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Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.
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Peptídeos e Proteínas de Sinalização Intercelular , Paclitaxel , Doenças do Sistema Nervoso Periférico , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Humanos , Animais , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Feminino , Camundongos , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
BACKGROUND: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections. METHODS: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves. RESULTS: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers. CONCLUSIONS: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases.
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Infecções Assintomáticas , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/sangue , COVID-19/virologia , Masculino , Feminino , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Índice de Gravidade de Doença , Neutrófilos/imunologia , Proteína C-Reativa/análise , Biomarcadores/sangue , Basófilos , Curva ROC , AdolescenteRESUMO
PURPOSE: To comprehensively analyze the factors associated with different intensities of physical activity and sedentary behavior in newly diagnosed lung cancer patients in the early postoperative period, providing a basis for clinically tailored personalized intervention measures. METHODS: A cross-sectional study design was employed, and 915 patients newly diagnosed with lung cancer completed a questionnaire survey on demographics, disease, health-related fitness, and psychosocial factors. Physical activity levels and sedentary behaviors were assessed using the International Physical Activity Questionnaire. Data were analyzed using SPSS 25.0. RESULTS: The physical activity level of walking amounted to 1265.4 ± 1025.8 MET-min/week, potentially influenced by factors such as region, depression, health behavior capacity, and lactate dehydrogenase. The moderate-intensity physical activity level stood at 529.8 ± 976.5 MET-min/week, subject to influences like regional lymph node staging, body mass index, and albumin levels, among other factors. The high-intensity physical activity level was 111.1 ± 731.0 MET-min/week, potentially affected by region, grip strength, health behavior capacity, and other factors. Sedentary time averaged 5 ± 3 h/day, potentially influenced by work conditions, red blood cell values, and other factors. CONCLUSION: In patients newly diagnosed with lung cancer, early postoperative walking activities predominate, with less engagement in high-intensity physical activity and prolonged sedentary time. Physical activity and sedentary behavior may be influenced by various factors such as geography, physiology, psychology, and health-related fitness. To enhance the quality of life of patients with lung cancer in the early postoperative period, tailored intervention measures should be devised based on the circumstances of the individual patients.
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Neoplasias Pulmonares , Comportamento Sedentário , Humanos , Estudos Transversais , Masculino , Feminino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/psicologia , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Período Pós-Operatório , Adulto , Exercício Físico/fisiologia , Comportamentos Relacionados com a Saúde , Caminhada/fisiologiaRESUMO
Drug-related problems (DRPs) are critical medical issues during transition from hospital to home with high prevalence. The application of a variety of interventional strategies as part of the transitional care has been studied for preventing DRPs. However, it remains challenging for minimizing DRPs in patients, especially in older adults and those with high risk of medication discrepancies after hospital discharge. In this narrative review, we demonstrated that age, specific medications and polypharmacy, as well as some patient-related and system-related factors all contribute to a higher prevalence of transitional DPRs, most of which could be largely prevented by enhancing nurse-led multidisciplinary medication reconciliation. Nurses' contributions during transitional period for preventing DRPs include information collection and evaluation, communication and education, enhancement of medication adherence, as well as coordination among healthcare professionals. We concluded that nurse-led strategies for medication management can be implemented to prevent or solve DRPs during the high-risk transitional period, and subsequently improve patients' satisfaction and health-related outcomes, prevent the unnecessary loss and waste of medical expenditure and resources, and increase the efficiency of the multidisciplinary teamwork during transitional care.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Reconciliação de Medicamentos , Cuidado Transicional , Humanos , Reconciliação de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Polimedicação , Adesão à Medicação , Idoso , Alta do Paciente , Conduta do Tratamento MedicamentosoRESUMO
Objective: Due to the escalating global prevalence of allergic rhinitis (AR) and its status as an independent risk factor for asthma, timely and effective control of AR is crucial. Achieving this often involves the accurate assessment of AR. Currently, the Control of Allergic Rhinitis and Asthma Test (CARAT) is widely used as an assessment tool, but its measurement effectiveness in Chinese AR patients remains unclear. Therefore, this study aims to evaluate the reliability and validity of the Chinese version of the CARAT10 scale (CARAT10-C) and analyze its application value in the assessment of allergic rhinitis and asthma control trials. Methods: The study enrolled 130 patients with AR from the Ear, Nose, and Throat (ENT) outpatient department of a comprehensive teaching hospital from March to May 2022 as participants. The reliability and validity of the CARAT10-C scale were assessed using Cronbach's alpha coefficient (CAC), Kaiser-Meyer-Olkin (KMO), and Bartlett's sphericity test. Additionally, the study analyzed the effectiveness of the CARAT10-C scale in its application within the Control of Allergic Rhinitis and Asthma Test (CARAT). Results: The Cronbach's alpha coefficient ranges between 0 and 1, with higher values indicating better reliability. Significant differences in exploratory factor analysis suggest good validity. The Cronbach's alpha coefficient of the CARAT10-C scale was 0.806. Exploratory factor analysis revealed that the eigenvalues of Component 1 (3.851) and Component 2 (2.193) were both greater than 1, with a cumulative variance contribution rate (CVCR) of 60.436%. Items 6-10 were primarily loaded on Component 1 (Asthma), while items 1-4 were mainly influenced by Component 2 (AR), with loading ranges of 0.508-0.874, all significant at P < .001. The composite reliability (CAC) of the CARAT10-C scale was 0.806, exceeding 0.8, indicating high reliability. Component 1 had a CAC of 0.834, and Component 2 had a CACs of 0.807, both exceeding 0.8, indicating high reliability for both components. Conclusion: The CARAT10-C scale demonstrates good reliability and validity in the preliminary assessment of AR. It holds potential value in the evaluation and management of AR in China, although the specific application effects still require further investigation.
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Asma , Rinite Alérgica , Humanos , Rinite Alérgica/diagnóstico , Masculino , Feminino , Adulto , Reprodutibilidade dos Testes , Asma/diagnóstico , Pessoa de Meia-Idade , China , Adulto Jovem , Inquéritos e Questionários/normas , Traduções , AdolescenteRESUMO
Objective: To observe the effect of implementing standardized flow management in enteral nutrition therapy for critically ill patients. Methods: We selected 241 critically ill patients admitted to our hospital from January 2020 to January 2023. Patients with enteral nutrition without standard process management were set as the control group (n = 109), while those with enteral nutrition and standard process management were set as the observation group (n = 132). The total protein, albumin, prealbumin, and hemoglobin were compared between the two groups on the 7th and 14th day of nutritional therapy. Immune indicators (IgM, IgA, and IgG), NUTRIC score, and the incidence of infectious complications were compared between the two groups. Results: On the 7th and 14th day of treatment, the total protein, albumin, prealbumin, hemoglobin, and immune indicators in the observation group were higher than those in the control group, and the differences were statistically significant (P < .05). On the 7th and 14th day of treatment, the NUTRIC score of the observation group was higher than that in the control group, with a statistically significant difference (P < .05). The incidence of infectious complications in the observation group was lower than that in the control group, and the difference was statistically significant (P < .05). Conclusion: Implementing standardized process management of EN for critically ill patients improves total protein, albumin, prealbumin, hemoglobin, immune indexes, NUTRIC score, and nutritional status, while reducing the incidence of infectious complications. These findings offer valuable insights for clinical practice and advocate for practical application.
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BACKGROUND: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. METHODS: Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. RESULTS: NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. CONCLUSION: These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.
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NUAK1 is a serine/threonine kinase that has been shown to be associated with poor prognosis in several cancers. Although NUAK1 is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC), the actual role of NUAK1 and the mechanism of its overexpression in HCC has yet to be reported. In the present study, we found that NUAK1 expression was significantly increased in human HCC tumor tissues. Overexpression of NUAK1 dramatically enhanced HCC cells proliferation and migration in vitro. Stable induction of NUAK1 expression promoted tumor growth and tumor metastases to the lungs in the subcutaneous xenograft models and intravenous metastasis models. At the cellular level, enforced expression of Dickkopf-1 (DKK1) activated the Akt signaling pathway, thereby promoting the mRNA and protein expression of NUAK1 in HCC cells. By contrast, depletion of DKK1 was found to attenuate the mRNA and protein expression of NUAK1. In the subcutaneous xenograft models, stable induction of DKK1 expression not only accelerated tumor growth but also increased p-Akt and NUAK1 expression; whereas knockdown of DKK1 inhibited tumor growth, p-Akt and NUAK1 expression. Furthermore, immunohistochemical analysis of 20 HCC clinical samples showed that the expression level of NUAK1 was positively correlated with DKK1 and p-Akt. Taken together, we provide the first evidence that DKK1 promotes NUAK1 transcriptional expression via the activation Akt in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , RNA Mensageiro , Modelos Animais de Doenças , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas Quinases/metabolismo , Proteínas Repressoras/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismoRESUMO
INTRODUCTION: The efficacy and safety of autologous fat grafting for use in oncology patients are controversial. Patients with head and neck cancer have complex anatomy and require reconstructive repair of the head and neck after comprehensive treatment. The limited additional aesthetic and functional studies on the use of autologous fat fillers in patients with head and neck cancer are unclear. This study systematically evaluates the additional function of autologous fat fillers in the head and neck and systematically reviews issues related to autologous fat grafting after comprehensive head and neck cancer treatment, including current indications, techniques, potential complications, graft survival, and patient satisfaction. METHODS: A systematic literature review was performed using PubMed, The Cochrane Library, EMBASE, and Web of Science (last accessed on January 9, 2023). RESULTS: A total of 249 cases of autologous fat fillers in patients with head and neck cancer were reported in 10 clinical publications. Observations were based mainly on subjective physician and patient evaluation indicators, and all studies reported the beneficial effects of autologous fat fillers on aesthetics and function after treatment for head and neck cancer. CONCLUSIONS: Autologous fat fillers are effective in improving the aesthetics and function of head and neck cancer, and due to the limitations of the original study, future studies with large samples are needed to support this. PROSPERO registration number is CRD42020222870. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Tecido Adiposo , Neoplasias de Cabeça e Pescoço , Humanos , Resultado do Tratamento , Tecido Adiposo/transplante , Transplante Autólogo/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Estética , Estudos RetrospectivosRESUMO
We aimed to review and synthesise the evidence of the interventions of patients' and informal caregivers' engagement in managing chronic wounds at home. The research team used a systematic review methodology based on an updated guideline for reporting systematic reviews (PRISMA) and recommendations from the Synthesis Without Meta-analysis. Cochrane Central Register of Controlled Trial of the Cochrane Library, Pubmed, Embase, CINAHL, Wanfang (Chinese), and CNKI database (Chinese) were searched from inception to May 2022. The following MESH terms were used: wound healing, pressure ulcer, leg ulcer, diabetic foot, skin ulcer, surgical wound, educational, patient education, counselling, self-care, self-management, social support, and family caregiver. Experimental studies involving participants with chronic wounds (not at risk of wounds) and their informal caregivers were screened. Data were extracted and the narrative was synthesised from the findings of included studies. By screening the above databases, 790 studies were retrieved, and 16 met the inclusion and exclusion criteria. Studies were 6 RCTs and ten non-RCTs. Outcomes of chronic wound management included patient indicators, wound indicators, and family/caregiver indicators. Home-based interventions of patients or informal caregivers' engagement in managing chronic wounds at home may effectively improve patient outcomes and change wound care behaviour. What's more, educational/behavioural interventions were the primary type of intervention. Multiform integration of education and skills training on wound care and aetiology-based treatment was delivered to patients and caregivers. Besides, there are no studies entirely targeting elderly patients. Home-based chronic wound care training was important to patients with chronic wounds and their family caregivers, which may advance wound management outcomes. However, the findings of this systematic review were based on relatively small studies. We need more exploration of self and family-oriented interventions in the future, especially for older people affected by chronic wounds.
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Úlcera por Pressão , Úlcera Cutânea , Humanos , Idoso , Cuidadores , Apoio Social , Autocuidado , Úlcera por Pressão/prevenção & controleRESUMO
OBJECTIVE: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. METHODS: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. RESULTS: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. CONCLUSION: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.
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Meridianos , Tramadol , Humanos , Masculino , Medicina Tradicional Chinesa , Flatulência , Dor Pós-Operatória/tratamento farmacológico , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/uso terapêutico , Tramadol/uso terapêutico , Fentanila/uso terapêuticoRESUMO
Precisely modulated photoluminescence (PL) with external control is highly demanded in material and biological sciences. However, it is challenging to switch the PL on and off in the NIR region with a high modulation contrast. Here, we demonstrate that reversible on and off switching of the PL in the NIR region can be achieved in a bicomponent system comprised of PbS semiconducting nanocrystals (NCs) and diarylethene (DAE) photoswitches. Photoisomerization of DAE to the ring-closed form upon UV light irradiation causes substantial quenching of the NIR PL of PbS NCs due to efficient triplet energy transfer. The NIR PL fully recovers to an on state upon reversing the photoisomerization of DAE to the ring-open form with green light irradiation. Importantly, fully reversible switching occurs without obvious fatigue, and the high PL on/off ratio (>100) outperforms all previously reported assemblies of NCs and photoswitches.
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Luminescência , Nanopartículas , Nanopartículas/químicaRESUMO
Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.
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Nefrite Intersticial , Selenometionina , Animais , Antioxidantes , Flavonoides , Camundongos , NF-kappa B/metabolismo , Nefrite Intersticial/tratamento farmacológico , Selenometionina/farmacologia , Selenometionina/uso terapêutico , Receptor 4 Toll-Like/genéticaRESUMO
Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1-induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO-1, Occludin, and Claudin-1), decreased intestinal permeability, reduced production of gut-derived Lipopolysaccharide (LPS) and remodeled gut microbiota, ultimately alleviated AFB1-induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic-treated mice. Meanwhile, MT pretreatment significantly increased the farnesoid X receptor (FXR) protein expression of ileum, and decreased the TLR4/NF-κB signaling pathway-related messenger RNA (mRNA) and proteins (TLR4, MyD88, p-p65, and p-IκBα) expression in livers of AFB1-exposed mice. Subsequently, pretreatment by Gly-ß-MCA, an intestine-selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver-specific expression of TLR4/NF-κB signaling pathway-related mRNA and proteins (TLR4, MyD88, p-p65, and p-IκBα). In conclusion, MT pretreatment ameliorated AFB1-induced liver injury and the potential mechanism may be related to regulate gut microbiota/intestinal FXR/liver TLR4 signaling axis, which provides a strong evidence for the protection of gut-derived liver inflammation.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Melatonina , Aflatoxina B1/toxicidade , Animais , Humanos , Inflamação , Fígado/metabolismo , Melatonina/farmacologia , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Ochratoxin A (OTA) is universally known to induce nephrotoxicity via inducing oxidative stress and apoptosis, inhibiting protein synthesis and activating autophagy. Our previous studies have proved that OTA induces nephrotoxicity in vitro and in vivo by adjusting the NOD-like receptor protein 3 (NLRP3) inflammasome activation and caspase-1-dependent pyroptosis. Based on these findings, we further investigated the protective role of selenomethionine (SeMet) on OTA-caused nephrotoxicity using the Madin-Darby canine kidney (MDCK) epithelial cells as an in vitro model, proposing to offer a new way for remedying OTA-induced nephrotoxicity by nutritional manipulation. We measured the cell vitality, lactate dehydrogenase (LDH) activity and the expression of renal fibrotic genes, NLRP3 inflammasome and pyroptosis related genes. MTT and LDH results indicated that SeMet supplementation significantly mitigated 2.0 µg/ml OTA-induced cytotoxicity in MDCK cells (p < 0.05). Meanwhile, SeMet alleviated OTA induced increase of reactive oxygen species in MDCK cells. Then, the expressions of α-SMA, Vimentin, and TGF-ß were detected both in mRNA and protein levels. The results indicated 8 µM SeMet supplementation could significantly downregulate the expression of OTA-induced renal fibrosis-related genes (p < 0.05). In addition, the upregulation of OTA-induced NLRP3 inflammasome and pyroptosis downstream genes was also significantly inhibited by 8 µM of SeMet (p < 0.05). In summary, SeMet could alleviate OTA-induced renal fibrotic genes expression and reduce NLRP3-caspase-1-dependent pyroptosis. Therefore, SeMet supplementation may become an effective approach for preserving animals from renal injury exposed to OTA.
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Regulação da Expressão Gênica/efeitos dos fármacos , Nefropatias/metabolismo , Ocratoxinas/toxicidade , Piroptose/efeitos dos fármacos , Selenometionina/farmacologia , Animais , Cães , Fibrose , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Células Madin Darby de Rim CaninoRESUMO
Ochratoxin A (OTA), frequently existing in the food and feeds, could induce immunotoxicity. Porcine circovirus type 2 (PCV2), as a primary causative agent of porcine circovirus-associated disease, also could induce immunosuppression. However, it is still unknown whether PCV2 infection impacts OTA-induced immunotoxicity. The pigs and porcine alveolar macrophages (PAMs) were used as the model in the present experiment. The results in vivo indicated that PCV2 infection exacerbated OTA-induced immunotoxicity, NF-κB p65 phosphorylation, and TLR4 and MyD88 mRNA and protein expression in spleen. The results in vitro showed that OTA at 7.0 and 9.0 µM decreased cell viability and increased LDH release of PAMs without PCV2 infection. However, with PCV2 infection, OTA at 5.0, 7.0 and 9.0 µM significantly decreased cell viability and increased LDH release compared with absence of PCV2 infection. In addition, OTA at 5.0 and 7.0 µM significantly increased Annexin V/PI-positive rate, apoptosis of nuclear, γ-H2AX foci, IL-1α and TNF-α expression in PAMs with PCV2 infection compared with absence of PCV2 infection. In addition, PCV2 infection enhanced OTA-induced TLR4 and MyD88 mRNA and protein expression and NF-κB p65 phosphorylation. Knockdown of TLR4 alleviated the exacerbating effects of PCV2 infection on OTA-induced cytotoxicity, apoptosis and DNA damage in PAMs. These results indicated that PCV2 infection aggravated OTA-induced immunotoxicity and reduced the dose of OTA-induced immunotoxicity via TLR4/NF-κB p65 signaling pathway, which could provide basis for establishing limits for OTA.
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Circovirus , Ocratoxinas , Animais , Macrófagos Alveolares , Ocratoxinas/toxicidade , Transdução de Sinais , SuínosRESUMO
BACKGROUND: The 2019 coronavirus disease (COVID-19) is a global public health emergency. So far, only a limited number of studies have investigated the impact of the COVID-19 pneumonia pandemic on the mental health of parents having children with cancer. This study investigated the hope, and relevant influencing factors (depression, anxiety, demographic data) among parents whose children had retinoblastoma (RB) during the COVID-19 pandemic. METHODS: A cross-sectional survey and a convenient sampling survey were conducted on 317 parents of RB children admitted to the Ninth People's Hospital affiliated with Shanghai Jiao Tong University, School of Medicine, and Qilu Children's Hospital of Shandong University. The survey tools included Demographic Questionnaire, Herth Hope Index (HHI), The Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaires (PHQ)-2. RESULTS: The hope level score of the parents of RB patients was (35.36 ± 4.42), which was at the medium level. The highest dimension of hope score was inner positive readiness and expectancy (12.07 ± 1.57), and the lowest dimension was interconnectedness with self and others (11.50 ± 1.64). The incidence rate of depression and anxiety was 29.97% (95/317) and 41.32% (131/317), respectively. Monoculus or binoculus disease, sleep status, health status, and depression /anxiety had statistically significant effects on the parental hope level (p < 0.05). Multiple linear regression analysis revealed that time since diagnosis, education level, treatment type and depression were independent influencing factors (p < 0.05), accounting for 22.60% of the variation in hope level. CONCLUSION: During the COVID-19 pandemic, medical staff should formulate targeted intervention measures according to different characteristics of ocular disease, time since diagnosis, treatment type, parental educational level and emotional state in order to improve the level of parental hope.
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COVID-19 , Neoplasias da Retina , Retinoblastoma , Ansiedade/epidemiologia , Criança , China , Estudos Transversais , Depressão/epidemiologia , Humanos , Pandemias , Pais , Retinoblastoma/epidemiologia , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
BACKGROUND: As China is still in the process of establishing the hierarchical medical system, people have full autonomy in choosing medical institutions when they need to see a doctor. The basic working of a hierarchical medical system involves four parts: primary treatment at the community level, two-way referral, a partition of emergency and chronic disease, and a joint effort among different healthcare facilities. This study examines factors associated with primary healthcare use in a middle-aged and elderly Chinese population. METHODS: Our study is a cross-sectional and observational survey involving 1659 adults aged 45 and above. The data are from the 2015 China Health and Retirement Longitudinal Study. According to the Andersen behavioral model, we used logistic regression to analyze the influencing factors of healthcare services utilization, including predisposing, enabling, and need factors. We also compared the relative importance of factors to healthcare services utilization by analysis of variance. RESULTS: During the recently 1-month period, 63.89% of the sample had their last visit to a primary healthcare facility. In the final logistic model, there were three predisposing characteristics (education level, children number, and work status), three enabling factors (household status, out-of-pocket expenses, and travel time to the healthcare facilities), and one need factor (three specific chronic diseases) were significantly associated with primary healthcare use. Having received more education, taking more travel time to the healthcare facility, paying more out-of-pocket expenses, and having heart problems were associated with a lower probability of choosing the primary healthcare facility. However, having more children, being still at work, with agricultural household status, diabetes, and arthritis were associated with a higher likelihood of having primary healthcare facility visits. Among all the factors, the three most powerful determinants were out-of-pocket expenses, travel time to the healthcare facility, and education. CONCLUSIONS: Policymakers need to consider these factors when improving the system of primary treatment at the community level, including improving reimbursement policy to distinguish the payment standard between hospitals and primary healthcare facilities.
Assuntos
Gastos em Saúde , Adulto , Idoso , Criança , China , Doença Crônica , Estudos Transversais , Humanos , Estudos Longitudinais , Pessoa de Meia-IdadeRESUMO
The objectives of this study were to investigate the status and influence factors of caregiver's quality of life (QOL) on caring for patients with chronic wound during COVID-19 epidemic. A prospective cross-sectional study of 83 informal caregivers was included. The characteristics of informal caregivers as well as their QOL assessment by the Family Dermatology Life Quality Index (FDLQI) were measured, respectively. Single-factor analysis and multiple regression analysis were carried out to explore the independent influence factors of QOL of caregiver on caring for patient with chronic wound. 62.65% of the caregivers were female with a mean age of (54.24 ± 12.6) years, and 34.9% of the caregivers were parents. The mean FDLQI score was 13.01 ± 7.53 at a high level. The following variables influenced the FDLQI scores of caregivers: self-care ability of patients, patient's satisfaction of home-based wound care, and home-based wound care need of caregivers. The model was able to explain 29.9% of variance in QOL of caregiver (F = 6.561, P = .000, R2 = 0.299, adjusted R2 = 0.253). In conclusion, the impact of chronic wound disease on the QOL of caregivers is heavy during COVID-19 epidemic. Wound professionals are suggested to pay attention to wound care need at home and QOL of caregiver on caring for patients with chronic wound during COVID-19 epidemic and develop tailored wound health education and support programme in order to improve the QOL of caregivers.
Assuntos
COVID-19 , Cuidadores , Qualidade de Vida , Ferimentos e Lesões/terapia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Assistência ao Paciente , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
AIM: To comprehensively introduce the prevention and control measures that we can take in dental clinics during the pandemic period of coronavirus disease 2019 (COVID-19) and provide some practical experience for the development of nursing and health policies applicable to COVID-19. BACKGROUND: The outbreak of COVID-19 has placed the global health system under threat, which seriously influences the normal operations of human society. Safe and effective nursing measures should be taken to ensure the normal operation of dental clinics. SOURCES OF EVIDENCE: We searched and referenced many references on the PubMed database. Through the combination of related literatures and our experience, we describe various strategies, including personnel management, personal protection, disinfection and isolation, adopted in the dental clinic of our Chinese hospital during the pandemic of COVID-19. DISCUSSION/CONCLUSIONS: We introduced strategies for the nursing staff in dental clinics to assist them with the prevention and control of COVID-19. The successful implementation of the protective measures could ensure the safety of medical staff and patients, and contributed to the normal operation of dental clinics during the pandemic period. CONCLUSIONS FOR NURSING AND HEALTH POLICY: During the pandemic, frontline nurses are under physical and mental pressure facing the threat of infection while at work. In addition to pandemic prevention, we should also pay attention to the needs of nursing staff. More reasonable and effective nursing and health policies should be formulated to ensure their safety and protect their rights and interests. This is the only way that the prevention and control of COVID-19 can be achieved, and we can prepare for future public health events.