associated with compost maturity while attenuating the relationship between core bacteria and gaseous emissions during composting.


Assuntos
Bactérias , Compostagem , Microbiota , Microbiologia do Solo , Compostagem/métodos , Microbiota/fisiologia , Temperatura Alta , Poluentes Atmosféricos/análise
11.
Environ Int ; 185: 108532, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422876

RESUMO

Nanoplastics (NPs) continue to accumulate in global aquatic and terrestrial systems, posing a potential threat to human health through the food chain and/or other pathways. Both in vivo and in vitro studies have confirmed that the liver is one of the main organs targeted for the accumulation of NPs in living organisms. However, whether exposure to NPs induces size-dependent disorders of liver lipid metabolism remains controversial, and the reversibility of NPs-induced hepatotoxicity is largely unknown. In this study, the effects of long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs) on lipid accumulation were investigated in terms of autophagy and lysosomal mechanisms. The findings indicated that hepatic lipid accumulation was more pronounced in mice exposed to 100 nm PS-NPs compared to 500 nm PS-NPs. This effect was effectively alleviated after 50 days of self-recovery for 100 nm and 500 nm PS-NPs exposure. Mechanistically, although PS-NPs exposure activated autophagosome formation through ERK (mitogen-activated protein kinase 1)/mTOR (mechanistic target of rapamycin kinase) signaling pathway, the inhibition of Rab7 (RAB7, member RAS oncogene family), CTSB (cathepsin B), and CTSD (cathepsin D) expression impaired lysosomal function, thereby blocking autophagic flux and contributing to hepatic lipid accumulation. After termination of PS-NPs exposure, lysosomal exocytosis was responsible for the clearance of PS-NPs accumulated in lysosomes. Furthermore, impaired lysosomal function and autophagic flux inhibition were effectively alleviated. This might be the main reason for the alleviation of PS-NPs-induced lipid accumulation after recovery. Collectively, we demonstrate for the first time that lysosomes play a dual role in the persistence and reversibility of hepatotoxicity induced by environmental relevant doses of NPs, which provide novel evidence for the prevention and intervention of liver injury associated with nanoplastics exposure.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Nanopartículas , Poluentes Químicos da Água , Humanos , Animais , Camundongos , Microplásticos , Poliestirenos/toxicidade , Lisossomos , Lipídeos
12.
Skin Res Technol ; 30(2): e13595, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38279591

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common inherited disorder characterized by cutaneous neurofibromas and other features. It is still a challenge in managing inoperable patients and the complex nature of the disease. Bibliometric analyses for cutaneous neurofibromas (cNF) could offer insights into impactful research and collaborations, guiding future efforts to improve patient care and outcomes. METHODS: We conducted a comprehensive literature search of the Web of Science Core Collection database for the period 2003-2022. Data processing and analysis were performed using bibliometric tools including VOSviewer, CiteSpace, and "Bibliometrix" package. Our analysis assessed the publication or collaboration of countries, institutions, authors, and journals, as well as the co-citation and burst of references and keywords. RESULTS: The analysis included 927 articles from 465 journals and 1402 institutions in 67 countries. Research on cNF has been increasing in recent years. The United States leads the field. Pierre Wolkenstein was the top author, while The University of Hamburg was the most productive institution. The American Journal of Medical Genetics Part A published the most articles in cNF. Co-citation analysis revealed major research topics and trends over time, showing growing interest in evaluating quality of life and genotype-phenotype correlation for cNF patients. Emerging topical MEK inhibitors show potential as a promising therapy. CONCLUSION: In conclusion, our bibliometric analysis of cNF research over the past two decades highlights the growing interest in this complex genetic disorder. Leading countries, authors, institutions, and journals have played significant roles in shaping the field. Notably, recent trends emphasize the importance of evaluating quality of life and genotype-phenotype correlations in cNF patients. Furthermore, the emergence of promising topical therapy marks an exciting development in the quest to improve patient care and outcomes for those affected by cNF, paving the way for future research and collaboration.


Assuntos
Neurofibroma , Neoplasias Cutâneas , Humanos , Qualidade de Vida , Bibliometria , Bases de Dados Factuais
13.
Langmuir ; 40(1): 744-750, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38103033

RESUMO

To explore, highly active electrocatalysts are essential for water splitting materials. Polyoxometalates (POMs) have drawn interesting attention in recent years due to their abundant structure and unique electrocatalytic properties. In this study, by using a POM-based precursor Co2Mo10, novel bimetallic sulfide (CoS2-MoS2) nanocomposites are rationally designed and synthesized under hydrothermal conditions. The incorporation of Co2+ to the host electrocatalyst could effectively increase the exposure of active sites of MoS2. Compared to pure MoS2, the CoS2-MoS2 nanocomposite exhibited a perfect hydrogen evolution reaction (HER) ability, for it merely requires overpotentials of 120 and 153 mV for 10 mA cm-2 working current density toward the HER in 1 M KOH and 0.5 M H2SO4 electrolyte systems, respectively. Additionally, the nanocomposite exhibited outstanding chemical stability and long-term durability. This study presents a novel strategy that utilizes POMs to enrich the exposed edge sites of MoS2, resulting in the preparation of efficient electrocatalysts.

14.
BMC Cancer ; 23(1): 1200, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057772

RESUMO

BACKGROUND: The mammalian target of rapamycin (mTOR) kinase, a central component of the PI3K/AKT/mTOR pathway, plays a critical role in tumor biology as an attractive therapeutic target. We conducted this first-in-human study to investigate the safety, pharmacokinetics (PK), and pilot efficacy of LXI-15029, an mTORC1/2 dual inhibitor, in Chinese patients with advanced malignant solid tumors. METHODS: Eligible patients with advanced, unresectable malignant solid tumors after failure of routine therapy or with no standard treatment were enrolled to receive ascending doses (10, 20, 40, 60, 80, 110, and 150 mg) of oral LXI-15029 twice daily (BID) (3 + 3 dose-escalation pattern) until disease progression or intolerable adverse events (AEs). The primary endpoints were safety and tolerability. RESULTS: Between June 2017 and July 2021, a total of 24 patients were enrolled. LXI-15029 was well tolerated at all doses. Only one dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in the 150 mg group, and the maximum tolerated dose was 110 mg BID. The most common treatment-related AEs were leukocytopenia (41.7%), increased alanine aminotransferase (20.8%), increased aspartate aminotransferase (20.8%), prolonged electrocardiogram QT interval (20.8%), and hypertriglyceridemia (20.8%). No other serious treatment-related AEs were reported. LXI-15029 was absorbed rapidly after oral administration. The increases in the peak concentration and the area under the curve were greater than dose proportionality over the dose range. Eight patients had stable disease. The disease control rate was 40.0% (8/20; 95% CI 21.7-60.6). In evaluable patients, the median progression-free survival was 29 days (range 29-141). CONCLUSIONS: LXI-15029 demonstrated reasonable safety and tolerability profiles and encouraging preliminary antitumor activity in Chinese patients with advanced malignant solid tumors, which warranted further validation in phase II trials. TRIAL REGISTRATION: NCT03125746(24/04/2017), http://ClinicalTrials.gov/show/NCT03125746.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Alanina Transaminase , Antineoplásicos/uso terapêutico , População do Leste Asiático , Inibidores Enzimáticos/uso terapêutico , Dose Máxima Tolerável , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases , Serina-Treonina Quinases TOR
15.
Microorganisms ; 11(12)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38137995

RESUMO

As one of the environmental factors that seriously affect plant growth and crop production, drought requires an efficient but environmentally neutral approach to mitigate its harm to plants. Soil microbiomes can interact with plants and soil to improve the adverse effects of drought. Medicago ruthenica (L.) is an excellent legume forage with strong drought tolerance, but the key role of microbes in fighting drought stress remains unclear. What kind of flora plays a key role? Is the recruitment of such flora related to its genotype? Therefore, we selected three varieties of M. ruthenica (L.) for drought treatment, analyzed their growth and development as well as their physiological and biochemical characteristics, and performed 16S rRNA high-throughput sequencing analysis on their rhizosphere soils to clarify the variety-mediated response of rhizosphere bacteria to drought stress. It was found that among the three varieties of M. ruthenica (L.), Mengnong No.2, Mengnong No.1 and Zhilixing were subjected to drought stress and showed a reduction in plant height increment of 24.86%, 34.37%, and 31.97% and in fresh weight of 39.19%, 50.22%, and 41.12%, respectively, whereas dry weight was reduced by 23.26%, 26.10%, and 24.49%, respectively. At the same time, we found that the rhizosphere microbial community of Mengnong No. 2 was also less affected by drought, and it was able to maintain the diversity of rhizosphere soil microflora stable after drought stress, while Mennong No. 1 and Zhilixing were affected by drought stress, resulting in a decrease in rhizosphere soil bacterial community diversity indices to 92.92% and 82.27%, respectively. Moreover, the rhizosphere of Mengnon No. 2 was enriched with more nitrogen-fixing bacteria Rhizobium than the other two varieties of M. ruthenica (L.), which made it still have a good ability to accumulate aboveground biomass after drought stress. In conclusion, this study proves that the enrichment process of bacteria is closely related to plant genotype, and different varieties enrich different types of bacteria in the rhizosphere to help them adapt to drought stress, and the respective effects are quite different. Our results provide new evidence for the study of bacteria to improve the tolerance of plants to drought stress and lay a foundation for the screening and study mechanism of drought-tolerant bacteria in the future.

16.
J Eat Disord ; 11(1): 207, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37986127

RESUMO

BACKGROUND: Bulimia nervosa (BN) is an eating disorder characterized by recurrent binge eating and compensatory behaviors. The thalamus plays a crucial role in the neural circuitry related to eating behavior and needs to be further explored in BN. METHODS: In this study, 49 BN patients and 44 healthy controls (HCs) were recruited. We applied the fractional amplitude of low-frequency fluctuation to investigate regional brain activity in the thalamus and functional connectivity (FC) to examine the synchronization of activity between thalamic subregions and other brain regions in both groups. All results underwent false discovery rate (p < 0.05, FDR correction) correction. Pearson correlation analysis was performed to assess the relationship between the patients' abnormal clinical performance and the thalamic alterations (p < 0.05, FDR correction). RESULTS: We found no significant differences in neural activity between BN patients and HCs in the sixteen thalamic subregions. However, compared to the HCs, the individuals with BN showed decreased FC between the thalamic subregions and several regions, including the bilateral prefrontal cortex, right inferior parietal lobule, right supplementary motor area, right insula, cingulate gyrus and vermis. Additionally, BN patients showed increased FC between the thalamic subregions and visual association regions, primary sensorimotor cortex, and left cerebellum. These altered FC patterns in the thalamus were found to be correlated with clinical variables (the frequency of binge eating/purging per week and external eating behavior scale scores) in the BN group. All results have passed FDR correction. CONCLUSIONS: Our study provides evidence that there is disrupted FC between thalamic subregions and other brain regions in BN patients during resting state. These regions are primarily located within the frontoparietal network, default mode network, somatosensory, and visual network. These findings elucidate the neural activity characteristics underlying BN and suggest that thalamic subregions have potential as targets for future neuromodulation interventions.


The high recurrence rate of bulimia nervosa (BN) poses a clinical challenge, and thus, it is crucial to improve the characterization and identification of brain functional abnormalities as direct targets for novel therapies. To investigate the neural circuitry associated with BN, the thalamus is a critical node since it serves as a higher-order relay point in the cortico-thalamo-cortical information pathway. Our findings reveal that altered functional connectivity (FC) between thalamic nuclei and other brain regions is evident throughout the whole brain, particularly within the frontoparietal network, default mode network, somatosensory, and visual network. These changes in FC are significantly associated with disordered eating behavior and the severity of illness in BN patients. Therefore, these findings help identify the neural mechanisms underlying disordered eating behavior and BN severity and suggest potential targets for future neuromodulation interventions.

17.
BMJ Open ; 13(10): e071745, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37802607

RESUMO

INTRODUCTION: Exposure of pregnant women and newborns to secondhand smoke (SHS) can lead to adverse maternal and neonatal health outcomes. Among expectant and new fathers, who are the main source of SHS exposure for pregnant women, new mothers and babies, smoking rates remain high. A partner's pregnancy potentially constitutes a critical period where expectant and new fathers are motivated to quit smoking. However, there is no consensus on the optimal form and delivery of smoking cessation and relapse-prevention interventions. We present a systematic review and network meta-analysis protocol that aims to synthesise and evaluate the effectiveness of smoking cessation and relapse-prevention interventions tailored for this population. METHODS AND ANALYSIS: To identify relevant studies, we will conduct a comprehensive search, in English and Chinese, of 10 electronic databases. The review will include randomised and quasi-randomised controlled trials that compare behavioural interventions (tailored and non-tailored) with/without the addition of pharmacotherapy with usual care, a minimal or placebo control for assisting expectant and new fathers to quit smoking and prevent smoking relapse. The primary outcome of interest is the self-reported and/or biochemically verified smoking abstinence at ≥1-month follow-up. Two reviewers will independently screen, select and extract relevant studies, and perform a quality assessment. Disagreements will be resolved by a consensus or third-party adjudication. The Cochrane Risk of Bias tool V.2 will be used to assess the risk of bias in the included studies. We will obtain the results of the systematic review through pooled quantitative analyses using a network meta-analysis. Sensitivity and subgroup analyses will be performed. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review of published data. The findings will be disseminated via peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42022340617.


Assuntos
Abandono do Hábito de Fumar , Humanos , Feminino , Recém-Nascido , Gravidez , Masculino , Abandono do Hábito de Fumar/métodos , Metanálise em Rede , Revisões Sistemáticas como Assunto , Gestantes , Pai , Metanálise como Assunto
18.
Quant Imaging Med Surg ; 13(10): 7077-7091, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869275

RESUMO

Background: Accumulating evidence indicates maladaptive neural information interactions between different brain regions underlie bulimia nervosa (BN). However, little is known about the alterations in interhemispheric communication of BN, which is facilitated by the corpus callosum (CC), the major commissural fiber connecting the two hemispheres. To shed light on the interhemispheric communications in BN, the present study aims to explore alterations of interhemispheric homotopic functional connectivity and the CC microstructure in BN. Methods: Based on magnetic resonance imaging (MRI) data collected from 42 BN patients and 38 healthy controls (HCs), the group differences of voxel-mirrored homotopic connectivity (VMHC) index and CC white matter microstructure were compared. Then brain regions with significant group differences in VMHC were selected as seeds for subsequent functional connectivity (FC) analysis. Seed-based fiber tracking and correlation analysis were used to analyze the relationship between VMHC and CC changes. And correlation analysis was used to reveal the correlation between abnormal imaging variables and the clinical features of BN. Results: Compared with HCs, the BN group showed decreased fractional anisotropy (FA) in middle part of CC (CCMid) and increased VMHC in bilateral orbitofrontal cortex (OFC) and middle temporal gyrus (MTG) [false discovery rate (FDR) correction with a corrected threshold of P<0.05]. Subsequent FC analyses indicated increased FC between left OFC and right OFC, bilateral MTG, left middle occipital gyrus and right precuneus (PCUN); between right OFC and left cerebellum crus II and right PCUN; and between left MTG and right inferior temporal gyrus, right cerebellum lobule VI and right medial superior frontal gyrus (FDR correction with a corrected threshold of P<0.05). The VMHC values of OFC and MTG showed no correlations with FA values of the CCMid and the white fibers between the bilateral OFC and MTG were not through the CCMid. In addition, several regions with abnormal FC had a potential correlation trend with abnormal eating behaviors in BN patients (P<0.05, uncorrected). Conclusions: Aberrant interhemispheric homotopic functional connectivity and CC microstructure were observed in BN, and they may be independent of each other. Regions with aberrant interhemispheric homotopic functional connectivity showed hyperconnectivity with regions related to reward processing, body shape perception, and self-reference.

19.
Clin Psychopharmacol Neurosci ; 21(4): 617-633, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37859436

RESUMO

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], -1.61; 95% confidence interval [95% CI], -2.44 to -0.79; p < 0.001), attention deficit hyperactivity disorders (SMD, -0.39; 95% CI, -0.78 to -0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, -0.86; 95% CI, -1.48 to -0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, -0.06; 95% CI, -0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63-0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69-0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

20.
J Clin Neurosci ; 117: 125-135, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37801877

RESUMO

BACKGROUND: To examine serum vitamin B12 concentrations in relation to the risk of ischemic stroke among hospitalized patients in the Department of Neurology. METHODS: We performed a cross-sectional study involving 2,212 inpatients discharged from the Department of Neurology of the First Affiliated Hospital of Chongqing Medical University, from January 2020 to January 2022. The results of laboratory assays such as serum vitamin B12, homocysteine, and folate levels were measured. Logistic regression analysis was used to investigate the association between serum vitamin B12 concentrations and ischemic stroke, with adjustment for a number of relevant demographic and lifestyle factors and comorbidities. RESULTS: A total of 961 (43.4%) patients had an ischemic stroke. In the fully adjusted model, logistic regression analysis suggested a positive association between serum vitamin B12 levels<150 pg/mL (aOR: 1.42; 95% CI 1.02-1.97; p = 0.035), serum vitamin B12 150-300 pg/mL (aOR: 1.37; 95% CI 1.11-1.68; p = 0.003) and the prevalence of ischemic stroke. Furthermore, an inverse association was observed between serum vitamin B12 levels ≥ 900 pg/mL (aOR: 0.38; 95% CI: 0.19-0.77; p =0.007) and the prevalence of ischemic stroke. Moreover, the cut-off value of vitamin B12 concentration was 316.4 pg/mL and the discrimination power of the score evaluated by AUC-ROC was 0.71 (95%CI 0.68-0.73, p<0.001) in the vitamin B12 and ischemic stroke. CONCLUSION: Findings suggest that low vitamin B12 levels may predict the risk of ischemic stroke, early and timely supplementation of vitamin B12 can improve the short-term prognosis of ischemic stroke patients.


Assuntos
AVC Isquêmico , Humanos , Estudos Transversais , Vitamina B 12 , Ácido Fólico , Vitaminas , Homocisteína
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