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1.
Front Psychiatry ; 15: 1265722, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559394

RESUMO

Objectives: Although sexual minorities have reported higher levels of suicidal ideation than heterosexuals across cultures, the role of various psychosocial factors underlying this disparity among young men has been understudied, particularly in China. This study examined the multiple mediating effects of psychosocial factors between sexual orientation and suicidal ideation in Chinese sexual minority and heterosexual young men. Methods: 302 Chinese cisgender men who identified as gay or bisexual, and 250 cisgender heterosexual men (n=552, aged 18-39 years) completed an online questionnaire measuring perceived social support, self-esteem, depressive symptoms, and suicidal ideation. Results: Young sexual minority men reported significantly higher suicidal ideation and lower social support than their heterosexual peers. Structural equation modelling revealed two multiple indirect pathways. One pathway indicated that sexual orientation was indirectly related to suicidal ideation via family support and depressive symptoms. Another pathway indicated that sexual orientation was indirectly related to suicidal ideation via support from friends, self-esteem, and depressive symptoms. Conclusions: This study is among the first to examine the potentially cascading relationships between sexual orientation and psychosocial factors with suicidal ideation in a Chinese sample of young men. The findings highlight several promising psychosocial targets (i.e., improving family/friend support and increasing self-esteem) for suicide interventions among sexual minority males in China.

2.
bioRxiv ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38559130

RESUMO

A programmed developmental switch to G / S endocycles results in tissue growth through an increase in cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute to cancer. Much remains unknown, however, about how these iECs affect tissue growth. Using the D. melanogasterwing disc as model, we find that populations of iECs initially increase in size but then subsequently undergo a heterogenous arrest that causes severe tissue undergrowth. iECs acquired DNA damage and activated a Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant and not eliminated from the epithelium. Instead, iECs entered a JNK-dependent and reversible senescent-like arrest. Senescent iECs promoted division of diploid neighbors, but this compensatory proliferation did not rescue tissue growth. Our study has uncovered unique attributes of iECs and their effects on tissue growth that have important implications for understanding their roles in wound healing and cancer.

3.
Br J Pharmacol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532634

RESUMO

BACKGROUND AND PURPOSE: The interleukin (IL)-36 pathway is a critical player in the pathogenesis of pustular psoriasis. However, therapies targeting this pathway are limited or unaffordable (e.g. the anti-IL-36 receptor antibody). AMP-activated protein kinase (AMPK), a regulator of cellular energy and metabolism, is known to participate in inflammatory diseases. However, its role in IL-36-induced skin inflammation remains unclear. Therefore, we sought to investigate the role of AMPK signals in regulating IL-36-induced responses in the skin. EXPERIMENTAL APPROACH: IL-36-stimulated primary normal human epidermal keratinocytes (NHEKs) and IL-36-injected (intradermally) BALB/c mice served as the cell and animal models, respectively. Additionally, 5-aminoimidazole-4-carboxamide riboside (AICAR) and A769662 served as AMPK activators. KEY RESULTS: AICAR and A769662 significantly suppressed the IL-36-induced IL-8 (CXCL8) and CCL20 production from NHEKs. IL-36-induced IκBζ protein expression was prominently reduced and IKK/IκBα phosphorylation was attenuated by AICAR and A769662. Conversely, AMPKα knockdown increased IκBζ protein expression and IKK/IκBα phosphorylation in IL-36-treated NHEKs. Furthermore, AICAR and A769662 enhanced IL-36-induced-IκBζ protein degradation via the proteasome-dependent but not the lysosome-dependent pathway. Pretreatment of NHEKs with IL-36 slightly suppressed the AICAR- and A769662-triggered phosphorylation of AMPK and acetyl-CoA carboxylase. In the mouse model, topical application of AICAR significantly reduced ear swelling, redness, epidermal thickening, neutrophil infiltration and inflammatory and antimicrobial peptide gene expression. CONCLUSION AND IMPLICATIONS: AMPK activation suppresses IL-36-induced IL-8 and CCL20 release by regulating IκBζ expression in keratinocytes and reduces IL-36-induced skin inflammation in mice, suggesting that AMPK activation is a potential strategy for treating patients with IL-36-mediated inflammatory skin disorders.

4.
Materials (Basel) ; 17(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38541499

RESUMO

The use of biobased flame-retardant (FR) agents for reducing the flammability of polyester/cotton (T/C) blend fabrics is highly desirable. In this study, a novel and sustainable phosphorus/nitrogen-containing FR, namely, phytic acid-urea (PA-UR) salt, was synthesized. The PA-UR salt was further used to enhance the FR performance of T/C fabric through surface modification. We further explored the potential chemical structure of PA-UR and the surface morphology, thermal stability, heat release capacity, FR properties, and mode of action of the coated fabric. The coated fabric achieved self-extinguishing and exhibited an increased limiting oxygen index of 31.8%. Moreover, the coated T/C blend fabric demonstrated a significantly reduced heat release capacity, indicating a decreased fire hazard. Thermogravimetric analysis revealed the anticipated decomposition of the coated T/C blend fabric and a subsequent increase in thermal stability. The burned char residues also maintained their fiber shape structures, suggesting the presence of condensed FR actions in the PA-UR-coated T/C blend fabric.

5.
J Exp Clin Cancer Res ; 43(1): 65, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424547

RESUMO

BACKGROUND: Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach. METHODS: In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing to identify novel cancer-associated variants. Subsequently, these variants were validated in a 222 cancer patient cohort, and CGN c.3560C > T was identified as a potential cancer-risk allele. Both wild-type (WT) (c.3560C > C) and variant (c.3560C > T) were transfected into cancer cell lines and incorporated into orthotopic xenograft mice model for evaluating their effects on cancer progression. Western blot, immunofluorescence analysis, migration and invasion assays, two-dimensional gel electrophoresis with mass spectrometry, immunoprecipitation assays, and siRNA applications were used to explore the biological consequence of CGN c.3560C > T. RESULTS: In cancer cell lines and orthotopic animal models, CGN c.3560C > T enhanced tumor progression with reduced sensitivity to oxaliplatin compared to the CGN WT. The variant induced downregulation of epithelial marker, upregulation of mesenchymal marker and transcription factor, which converged to initiate epithelial-mesenchymal transition (EMT). Proteomic analysis was conducted to investigate the elements driving EMT in CGN c.3560C > T. This exploration unveiled overexpression of IQGAP1 induced by the variant, contrasting the levels observed in CGN WT. Immunoprecipitation assay confirmed a direct interaction between CGN and IQGAP1. IQGAP1 functions as a regulator of multiple GTPases, particularly the Rho family. This overexpressed IQGAP1 was consistently associated with the activation of Rac1, as evidenced by the analysis of the cancer cell line and clinical sample harboring CGN c.3560C > T. Notably, activated Rac1 was suppressed following the downregulation of IQGAP1 by siRNA. Treatment with NSC23766, a selective inhibitor for Rac1-GEF interaction, resulted in the inactivation of Rac1. This intervention mitigated the EMT program in cancer cells carrying CGN c.3560C > T. Consistently, xenograft tumors with WT CGN showed no sensitivity to NSC23766 treatment, but NSC23766 demonstrated the capacity to attenuate tumor growth harboring c.3560C > T. CONCLUSIONS: CGN c.3560C > T leads to IQGAP1 overexpression, subsequently triggering Rac1-dependent EMT. Targeting activated Rac1 is a strategy to impede the advancement of cancers carrying this specific variant.


Assuntos
Neoplasias , Proteínas de Junções Íntimas , Animais , Humanos , Camundongos , Movimento Celular , Proteínas do Citoesqueleto/metabolismo , Transição Epitelial-Mesenquimal/genética , Neoplasias/genética , Proteômica , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , RNA Interferente Pequeno/farmacologia , Proteínas de Junções Íntimas/metabolismo
6.
J Med Virol ; 96(3): e29426, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38420851

RESUMO

With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.


Assuntos
Infecções por Papillomavirus , Médicos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Papillomavirus Humano , Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Manejo de Espécimes/métodos , Esfregaço Vaginal/métodos , Sensibilidade e Especificidade
7.
Laryngoscope Investig Otolaryngol ; 9(1): e1216, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38362177

RESUMO

Objective: Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare malignancy with various treatment strategies and outcomes. The purpose of this study was to evaluate the clinical characteristics and survival outcomes and identify prognostic factors in patients with SCC of EAC. Methods: Twenty-one patients with SCC of EAC treated in a single tertiary center between 2009 and 2021 were retrospectively reviewed and analyzed. The modified Pittsburgh classification system was applied for staging. Factors associated with survival were identified by univariate survival analysis. Results: The mean age at diagnosis was 61 years (range: 41-79 years). Early-stage (T1 + T2) accounts for 38.1% of the series and advanced-stage (T3 + T4) accounts for 61.9%. Eighteen (85.7%) patients underwent primary surgery with curative intent. The 5-year overall survival rate of the 21 patients was 67.4%. Tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura were associated with poor prognosis in univariate analysis (p = .046; .008; .027; and .08, respectively). Conclusions: Factors predictive of less favorable survival include the history of COM, tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura. It is important to make a precise and systemic preoperative evaluation of disease extent. Level of Evidence: 4.

8.
Talanta ; 270: 125611, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38181598

RESUMO

A decomposition Mueller matrix method is proposed for detection of miRNA and enhanced by using a surface plasmon resonance (SPR). In the proposed approach, a Mueller matrix decomposition method is employed to extract the linear birefringence (LB) and circular dichroism (CD) properties of the miRNA sample. The accuracy of the LB and CD measurements is enhanced through the use of a high-resolution antimonene-based SPR prism coupler with DNA-linked gold nanoparticles (AuNPs). The feasibility of the proposed method is demonstrated by measuring the LB orientation angle (α) and CD property (R) of two miRNA aqueous solutions (hsa-miR-125-5p and hsa-miR-21-5p) over the concentration range of 0∼1000 fM in both cases. The results show that, for both samples, α and R vary linearly with the change in the miRNA concentration. Furthermore, the values of α and R obtained for the two samples are quantifiably different, and hence the selectivity of the proposed SPR sensor is confirmed. Overall, the results highlight the potential of the proposed sensor as a valuable tool for miRNA detection with prospective applications in cancer diagnosis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Ressonância de Plasmônio de Superfície/métodos , MicroRNAs/genética , Ouro , DNA/genética , Técnicas Biossensoriais/métodos
9.
Environ Toxicol ; 39(3): 1494-1504, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37994244

RESUMO

As a synthetic androgen, 17α-methyltestosterone (MT) is widely used in aquaculture to induce sex reversal and may pose a potential risk to aquatic organisms. This ecological risk has attracted the attention of many scholars, but it is not comprehensive enough. Thus, the adverse effects of MT on zebrafish (Danio rerio) were comprehensively evaluated from gonadal histology, as well as the mRNA expression levels of 47 genes related to hypothalamic-pituitary-gonadal (HPG) axis, germ cell differentiation, sex determination, and hypothalamus-pituitary-thyroid (HPT) axis. Adult zebrafish with a female/male ratio of 5:7 were exposed to a solvent control (0.001% dimethyl sulfoxide) and three measured concentrations of MT (5, 51 and 583 ng/L) for 50 days. The results showed that MT had no significant histological effects on the ovaries of females, but the frequency of late-mature oocytes (LMO) showed a downward trend, indicating that MT could induce ovarian suppression to a certain extent. The transcriptional expression of activating transcription factor 4b1 (atf4b1), activating transcription factor 4b2 (atf4b2), calcium/calmodulin-dependent protein kinase II delta 1 (camk2d1), calcium/calmodulin-dependent protein kinase II delta 2 (camk2d2) and calcium/calmodulin-dependent protein kinase II inhibitor 2 (camk2n2) genes in the brain of females increased significantly at all treatment groups of MT, and the mRNA expression of forkhead box L2a (foxl2) and ovarian cytochrome P450 aromatase (cyp19a1a) genes in the ovaries were down-regulated by 5 and 583 ng/L group, which would translate into inhibition of oocyte development. As compared to females, MT had relatively little effects on the reproductive system of males, and only the transcriptional alterations of synaptonemal complex protein 3 (sycp3) and 17-alpha-hydroxylase/17,20-lyase (cyp17) genes were observed in the testes, not enough to affect testicular histology. In addition, MT at all treatments strongly increased corticotropin-releasing hormone (crh) transcript in the brain of females, as well as deiodinase 2 (dio2) transcript in the brain of males. The paired box protein 8 (pax8) gene was significantly decreased at 51 or 583 ng/L of MT in both female and male brains. The above results suggest that MT can pose potential adverse effects on the reproductive and thyroid endocrine system of fish.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Masculino , Feminino , Peixe-Zebra/metabolismo , Metiltestosterona/metabolismo , Metiltestosterona/farmacologia , Eixo Hipotalâmico-Hipofisário-Gonadal , Glândula Tireoide/metabolismo , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Gônadas , Expressão Gênica , Células Germinativas , RNA Mensageiro/metabolismo , Fatores Ativadores da Transcrição/genética , Fatores Ativadores da Transcrição/metabolismo , Fatores Ativadores da Transcrição/farmacologia , Poluentes Químicos da Água/metabolismo
10.
J Formos Med Assoc ; 123(1): 7-15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37690868

RESUMO

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico , Melanoma/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/genética , Taiwan , Imunoterapia , Consenso
11.
J Environ Manage ; 351: 119937, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159304

RESUMO

Petroleum hydrocarbon (PHC) degrading bacteria have been frequently discovered. However, in practical application, a single species of PHC degrading bacterium with weak competitiveness may face environmental pressure and competitive exclusion due to the interspecific competition between petroleum-degrading bacteria as well as indigenous microbiota in soil, leading to a reduced efficacy or even malfunction. In this study, the diesel degradation ability and environmental robustness of an endophytic strain Pseudomonas aeruginosa WS02, were investigated. The results show that the cell membrane surface of WS02 was highly hydrophobic, and the strain secreted glycolipid surfactants. Genetic analysis results revealed that WS02 contained multiple metabolic systems and PHC degradation-related genes, indicating that this strain theoretically possesses the capability of oxidizing both alkanes and aromatic hydrocarbons. Gene annotation also showed many targets which coded for heavy metal resistant and metal transporter proteins. The gene annotation-based inference was confirmed by the experimental results: GC-MS analysis revealed that short chain PHCs (C10-C14) were completely degraded, and the degradation of PHCs ranging from C15-C22 were above 90% after 14 d in diesel-exposed culture; Heavy metal (Mn2+, Pb2+ and Zn2+) exposure was found to affect the growth of WS02 to some extent, but not its ability to degrade diesel, and the degradation efficiency was still maintained at 39-59%. WS02 also showed a environmental robustness along with PHC-degradation performance in the co-culture system with other bacterial strains as well as in the co-cultured system with the indigenous microbiota in soil fluid extracted from a PHC-contaminated site. It can be concluded that the broad-spectrum diesel degradation efficacy and great environmental robustness give P. aeruginosa WS02 great potential for application in the remediation of PHC-contaminated soil.


Assuntos
Metais Pesados , Petróleo , Poluentes do Solo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Biodegradação Ambiental , Poluentes do Solo/análise , Petróleo/análise , Hidrocarbonetos/metabolismo , Bactérias/metabolismo , Solo/química , Metais Pesados/análise , Microbiologia do Solo
12.
Semin Cell Dev Biol ; 156: 35-43, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-37331841

RESUMO

One of the important functions of regulated cell death is to prevent cells from inappropriately acquiring extra copies of their genome, a state known as polyploidy. Apoptosis is the primary cell death mechanism that prevents polyploidy, and defects in this apoptotic response can result in polyploid cells whose subsequent error-prone chromosome segregation are a major contributor to genome instability and cancer progression. Conversely, some cells actively repress apoptosis to become polyploid as part of normal development or regeneration. Thus, although apoptosis prevents polyploidy, the polyploid state can actively repress apoptosis. In this review, we discuss progress in understanding the antagonistic relationship between apoptosis and polyploidy in development and cancer. Despite recent advances, a key conclusion is that much remains unknown about the mechanisms that link apoptosis to polyploid cell cycles. We suggest that drawing parallels between the regulation of apoptosis in development and cancer could help to fill this knowledge gap and lead to more effective therapies.


Assuntos
Neoplasias , Poliploidia , Humanos , Neoplasias/genética , Apoptose/genética , Segregação de Cromossomos , Instabilidade Genômica
13.
Small Methods ; : e2301121, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009766

RESUMO

3D printing is now recognized as a significant tool for medical research and clinical practice, leading to the emergence of medical 3D printing technology. It is essential to improve the properties of 3D-printed products to meet the demand for medical use. The core of generating qualified 3D printing products is to develop advanced materials and processes. Taking advantage of nanomaterials with tunable and distinct physical, chemical, and biological properties, integrating nanotechnology into 3D printing creates new opportunities for advancing medical 3D printing field. Recently, some attempts are made to improve medical 3D printing through nanotechnology, providing new insights into developing advanced medical 3D printing technology. With high-resolution 3D printing technology, nano-structures can be directly fabricated for medical applications. Incorporating nanomaterials into the 3D printing material system can improve the properties of the 3D-printed medical products. At the same time, nanomaterials can be used to expand novel medical 3D printing technologies. This review introduced the strategies and progresses of improving medical 3D printing through nanotechnology and discussed challenges in clinical translation.

14.
JPRAS Open ; 38: 237-248, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38021323

RESUMO

Background: The majority of English literature has reported on the somewhat conflicted outcomes of the effect of radiotherapy on immediate breast reconstruction. However, data specifically related to patients of Asian descent has been scarce. This retrospective study aims to shed light on this topic to aid in the management of this group of patients. Methods: All patients who received immediate free perforator flap-based breast reconstruction under a single surgeon over a 10-year period were included in the study. Patient characteristics, oncological and surgical data were collected. Patients were divided into post-mastectomy radiotherapy (PMRT) and non-PMRT groups. The final aesthetic outcome was assessed by a surgeon-reported outcome questionnaire. Patient satisfaction and psychological outcomes were assessed using validated patient-reported outcome (PRO) questionnaire (BREAST-Q), breast reconstruction, and postoperative module. Results: A total of 101 women, with an average age of 44.7 ± 8.4 underwent perforator flap-based reconstruction. Fifteen patients received PMRT, with remaining 86 patients in the non-PMRT group. The mean duration of follow-up was over 5 years (p = 0.514). The recurrence rate was acceptable in the PMRT group (3/15, p = 0.129). There were no significant differences in complication rates between the two groups (p = 1.000). The aesthetic outcomes were comparable (p = 0.342). PRO appears to be lower in the PMRT group. Conclusions: Immediate breast reconstruction with PMRT in the local patient cohort is oncologically safe, acceptable complication profile, revision rate, and aesthetic outcome. PRO showed lower scores in several categories, which differ from normative data generated in the Western population. Further studies will need to examine the confounding effects of radiation in this specific population.

15.
Acta Neurol Taiwan ; 32(3): 108-112, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37674421

RESUMO

PURPOSE: Warfarin is associated with paradoxical procoagulant effect that leads to a transient hypercoagulable state and acute ischemic stroke (AIS). This clinical dilemma is further confounded when the patient has multiple comorbidities and the optimal treatment strategies are unclear. CASE REPORT: We report a 78-year-old male with valvular heart disease, congestive heart failure, and atrial fibrillation, who received bioprosthetic valve replacement and developed AIS related to the paradoxical procoagulant effect of warfarin. Emergent cerebral angiography with mechanical thrombectomy was performed, and recanalization was successfully achieved. After shifting warfarin to nonvitamin K oral anticoagulant (NOAC), the paradoxical procoagulant effect ameliorated. CONCLUSION: This report describes the roles of endovascular therapy and NOAC in patients with similar highly complex conditions and has clinical relevance for therapeutic plans in the clinical setting.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Masculino , Humanos , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Varfarina/efeitos adversos , Anticoagulantes/efeitos adversos , Trombectomia/efeitos adversos
16.
Cell Commun Signal ; 21(1): 233, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723552

RESUMO

Cancer immunotherapy has been proven to be clinically effective in multiple types of cancers. Lymphocyte function-associated antigen 1 (LFA-1), a member of the integrin family of adhesion molecules, is expressed mainly on αß T cells. LFA-1 is associated with tumor immune responses, but its exact mechanism remains unknown. Here, two kinds of mice tumor model of LFA-1 knockout (LFA-1-/-) mice bearing subcutaneous tumor and Apc Min/+;LFA-1-/- mice were used to confirm that LFA-1 knockout resulted in inhibition of tumor growth. Furthermore, it also demonstrated that the numbers of regulatory T cells (Treg cells) in the spleen, blood, mesenteric lymph nodes were decreased in LFA-1-/- mice, and the numbers of Treg cells in mesenteric lymph nodes were also decreased in Apc Min/+;LFA-1-/- mice compared with Apc Min/+ mice. LFA-1 inhibitor (BIRT377) was administered to subcutaneous tumor-bearing LFA-1+/+ mice, and the results showed that the tumor growth was inhibited and the number of Treg cells was reduced. The analysis of TIMER tumor database indicated that LFA-1 expression is positively associated with Treg cells and TNM stage. Conclusively, this suggests that LFA-1 knockout would inhibit tumor growth and is correlated with Treg cells. LFA-1 may be one potential target for cancer immunotherapy. Video Abstract.


Assuntos
Antígeno-1 Associado à Função Linfocitária , Neoplasias , Animais , Camundongos , Linfócitos T Reguladores , Baço , Bases de Dados Factuais
17.
Drug Saf ; 46(10): 975-989, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37776421

RESUMO

BACKGROUND AND OBJECTIVE: Substandard medicines can lead to serious safety issues affecting public health; however, the nature of such issues can be widely heterogeneous. Health product regulators seek to prioritise critical product quality defects for review to ensure that prompt risk mitigation measures are taken. This study aims to classify the nature of issues for substandard medicines using machine learning to augment a risk-based and timely review of cases. METHODS: A combined machine learning algorithm with a keyword-based model was developed to classify quality issues using text relating to substandard medicines (CISTERM). The nature of issues for product defect cases were classified based on Medical Dictionary for Regulatory Activities-Health Sciences Authority (MedDRA-HSA) lowest-level terms. RESULTS: Product defect cases received from January 2010 to December 2021 were used for training (n = 11,082) and for testing (n = 2771). The machine learning model achieved a good recall (precision) of 92% (96%) for 'Product adulterated and/or contains prohibited substance', 86% (90%) for 'Out of specification or out of trend test result' and 90% (91%) for 'Manufacturing non-compliance'. CONCLUSION: Post-market surveillance of substandard medicines remains a key activity for drug regulatory authorities. A combined machine learning algorithm with keyword-based model can help to prioritise the review of product quality defect issues in a timely manner.


Assuntos
Medicamentos Fora do Padrão , Humanos , Aprendizado de Máquina , Algoritmos , Contaminação de Medicamentos , Saúde Pública
18.
Polymers (Basel) ; 15(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37631495

RESUMO

Flexible electrochemical supercapacitors (FESCs) are emerging as innovative energy storage systems, characterized by their stable performance, long cycle life, and portability/foldability. Crucial components of FESCs, such as electrodes and efficient electrolytes, have become the focus of extensive research. Herein, we examine deep eutectic solvent (DES)-based polymer gel systems for their cost-effective accessibility, simple synthesis, excellent biocompatibility, and exceptional thermal and electrochemical stability. We used a mixture a DES, LiClO4-2-Oxazolidinone as the electroactive species, and a polymer, either polyvinyl alcohol (PVA) or polyacrylamide (PAAM) as a redox additive/plasticizer. This combination facilitates a unique ion-transport process, enhancing the overall electrochemical performance of the polymer gel electrolyte. We manufactured and used LiClO4-2-Oxazolidinone (LO), polyvinyl alcohol-LiClO4-2-Oxazolidinone (PVA-LO), and polyacrylamide-LiClO4-2-Oxazolidinone (PAAM-LO) electrolytes to synthesize an MnO2 symmetric FESC. To evaluate their performance, we analyzed the MnO2 symmetric FESC using various electrolytes with cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS). The FESC featuring the PVA-LO electrolyte demonstrated superior electrochemical and mechanical performances. This solid-state MnO2 symmetric FESC exhibited a specific capacitance of 121.6 F/g within a potential window of 2.4 V. Due to the excellent ionic conductivity and the wide electrochemical operating voltage range of the PVA-LO electrolyte, a high energy density of 97.3 Wh/kg at 1200 W/kg, and a long-lasting energy storage system (89.7% capacitance retention after 5000 cycles of GCD at 2 A/g) are feasibly achieved. For practical applications, we employed the MnO2 symmetric FESCs with the PVA-LO electrolyte to power a digital watch and a light-emitting diode, further demonstrating their real-world utility.

19.
Taiwan J Obstet Gynecol ; 62(4): 553-558, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37407193

RESUMO

OBJECTIVE: To evaluate the regression rate of endometrial polyps (EPs) in a cohort of asymmetric women after conservative follow-up. MATERIALS AND METHODS: In this retrospective cohort study, a total of 1006 women with asymptomatic EPs were treated with expectant management or hormonal drugs between June 1999 and May 2018. Four hundred forty-eight women (44.5%) were administered with hormonal medications and 558 women were managed expectantly (55.5%). Office hysteroscopy was performed to confirm the diagnosis and regression of EPs. Hormonal administration included oral contraceptives, progestin and cyclic estrogen/progestin regimen according to physicians' preferences. Clinical characteristics, including the patient's age, body mass index, parity, and type of conservative management were collected. RESULTS: The mean observation time was 14.1 ± 18.5 months (range, 1-162 months). The overall regression rate of EPs in this cohort was 33.5%, 24.6% occurred after medication and 8.9% after expectant management. Patient age (<50 years) (p < 0.001), follow-up period (p = 0.005) and hormonal drugs used (p < 0.001) were significantly associated with EP regression. Twenty-four (7.1%) of the 337 EP regression patients later developed recurrent disease. Follow-up period (p < 0.001) and hormonal drugs used (p = 0.032) were closely related to polyp recurrence after initial regression. Nevertheless, multivariate logistic regression analysis revealed that hormonal drugs used was significantly associated with the regression (p < 0.001) and recurrence (p = 0.016) of EPs. CONCLUSION: Women aged 50 or less are more suitable for conservative treatment for EPs. Hormonal drugs used could increase the incidence of EP regression.


Assuntos
Neoplasias do Endométrio , Pólipos , Neoplasias Uterinas , Gravidez , Humanos , Feminino , Tratamento Conservador , Progestinas/uso terapêutico , Estudos Retrospectivos , Neoplasias Uterinas/complicações , Histeroscopia , Pólipos/terapia , Pólipos/diagnóstico , Neoplasias do Endométrio/diagnóstico
20.
Front Mol Neurosci ; 16: 1160006, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333617

RESUMO

Background: Previous studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis. Methods: 70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds. Results: 59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days. Conclusion: Our findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine.Clinical Trial Registration: http://www.chictr.org.cn/hvshowproject.aspx?id=11101, identifier ChiCTR-INR-17010559.

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