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1.
Front Public Health ; 12: 1409030, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39148652

RESUMO

Background: Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology. Methods: From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology. Results: In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group. Conclusion: The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.


Assuntos
Papillomavirus Humano , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer , Genótipo , Papillomavirus Humano/genética , Papillomavirus Humano/isolamento & purificação , Estudos Longitudinais , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia
2.
Cornea ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39104013

RESUMO

PURPOSE: To evaluate the corneal biomechanical characteristics of eyes with Sturge-Weber syndrome (SWS) secondary glaucoma (SSG) by analyzing corneal biomechanical parameters obtained using the Corneal Visualization Scheimpflug Technology instrument (Corvis ST). METHODS: In patients with SWS, eyes affected by SSG were designated as the SSG group while the contralateral eyes were designated as the SWS contralateral group (SC group). Patients from the myopia clinic served as the control group. Dynamic corneal response parameters (DCRs) including the stress-strain index (SSI)-a critical material stiffness parameter that excludes interference from IOP and central corneal thickness (CCT)-were analyzed. RESULTS: For CCT, no significant difference was observed between the SSG and SC groups. However, significant differences were found between the SSG and control groups and between the SC and control groups. Parameters such as HC Time, A1 Deformation Amp., A2 Deformation Amp., length of Whole Eye Movement (WEM), DA Ratio Max (2 mm), PachySlope, DA Ratio Max (1 mm), and ARTh showed significant differences between the SSG group and control group. In the SSG group, 4 of night eyes had an SSI of less than 0.85. CONCLUSIONS: Some DCRs indicated a stiffer cornea in the SSG group, possibly due to a thicker cornea in this group. On analyzing SSI, it was found that corneal material properties change, becoming less stiff in some of the patients with SSG. In conclusion, our study provides a preliminary exploration of the biomechanical properties of SWS secondary glaucoma.

3.
Front Pediatr ; 12: 1343162, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39132309

RESUMO

Introduction: The influence of excess weight on the development of children's feet remains a subject of debate. To further elucidate whether this relation occurs, this study compared arch morphology and flexibility in three groups of children: underweight, normal, and overweight. Methods: In total, 1,532 children (807 boys, 725 girls; age range 7-11 years) participated in the study. The researchers measured the participants' height and weight, calculated their body mass index, and categorized their weight status as underweight, normal weight, or overweight. A three-dimensional foot model was taken using a three-dimensional plantar scanner under non-weight-bearing and weight-bearing conditions to obtain arch morphometric indices (arch index and arch volume) and arch flexibility index (arch volume index). Results: Analysis of the data showed that the arch index was higher in overweight children compared to underweight and normal weight children (p < 0.05), but the differences in arch volume and arch volume index in overweight children compared to underweight and normal weight children were not statistically significant (p > 0.05). All children were divided into flatfoot, normal, and pes cavus groups according to arch index, and the arch volume index was statistically significant (p < 0.01). Conclusions: Overweight was not absolutely associated with arch structure and arch flexibility in children from a three-dimensional perspective. Arch development is a long-term process, and it is not clear whether being overweight has an effect on soft tissue or bone formation. Future studies will focus on the effects of long-term overweight on foot structure and arch flexibility in children.

4.
J Environ Manage ; 368: 121992, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137634

RESUMO

Sustaining the development of rural and pastoral communities' hinges on livelihood resilience. Pastoralist household resilience relies on resource availability and decision-making abilities. Despite extensive studies on pastoralist livelihoods, a significant knowledge gap remains in understanding the nuanced adaptive capacities of diverse households, particularly amid grassland degradation. Thus, this study investigates the household-based livelihood resilience of pastoralists in China's Three-River Headwater Region, offering policy recommendations for resilient livelihoods. Using stratified random sampling, 758 pastoralist household heads underwent semi-structured interviews to collect data. Five household characteristics, encompassing age, gender, energy use, well-being perception, and multi-household grazing participation, were evaluated. Looking ot the nature of data, descriptive statistics and non-parametric tests were performed in this study to draw the valid inferences. The results revealed a positive correlation (p < 0.05) between household head age and livelihood resilience, with divergent resilience across age groups. Varied energy usage yielded distinct impacts; households employing solar or mixed energy sources exhibited heightened resilience (p < 0.05). Household well-being emerged as an invariant variable concerning resilience. Furthermore, engagement in multi-household grazing (an informal institution) significantly (p < 0.05) influenced pastoralist livelihood resilience. These insights advocate targeted support for young household heads and the adoption of clean energy. Exploring the deeper strategies and mechanisms of multi-household grazing can enhance understanding and policy integration, guiding eco-friendly progress within rustic landscapes for pastoral communities.

5.
BMC Nurs ; 23(1): 534, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39103791

RESUMO

BACKGROUND: Effective response and reducing the burden of family care for children with cancer is critical, and China currently lacks a specific assessment tool. AIMS: This study aimed to translate and validate the Caregiving Burden Scale for Family Caregivers of Children with Cancer (CBSFC-CC) and then test and implement the tool. METHODS: According to the Beaton cross-cultural debugging guide, preliminary Chinese version of CBSFC-CC scale was formed, which was suitable for Chinese language environment and clinical context. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were performed to verify structural validity. Convergent validity, discriminant validity and reliability were also conducted. RESULTS: A total of 529 family caregivers of children with cancer participated in the survey. EFA extracts and combines four factors and explained 65.80% of the total variation. CFA proved that all the goodness-of-fit indicators were acceptable. The Cronbach's alpha of the Chinese version of CBSFC-CC was .96, and the test-retest reliability coefficient was .95. Four dimensions and 29 items were identified in the final Chinese version of CBSFC-CC. CONCLUSION: The chinese version CBSFC-CC is scientifically reasonable and has good reliability and validity, which can be applied to the investigation of the nursing burden of family caregivers of children with cancer in China.

6.
Clin Kidney J ; 17(8): sfae204, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39099565

RESUMO

Background: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). Methods: The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. Results: In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P < .05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Conclusions: Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.

7.
Front Immunol ; 15: 1407924, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170609

RESUMO

Introduction: Acute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment. Method: To investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment. Result: The analysis discerned 916 differentially expressed genes in moderate/severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators. Discussion: This study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19.


Assuntos
COVID-19 , Ferroptose , Perfilação da Expressão Gênica , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Humanos , Ferroptose/genética , COVID-19/genética , COVID-19/imunologia , Síndrome do Desconforto Respiratório/genética , SARS-CoV-2/fisiologia , Transcriptoma , Redes Reguladoras de Genes , Biologia Computacional/métodos
8.
Bioinformatics ; 40(8)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39107889

RESUMO

MOTIVATION: Transcription factors are pivotal in the regulation of gene expression, and accurate identification of transcription factor binding sites (TFBSs) at high resolution is crucial for understanding the mechanisms underlying gene regulation. The task of identifying TFBSs from DNA sequences is a significant challenge in the field of computational biology today. To address this challenge, a variety of computational approaches have been developed. However, these methods face limitations in their ability to achieve high-resolution identification and often lack interpretability. RESULTS: We propose BertSNR, an interpretable deep learning framework for identifying TFBSs at single-nucleotide resolution. BertSNR integrates sequence-level and token-level information by multi-task learning based on pre-trained DNA language models. Benchmarking comparisons show that our BertSNR outperforms the existing state-of-the-art methods in TFBS predictions. Importantly, we enhanced the interpretability of the model through attentional weight visualization and motif analysis, and discovered the subtle relationship between attention weight and motif. Moreover, BertSNR effectively identifies TFBSs in promoter regions, facilitating the study of intricate gene regulation. AVAILABILITY AND IMPLEMENTATION: The BertSNR source code can be found at https://github.com/lhy0322/BertSNR.


Assuntos
Aprendizado Profundo , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Sítios de Ligação , Biologia Computacional/métodos , DNA/metabolismo , DNA/química , Análise de Sequência de DNA/métodos , Software , Algoritmos
9.
HPB (Oxford) ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39054211

RESUMO

BACKGROUND: To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates. METHODS: Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed. RESULTS: Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival. CONCLUSION: PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement.

10.
Nutr Rev ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39081227

RESUMO

BACKGROUND: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review Guidelines were used to conduct a scoping review of weight loss interventions for patients with prostate cancer, with the goal to ascertain the impact of these interventions on body weight, body composition, metabolic biomarkers, and prostate cancer-related outcomes. METHODS: Six bibliographical databases were searched. Eligible studies included articles reporting weight loss behavioral interventions with at least dietary change as an intervention component, body weight as an outcome, and interventions not solely focused on weight loss maintenance. Patients with prostate cancer of any stage were included. At least 2 independent reviewers used a data-charting form to extract study characteristics and results. RESULTS: A total of 12 studies were included. The sample consisted predominately of White patients with prostate cancer (multiple stages) in the United States. Most interventions included both dietary and physical activity components and were delivered 1-on-1 in-person and/or by telephone. Most of the studies reported that participants experienced significant weight loss and beneficial body composition changes, with a higher proportion of studies with a longer intervention period and dose (time) reporting greater magnitude of changes in outcomes. There were mixed results regarding the interventions' impact on metabolic biomarkers and prostate cancer-related outcomes. DISCUSSION: Understanding the impact of weight loss interventions on patients with prostate cancer is important. Studies including metabolic biomarkers, prostate cancer outcomes, and more diverse populations are needed.

11.
Int J Nanomedicine ; 19: 6677-6692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975322

RESUMO

Background: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration. Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments. Results: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice. Conclusion: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.


Assuntos
Doxorrubicina , Imunoterapia , Polietilenoglicóis , Microambiente Tumoral , Animais , Doxorrubicina/farmacologia , Doxorrubicina/análogos & derivados , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação , Camundongos , Imunoterapia/métodos , Linhagem Celular Tumoral , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Antígeno B7-H1 , Feminino , Humanos , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos BALB C , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Inibidores de Checkpoint Imunológico/farmacologia , Ondas Ultrassônicas , Terapia Combinada
12.
J Health Popul Nutr ; 43(1): 104, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978145

RESUMO

BACKGROUND: After China ended its 'dynamic zero-COVID policy' on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected. METHODS: All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection. RESULTS: A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females [adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07-1.88] and clinical practitioners (aOR: 10.32, 95% CI: 6.57-16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age ≥ 60 years (aOR: 0.30, 95% CI: 0.19-0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23-0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22-0.97 for within 1-3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms. CONCLUSION: Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China's deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , China/epidemiologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Prospectivos , Recursos Humanos em Hospital/estatística & dados numéricos , Inquéritos e Questionários , Incidência , Surtos de Doenças , Fatores de Risco , Vacinas contra COVID-19/administração & dosagem , Adulto Jovem
13.
PeerJ Comput Sci ; 10: e2140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983198

RESUMO

The hiding capacity of the current information hiding field has reached a relatively high level, which can hide two color images into one color image. In order to explore a larger hidden capacity, an information hiding scheme based on an improved FCdDNet is proposed, which can hide large-size color images into small-size color images. An improved FCdDNet network is used as the main structure shared by the hidden network and the extraction network. These two networks promote and improve each other during the confrontation training process and are used in pairs. It can be seen that the proposed scheme achieves a larger information hiding capacity, and the hidden information is four times larger than the scale of the carrier image. At the same time, the visual effect after hiding is guaranteed, and the image extracted from the hidden image also has a high degree of restoration. The scheme can be applied to image authentication, secret image transmission, and other fields.

14.
Malays J Med Sci ; 31(3): 217-228, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38984240

RESUMO

Background: Often, the indirect impact of autism spectrum disorder (ASD) presents the family with significant challenges. One of these challenges is affiliate stigma due to parental affiliation with their child. This study aimed to explore affiliate stigma, resilience and quality of life (QoL) among parents of children with ASD. Methods: Cross-sectional study of 144 parents of children with ASD were recruited from two main tertiary hospitals in Kelantan, Malaysia, a developing country in Southeast Asia. Pearson correlation was used to examine the relationship between parental affiliate stigma, resilience and QoL. Simple and multiple linear regression analyses were used to identify the significant associated factors of affiliate stigma, resilience and QoL. Results: Correlational analyses revealed that perceived affiliate stigma demonstrated an inverse relationship with resilience and QoL. Additionally, resilience had a positive relationship with QoL. Regression analyses revealed that the father's employment status, the mother's level of education, having a disability card, the child's age at ASD diagnosis, comorbidities of the child and ASD severity perceived by parents were associated with parental affiliate stigma, resilience and QoL. Conclusion: Study findings highlight the contribution of socio-demographic characteristics of children with ASD and their families in the determination of affiliate stigma, resilience and QoL.

15.
Stroke ; 55(8): 2151-2162, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38946544

RESUMO

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.


Assuntos
AVC Isquêmico , Camundongos Knockout , Neurônios , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/agonistas , Camundongos , AVC Isquêmico/metabolismo , Masculino , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Reabilitação do Acidente Vascular Cerebral , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL
16.
Front Pharmacol ; 15: 1416010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035987

RESUMO

Background: With the remarkable effect of controlling the increase in drug costs by the first batch of National Key Monitoring and Rational Use Drugs (first NKMRUDs), the National Health Commission of the People's Republic of China releases the second NKMRUDs to further strengthen the reasonable use of drugs. Unfortunately, the second NKMRUDs include some drugs of National Volume-based Procurement and National Essential Medicines, which challenges the management of pharmaceutical affairs on the three kinds of drugs. Objective: The main objective of this study was to investigate the prevalence of the second NKMRUDs and explore their monitoring indicators. Methods: An adapted WHO methodology for point prevalence surveys was conducted for the second NKMRUDs. For the monitoring indicators, we sought to explore whether the defined daily dose (DDD) and days of therapy (DOT) can be suitable for the second NKMRUDs through comparing differences between DDD and DOT with the prescribed daily dose (PDD). Results: Among the 935 included patients, 29.20% of the patients received at least one of the second NKMRUDs. A total of 273 patients were administered with 487 times of the second NKMRUDs. Among them, 162 , 62 , and 49 patients were receiving one, two, and three or more agents, respectively. The most commonly prescribed second NKMRUDs were compound amino acids, budesonide, and ceftazidime. The total DDDs and DOTs of the second NKMRUDs were 3360.68 and 1819.80, respectively, with the PDDs of 1865.26. The deviations (80.17%) of DDDs from PDDs were significantly greater than those (-2.44%) of DOTs. Conclusion: The prevalence of the second NKMRUDs was obtained by using the adapted PPS methodology at a tertiary university hospital. The DOT indicator is found to more accurately reflect actual consumption than the DDD indicator for second NKMRUDs. It is recommended to use the DOT indicator to monitor second NKMRUDs.

17.
J Family Med Prim Care ; 13(6): 2477-2484, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39027832

RESUMO

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze-thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

18.
Toxins (Basel) ; 16(7)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39057952

RESUMO

Abrin and ricin, both type II ribosome-inactivating proteins, are toxins of significant concern and are under international restriction by the Chemical Weapons Convention and the Biological and Toxin Weapons Convention. The development of a rapid and sensitive detection method for these toxins is of the utmost importance for the first emergency response. Emerging rapid detection techniques, such as surface-enhanced Raman spectroscopy (SERS) and lateral flow assay (LFA), have garnered attention due to their high sensitivity, good selectivity, ease of operation, low cost, and disposability. In this work, we generated stable and high-affinity nanotags, via an efficient freezing method, to serve as the capture module for SERS-LFA. We then constructed a sandwich-style lateral flow test strip using a pair of glycoproteins, asialofetuin and concanavalin A, as the core affinity recognition molecules, capable of trace measurement for both abrin and ricin. The limit of detection for abrin and ricin was 0.1 and 0.3 ng/mL, respectively. This method was applied to analyze eight spiked white powder samples, one juice sample, and three actual botanic samples, aligning well with cytotoxicity assay outcomes. It demonstrated good inter-batch and intra-batch reproducibility among the test strips, and the detection could be completed within 15 min, indicating the suitability of this SERS-LFA method for the on-site rapid detection of abrin and ricin toxins.


Assuntos
Abrina , Ricina , Análise Espectral Raman , Ricina/análise , Abrina/análise , Análise Espectral Raman/métodos , Glicoproteínas/análise , Limite de Detecção , Humanos , Substâncias para a Guerra Química/análise , Substâncias para a Guerra Química/toxicidade
19.
Life Sci ; 352: 122869, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950644

RESUMO

AIMS: To detect the therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells (EPI-NCSCs) on repairing facial nerve defects by second near-infrared (NIR-II) fluorescence imaging. MATERIALS AND METHODS: Firstly, CelTrac1000-labeled EPI-NCSCs were microinjected into the acellular nerve allografts (ANAs) to bridge a 10-mm-long gap in the buccal branch of facial nerve in adult rats. Then, Celtrac1000-labeled EPI-NCSCs were detected by NIR-II fluorescence imaging system to visualize the behavior of the transplanted cells in vivo. Additionally, the effect of the transplanted EPI-NCSCs on repairing facial nerve defect was examined. KEY FINDINGS: Through 14 weeks of dynamic observation, the transplanted EPI-NCSCs survived in the ANAs in vivo after surgery. Meanwhile, the region of the NIR-II fluorescence signals was gradually limited to be consistent with the direction of the regenerative nerve segment. Furthermore, the results of functional and morphological analysis showed that the transplanted EPI-NCSCs could promote the recovery of facial paralysis and neural regeneration after injury. SIGNIFICANCE: Our research provides a novel way to track the transplanted cells in preclinical studies of cell therapy for facial paralysis, and demonstrates the therapeutic potential of EPI-NCSCs combined with ANAs in bridging rat facial nerve defects.


Assuntos
Traumatismos do Nervo Facial , Folículo Piloso , Regeneração Nervosa , Crista Neural , Células-Tronco Neurais , Imagem Óptica , Animais , Ratos , Crista Neural/citologia , Crista Neural/transplante , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Facial/terapia , Células-Tronco Neurais/transplante , Imagem Óptica/métodos , Ratos Sprague-Dawley , Masculino , Nervo Facial , Transplante de Células-Tronco/métodos , Quitosana/química
20.
Front Oncol ; 14: 1413273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962272

RESUMO

Background: Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis. Methods: CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay. Results: Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls. Conclusion: This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.

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