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Caffeic acid (CA) is a natural polyphenol that can have various positive effects on human health. However, its extraction and processing can cause significant ecological issues. Therefore, it is crucial to detect and degrade CA effectively in the environment. In this study, we have developed a multifunctional magnetic luminescent nanozyme, Fe3O4@CeO2/Tb-MOF, which combines peroxidase activity to detect and degrade CA. The fluorescence of the nanozyme was significantly attenuated due to the specific nucleophilic reaction between its boronic acid moiety and the o-diphenol hydroxyl group of CA, energy competition absorption and photo-induced electron transfer (PET) effect. This nanozyme demonstrates a linear detection range from 50 nM to 500 µM and an exceptionally low detection limit of 18.9 nM, along with remarkable selectivity and stability. Moreover, the synergistic catalysis of Fe3O4 and CeO2 within Fe3O4@CeO2/Tb-MOF fosters peroxidase activity, leading to the generation of substantial free radicals catalyzed by H2O2, which ensures the efficient degradation of CA (â¼95%). The superparamagnetic property of Fe3O4 further enables the efficient reuse and recycling of the nanozyme. This research provides a novel approach for the concurrent detection and remediation of environmental contaminants.
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Fluorescence imaging technology is a versatile and essential tool in the field of biomedical research. To obtain excellent imaging results, the precise labeling of fluorescent probes is an important prerequisite. Nevertheless, the labeling selectivity of most fluorescent probes is not satisfactory, new design concepts are desperately needed. In this context, two isomeric lipid droplets (LDs) fluorescent probes Lipi-Cz-1 and Lipi-Cz-2 have been sophisticatedly developed with TICT and ICT-emitting characteristic, respectively. The more environmentally sensitive TICT-emitting Lipi-Cz-1 exhibits a significantly enhanced labeling selectivity in LDs imaging compared to the ICT-emitting Lipi-Cz-2, sufficiently illustrating the effectiveness of TICT-emitting characteristic in improving labeling selectivity. Additionally, Lipi-Cz-1 displays high photostability and biocompatibility. These advantages enable Lipi-Cz-1 to be finely applied in multimode fluorescence imaging, e.g. time-lapse 3D confocal imaging to monitor changes of the number and size of LDs during starvation, two-photon 3D imaging to compare the variations of LDs in various liver tissues, and STED super-resolution imaging to visualize the nanoscale LDs with the resolution of 65 nm. Overall, these imaging findings validate the effectiveness of the new strategy for improving the labeling selectivity.
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Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.
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Citocinas , Modelos Animales de Enfermedad , Huésped Inmunocomprometido , Replicación Viral , Infección por el Virus Zika , Virus Zika , Animales , Virus Zika/inmunología , Virus Zika/patogenicidad , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virología , Replicación Viral/efectos de los fármacos , Ratones , Citocinas/metabolismo , Tasa de Supervivencia , Receptor de Interferón alfa y beta/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Receptores de Interferón/deficiencia , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Receptor de Interferón gamma , Células VeroRESUMEN
Accurate on-site detection of nitrite in complex matrices remains a significant challenge. Herin, we construct a self-ratio optical bimodal portable kit via co-assembling NaErF4:0.5%Tm@NaYF4@NaYbF4:0.5%Tm@NaYF4 (Er:Tm@Yb:Tm) and nitrogen-doped carbon platinum nanomaterials (Pt/CN) in sodium alginate (SA) hydrogel. Pt/CN nanomaterials are synthesized by high-temperature sintering using a zinc-based zeolite imidazolium framework as a sacrificial template. The Pt/CN nanozyme possesses excellent oxidase-like activity to produce the oxidation state 3,3',5,5'-tetramethylbenzidine (oxTMB). Nitrite mediates diazotization of oxTMB to trigger the change of absorption signals, accompanying the ratio fluorescence response of the Er:Tm@Yb:Tm. Crucially, Er:Tm@Yb:Tm and Pt/CN are embedded in SA hydrogel to fabricate a portable kit with efficient and sensitive performance. An image processing algorithm is used to analyze the nitrite-induced signal change of the portable hydrogel kit, resulting in detection limits of 0.63 µM. This method has great potential for point-of-care applications due to its reliability, long-term stability, accuracy, sensitivity, and portability.
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Técnicas Biosensibles , Hidrogeles , Límite de Detección , Nitritos , Teléfono Inteligente , Técnicas Biosensibles/métodos , Nitritos/análisis , Hidrogeles/química , Humanos , Bencidinas/química , Nanoestructuras/química , Platino (Metal)/químicaRESUMEN
Reversed-phase liquid chromatography (RPLC) represents an effective separation method, and is widely employed as the second dimension in most 2D-LC systems. Nevertheless, the solvent effect of the eluent from the first dimension on RPLC presents a challenge to the online coupling of RPLC with other separation modes, particularly normal phase liquid chromatography (NPLC). To address this issue, a comprehensive understanding of the solvent effect is essential. Following a comprehensive investigation into the influence of diverse solvents on RPLC separations, it was observed that alkane solvents, such as n-hexane, exhibited a pronounced tendency to be retained during RPLC separations. Such solvents do not affect the analysis of samples with weaker retention abilities than themselves, even when a large injection volume is used. The solvent effect was thus reduced by employing n-hexane-based solvent dilution. Leveraging the markedly enhanced solvent tolerance and extensive injection volume in RPLC, a versatile integration of the NPLC and RPLC was devised, necessitating merely a purge pump and a 10 port 2 position valve in conjunction with two sample loops. The novel 2D-LC system was then deployed for the analysis of propolis, a naturally occurring complex sample, and demonstrated remarkable separation efficiency.
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Quaternary ammonium salt bactericides are broad-spectrum bactericides often used in oral care products because of their high antibacterial efficacy, strong penetration, and low toxicity. However, the excessive use of quaternary ammonium salt bactericides may cause contact dermatitis, scalding poisoning, and even death. Existing methods to determine quaternary ammonium salt bactericides are unable to meet current requirements owing to the lack of determination components. Therefore, establishing a simple and accurate method for the simultaneous detection of more quaternary ammonium salt bactericides is necessary. In this study, a method that couples sample pretreatment with high performance liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) was developed for the simultaneous determination of quaternary ammonium salt bactericides in oral care products, including dodecyltrimethylammonium chloride, dodecyldimethylbenzylammonium chloride, benzethonium chloride, tetradecyl trimethyl ammonium chloride, tetradecyldimethylbenzylammonium chloride, N-hexadecyltrimethylammonium chloride, benzyldimethylhexadecylammonium chloride, trimethylstearylammonium chloride, stearyldimethylbenzylammonium chloride, and docosyltrimethylammonium chloride. Some of these bactericides do not absorb ultraviolet light, so a universal evaporative light-scattering detector was used owing to testing cost and stability concerns. The paste samples contained thickening agents, which are highly soluble in water but insoluble in organic solvents; these agents can seriously affect the results of sample pretreatment and damage the chromatographic column. Hence, sample dehydration was necessary. In this study, four dehydration methods were compared. Anhydrous sodium sulfate (Na2SO4) was selected, and the amount of Na2SO4 was optimized. Based on the solubility of the 10 target compounds and extraction efficiency, three extraction solvents were compared, and ethanol was selected. Ultrasonic extraction was the primary extraction process used in this study. The effects of different ultrasonication times, temperatures, and powers on the extraction recoveries were also investigated. Ultimately, the optimized conditions were as follows: extraction of the dehydrated paste and powder samples using ethanol at room temperature (25 â) for 20 min under 100 W ultrasound power, and dilution of the liquid sample with ethanol. After extraction, the samples were separated on an Acclaim Surfactant column (150 mm×4.6 mm, 5 µm) with 50 mmol/L ammonium acetate aqueous solution (pH=5.5) (A) and acetonitrile (B) as mobile phases. The gradient elution program were as follows: 0-5.0 min, 75%A-35%A, 5.0-15.0 min, 35%A-20%A, 15.0-20.0 min, 20%A, 20.0-21.0 min, 20%A-75%A, 21.0-25.0 min, 75%A. An external standard method was used for quantitative determination. The 10 compounds were analyzed within 25 min. Linear equations, correlation coefficients, and linear ranges were obtained by analyzing a series of mixed standard working solutions. The limits of detection (LODs, S/N=3) and quantification (LOQs, S/N=10) of the 10 components were determined. Stearyldimethylbenzylammonium chloride and docosyltrimethylammonium chloride showed good linear relationships in the range of 10-200 mg/L, while the other compounds demonstrated good linear relationships in the range of 5-100 mg/L. In all cases, correlation coefficients (R2) of no less than 0.9992 were obtained. The LODs and LOQs were in the range of 1.42-3.31 mg/L and 4.25-9.94 mg/L, respectively. Ten analytes were spiked in blank matrices, such as toothpaste (paste), mouthwash (liquid), and dentifrice powder (powder) at three levels, and the recoveries and precisions were calculated. The average recoveries were 87.9%-103.1%, and the corresponding relative standard deviations (RSDs) did not exceed 5.5% (n=6). The developed method was used to detect 109 oral care products. Benzyldimethylhexadecylammonium chloride and stearyldimethylbenzylammonium chloride revealed high detection rates. Moreover, the amount of stearyldimethylbenzylammonium chloride in one toothpaste sample exceeded regulatory requirements. Given its advantages of good precision and accuracy, the developed method is suitable for the quantitative analysis of the 10 aforementioned compounds in typical oral care products. The study findings can serve as a reference for the quality and safety monitoring of oral care products.
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Compuestos de Amonio Cuaternario , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/análisis , Cromatografía Líquida de Alta Presión , Antibacterianos/análisis , Luz , Dispersión de RadiaciónRESUMEN
BACKGROUND: Solid pediatric tumors refer to cancers that affect children and adoles-cents, and they present unique challenges due to their distinct biological characteristics and their vulnerability to young patients. This study aims to shed light on addressing anemia and the causes of anemia in patients with solid pediatric tumors. MATERIALS AND METHODS: This retrospective cohort comprised 200 healthy children as controls and 235 patients with solid tumors. The study was conducted at first Affiliated Hospital of Zhengzhou University between January 2020 and June 2023. We evaluated different parameters of blood components in controls and patients with solid tumors such as medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and patients with only these tumors 3 weeks after the first cycle of chemotherapy. Further, we evaluated the relationship between serum ferritin and the weight of patients and assessed the relationship be-tween anemia and metastasis to the bone marrow in patients with neuroblastoma and hepatoblas-toma. RESULTS: We observed various combinations of derangements in blood parameters such as hemo-globin, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscu-lar hemoglobin concentration, hematocrit, red cell distribution width, white blood cells, and plate-let in medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and 3 weeks after first cycle of chemotherapy. We found a significant correlation between serum ferritin levels and weight in neuroblastoma patients who are ≤ 2 years (p = 0.022). Involvement of tumor cells in bone marrow correlates with decreased Hb levels in both neuroblastoma (CI = 93.21-106.68, p = 0.001) and hepatoblastoma (CI = 113.36-121.00, p = 0.001). CONCLUSION: Anemia may manifest as an early symptom in neuroblastoma, hepatoblastoma, and nephroblastoma. Also, anemia may be worse in patients with neuroblastoma and hepatoblastoma after chemotherapy and might warrant anemia therapy.
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BACKGROUND: There are relatively few studies on continuing care of coronary heart disease (CHD), and its research value needs to be further clarified. AIM: To investigate the effect of continuous nursing on treatment compliance and side effect management in patients with CHD. METHODS: This is a retrospective study with patients from January 2021 to 2023. The study was divided into two groups with 30 participants in each group. Self-rating anxiety scale (SAS) and Self-rating depression scale (SDS) were used to assess patients' anxiety and depression, and medical coping questionnaire was used to assess patients' coping styles. The pelvic floor dysfunction questionnaire (PFDI-20) was used to assess the status of pelvic floor function, including bladder symptoms, intestinal symptoms, and pelvic symptoms. RESULTS: SAS score decreased from 57.33 ± 3.01before treatment to 41.33 ± 3.42 after treatment, SDS score decreased from 50.40 ± 1.45 to 39.47 ± 1.57. The decrease of these two indexes was statistically significant (P < 0.05). PFDI-20 scores decreased from the mean 16.83 ± 1.72 before treatment to 10.47 ± 1.3the mean after treatment, which was statistically significant (P < 0.05). CONCLUSION: The results of this study indicate that pioneering research in continuous care of CHD has a positive impact on improving patients' treatment compliance, reducing anxiety and depression levels, and improving coping styles and pelvic floor functional status.
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PURPOSE: Identify users' needs for pediatric upper extremity (UE) exoskeletons and how users would like exoskeletons to serve their needs. METHODS: Qualitative study design with semi-structured interviews performed with families who are English-speaking with a child aged 3 to 16 years with a chronic need for UE assistance to perform activities. Content analysis was conducted for the responses. RESULTS: Twenty-two parents and 12 children among 21 families participated. Families identified key personal care, function and mobility, manual interaction, academic, recreational, and social activities they would like devices to support. Families rated the importance of a variety of design factors. Families using UE wearable assistive devices noted that they better met their functional needs relative to other needs. Families provided design suggestions for future exoskeletons, including preferences for attachment mechanisms, fasteners, and control systems. CONCLUSIONS: This study provides important information to guide the prescription and design of UE exoskeletons for pediatric populations.
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Niños con Discapacidad , Dispositivo Exoesqueleto , Investigación Cualitativa , Extremidad Superior , Humanos , Niño , Extremidad Superior/fisiopatología , Adolescente , Femenino , Masculino , Preescolar , Niños con Discapacidad/rehabilitación , Entrevistas como Asunto , Evaluación de Necesidades , Dispositivos de Autoayuda , Padres/psicologíaRESUMEN
Background: Functional dyspepsia is a highly prevalent digestive disorder. The limited effectiveness of current pharmaceutical interventions necessitates the exploration of alternative therapeutic options for functional dyspepsia. Xiangsha liujunzi decoction, a well-known traditional Chinese medicine formulation, has been widely employed in the treatment of functional dyspepsia in China. Nevertheless, the effectiveness of Xiangsha liujunzi decoction in the treatment of functional dyspepsia remains uncertain. Objective: To examine the effectiveness and safety of Xiangsha liujunzi decoction for treating functional dyspepsia. Methods: We retrieved seven databases containing randomized controlled trials on functional dyspepsia published up until 31 July 2023. The quality of these studies was evaluated using the Cochrane Risk of Bias assessment tool. The analysis of data was performed using the software RevMan 5.4. The total clinical effectiveness rate was evaluated as the primary outcome. In addition, gastric emptying rate, symptom score and safety evaluation were evaluated as the secondary outcomes. Results: The meta-analysis included 23 studies, involving 2,101 individuals. Xiangsha liujunzi decoction demonstrated a significantly higher clinical effectiveness rate compared to the control group (RR 1.27; 95% CI 1.21, 1.33; p < 0.00001). Moreover, it exhibited superior gastric emptying rate and symptom score improvement compared to the control group. Nevertheless, no remarkable differences were detected in safety between Xiangsha liujunzi decoction and the control group (RR 0.67; 95% CI 0.16, 2.76; p = 0.58). Conclusion: The findings of this study suggest that Xiangsha liujunzi decoction exhibits effectiveness and no significant adverse events observed. However, because of the low quality of the enrolled studies, more high-quality and strict design randomized controlled trials are required in the future.
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To address our climate emergency, "we must rapidly, radically reshape society"-Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross-government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much-needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science.
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Jinmao Jiedu granule is a Chinese medicine preparation consisting of Actinidia valvata Dunn, Salvia chinensis Benth, Iphigenia indica Kunth, and chicken gizzard. For many years, it has been employed in adjuvant therapy for cancer, especially liver cancer. However, the potential toxicity of the granule has not been reported. The present study aimed to assess the repeated-dose toxicity of orally administered Jinmao Jiedu granules for Sprague-Dawley (SD) rats. SD rats were orally administered Jinmao Jiedu granules at doses of 2.85, 5.70, and 11.40 g/kg in a 28-day subchronic toxicity study. No adverse clinical signs associated with treatment were noted throughout the experiment. There were no treatment-related toxicity alterations in body weight, hematology, clinical biochemistry, urinalysis, necropsy, and histopathology in rats compared with the control group. The No Observed Adverse Effect Level (NOAEL) of the Jinmao Jiedu granule was higher than 11.40 g/kg/day in rats.
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Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/toxicidad , Medicamentos Herbarios Chinos/administración & dosificación , Ratas , Masculino , Administración Oral , Femenino , Nivel sin Efectos Adversos Observados , Peso Corporal/efectos de los fármacos , Pruebas de Toxicidad Subcrónica , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Lung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Proteínas de Neoplasias , Células Madre Neoplásicas , Fenotipo , Receptor ErbB-2 , Animales , Humanos , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Línea Celular Tumoral , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , FemeninoRESUMEN
In the quasi-two-dimensional superconductor NbSe2, the superconducting transition temperature (Tc) is layer-dependent, decreasing by about 60% in the monolayer limit. However, for the extremely anisotropic copper-based high-Tc superconductor Bi2Sr2CaCu2O8+δ (Bi-2212), the Tc of the monolayer is almost identical with that of its bulk counterpart. To clarify the effect of dimensionality on superconductivity, here, we successfully fabricate ultrathin flakes of iron-based high-Tc superconductors CsCa2Fe4As4F2 and CaKFe4As4. It is found that the Tc of monolayer CsCa2Fe4As4F2 (after tuning to the optimal doping by ionic liquid gating) is about 20% lower than that of the bulk crystal, while the Tc of three-layer CaKFe4As4 decreases by 46%, showing a more pronounced dimensional effect than that of CsCa2Fe4As4F2. By carefully examining their anisotropy and the c-axis coherence length, we reveal the general trend and empirical law of the layer-dependent superconductivity in these quasi-two-dimensional superconductors.
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Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.
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Cumarinas , Proteína Forkhead Box O1 , Glutatión , Factor 2 Relacionado con NF-E2 , FN-kappa B , Estrés Oxidativo , Síndrome del Ovario Poliquístico , Especies Reactivas de Oxígeno , Transducción de Señal , Animales , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Femenino , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Cumarinas/farmacología , Cumarinas/uso terapéutico , FN-kappa B/metabolismo , Proteína Forkhead Box O1/metabolismo , Transducción de Señal/efectos de los fármacos , Glutatión/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Células de la Granulosa/metabolismo , Células de la Granulosa/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
Objective: To study the current status of hemophilia B (HB) patients in the central and western regions of China. Methods: This cross-sectional, multicenter study was conducted in seven provinces in the central and western regions of China from April 2019 to June 2023. Samples were collected for the factor IX activity, inhibitor screen, and gene mutation. Furthermore, the status of six index joints and quality of life (QoL) were assessed. Results: A total of 185 HB patients (mild 15, moderate 75, and severe 95) with a median age of 12.17 years were enrolled. 30.3% (56/185) of patients had a family history of HB. 34.6% (64/185) of HB patients had diagnostic delay and 38.5% (69/179) experienced treatment delay. The incidence of inhibitors was 6.1% (11/179). We identified 123 genetic variants in this study, with missense mutations being the most common. 84.0% (89/106) of HB mothers were genetically identified as carriers, with 27.7% (13/47) of carriers having clotting factor levels less than 0.40â IU/ml. 71.4% (132/185) of HB patients had a history of joint hemorrhage, with a rate of target joint in these patients was 64.4% (85/132). Lower extremity joints were most often affected in patients. The Hemophilia Joint Health Score (HJHS) score was significantly positively correlated with the Hemophilia Early Arthropathy Detection with Ultrasound in China (HEAD-US-C) (r = 0.542, P < 0.001). Patients who received prevention treatment, inhibitor negative, without treatment delay, and without high-intensity replacement therapy showed a higher total score of the short form-36 health survey (SF-36). Conclusions: One-third of HB patients had delay in diagnosis and treatment, and the incidence of inhibitors was 6.1%. Target joints were present in nearly half of HB patients. Missense was the main mutation type. 84.0% of mothers of HB patients in this study were found to be carriers. HEAD-US-C and HJHS can complement each other in the evaluation of joint status and give a valid basis for early clinical management. Early detection and preventive treatment, as well as reducing high-intensity replacement therapy and inhibitor generation, can effectively improve the QoL of patients.
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INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Análisis de la Aleatorización Mendeliana , Fenotipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/inmunología , Receptores CCR2/genética , Linfocitos T CD8-positivos/inmunología , Antígenos CD28/genéticaRESUMEN
BACKGROUND: Regulatory actions are increasingly used to tackle issues such as excessive alcohol or sugar intake, but such actions to reduce sedentary behaviour remain scarce. World Health Organization (WHO) guidelines on sedentary behaviour call for system-wide policies. The Chinese government introduced the world's first nation-wide multi-setting regulation on multiple types of sedentary behaviour in children and adolescents in July 2021. This regulation restricts when (and for how long) online gaming businesses can provide access to pupils; the amount of homework teachers can assign to pupils according to their year groups; and when tutoring businesses can provide lessons to pupils. We evaluated the effect of this regulation on sedentary behaviour safeguarding pupils. METHODS: With a natural experiment evaluation design, we used representative surveillance data from 9- to 18-year-old pupils before and after the introduction of the regulation, for longitudinal (n = 7,054, matched individuals, primary analysis) and repeated cross-sectional (n = 99,947, exploratory analysis) analyses. We analysed pre-post differences for self-reported sedentary behaviour outcomes (total sedentary behaviour time, screen viewing time, electronic device use time, homework time, and out-of-campus learning time) using multilevel models, and explored differences by sex, education stage, residency, and baseline weight status. RESULTS: Longitudinal analyses indicated that pupils had reduced their mean total daily sedentary behaviour time by 13.8% (95% confidence interval [CI]: -15.9 to -11.7%, approximately 46 min) and were 1.20 times as likely to meet international daily screen time recommendations (95% CI: 1.01 to 1.32) one month after the introduction of the regulation compared to the reference group (before its introduction). They were on average 2.79 times as likely to meet the regulatory requirement on homework time (95% CI: 2.47 to 3.14) than the reference group and reduced their daily total screen-viewing time by 6.4% (95% CI: -9.6 to -3.3%, approximately 10 min). The positive effects were more pronounced among high-risk groups (secondary school and urban pupils who generally spend more time in sedentary behaviour) than in low-risk groups (primary school and rural pupils who generally spend less time in sedentary behaviour). The exploratory analyses showed comparable findings. CONCLUSIONS: This regulatory intervention has been effective in reducing total and specific types of sedentary behaviour among Chinese children and adolescents, with the potential to reduce health inequalities. International researchers and policy makers may explore the feasibility and acceptability of implementing regulatory interventions on sedentary behaviour elsewhere.
Asunto(s)
Conducta Sedentaria , Humanos , Adolescente , Masculino , Femenino , Niño , China , Estudios Transversales , Tiempo de Pantalla , Juegos de Video , Promoción de la Salud/métodos , Conducta del Adolescente , Estudios Longitudinales , Ejercicio Físico , Estudiantes , Conducta Infantil/psicología , Instituciones AcadémicasRESUMEN
The objective of the study is to determine the causal relationship and potential mechanisms between Parkinson's disease (PD) and neuroinflammatory and neurotoxic mediators. We conducted two-sample Mendelian randomization (2SMR) study and multivariable Mendelian randomization (MVMR) analysis to investigate the causality between PD and neuroinflammatory and neurotoxic mediators. The mediation analysis with MR was also conducted to determine the potential mediating effect of neuroinflammatory and neurotoxic mediators between asthma and PD. Genetically predicted levels of nine neuroinflammation were associated with changes in PD risk. The associations of PD with CCL24, galectin-3 levels, haptoglobin, and Holo-Transcobalamin-2 remained significant in multivariable analyses. The mediation analysis with MR revealed that asthma affects PD through CCL24 and galectin-3. The results showed neuroinflammation could affect the pathogenesis of PD. In the combined analysis of these nine variables, CCL24, galectin-3 levels, HP, and Holo-Transcobalamin-2 alone were found to be significant. Asthma plays an intermediary role through CCL24 and galectin-3 levels.