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BACKGROUND: The long-term follow-up of asymptomatic intracranial hemorrhage (aICH) in patients with acute ischemic stroke after endovascular treatment (EVT) remains controversial.ObjectiveTo evaluate the potential effect of aICH in a real-world practice setting using a matched prospective database. METHODS: This observational cohort study enrolled patients between January 2015 and December 2022 in a prospective database. Eligible patients with occlusions in the anterior circulation were given endovascular treatment and achieved successful reperfusion. The primary outcome was functional independence (modified Rankin Scale (mRS) score 0-2). Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: 732 patients, 516 without any ICH and 216 with aICH, were included. 418 and 348 patients were identified after matching in the aICH substudy and hemorrhagic infarction type aICH substudy, respectively. In the postmatched population, patients with aICH had worse functional outcomes (mRS score 0-2) at 90 days than patients without any ICH (37.8% vs 55.5%: P<0.001). Worse functional outcomes were seen in patients with aICH who were older (OR=5.59 (95% CI 2.91 to 10.74)), had higher baseline National Institutes of Health Stroke Scale score (OR=6.80 (95% CI 3.72 to 12.43)), lower baseline Alberta Stroke Program Early CT Score (OR=2.08 (95% CI 1.23 to 3.51)), and who received general anesthesia (OR=3.37 (95% CI 1.92 to 5.90)). CONCLUSIONS: This matched-control study largely confirmed that asymptomatic ICH after EVT is associated with worse functional outcomes, and the harmful effect is more significant in older patients and those with severe baseline clinical and radiological features.
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Congenital joint synostosis (CJS) is a functional impairment resulting from failure in joint morphogenesis during embryonic development. Clinically, it may be classified as syndromic (sCJS) and non-syndromic (nsCJS) disorders. Common sCJS include chromosomal disorders such as Klinefelter syndrome and single-gene disorders like Apert/Pfeiffer/Crouzon syndromes, Holt-Oram syndrome, Ehlers-Danlos syndrome, and Radial-ulnar synostosis with thrombocytopenia, presenting with multiple system/organ anomalies. By contrast, nsCJS manifest with only joint abnormalities, affecting one or multiple joints. This review has focused on human nsCJS and its genetic etiology. To date, variants in seven genes (NOG, GDF5, FGF9, GDF6, FGF16, SMAD6, and MECOM) have been identified as causative factors for nsCJS. This review has focused on such genes and provided a comprehensive review for the clinical phenotypes, genetic patterns, common variants, and underlying mechanisms associated with nsCJS based on a literature review. In addition, it has also analyzed other candidate genes for nsCJS within the context of relevant signaling pathways involved in joint morphogenesis.
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Sinostose , Humanos , Sinostose/genética , Fator 5 de Diferenciação de Crescimento/genética , Articulações/anormalidades , Articulações/embriologiaRESUMO
Organophosphate esters (OPEs) pose hazards to both humans and the environment. This study applied target screening to analyze the concentrations and detection frequencies of OPEs in the soil and groundwater of representative contaminated sites in the Pearl River Delta. The clusters and correlation characteristics of OPEs in soil and groundwater were calculated by self-organizing map (SOM). The risk assessment and partitions of OPEs in industrial park soil and groundwater were conducted. The results revealed that 14 out of 23 types of OPEs were detected. The total concentrations (Σ23OPEs) ranged from 1.931 to 743.571 ng/L in the groundwater, and 0.218 to 79.578 ng/g in the soil, the former showed highly soluble OPEs with high detection frequencies and concentrations, whereas the latter exhibited the opposite trend. SOM analysis revealed that the distribution of OPEs in the soil differed significantly from that in the groundwater. In the industrial park, OPEs posed acceptable risks in both the soil and groundwater. The soil could be categorized into Zone I and II, and the groundwater into Zone I, II, and III, with corresponding management recommendations. Applying SOM to analyze the characteristics and partitions of OPEs may provide references for other new pollutants and contaminated sites.
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Biomechanic studies can provide a powerful theoretical and scientific basis for studies on knee osteoarthritis (OA), which is of great significance for clinical management as it provides new concepts and methods in clinical and research settings. This study aimed to discuss and summarize biomechanical research on lower extremities in individuals with knee OA in the past ten years. The methodology of this review followed the framework outlined in the Joanna Briggs Institute (JBI) guidelines and strictly followed the checklist for drafting the findings. A literature search was conducted using PubMed, Scopus, Cochrane Library, Embase, Web of Science, Grey literature search in Open Library, and Google Academic databases. Relevant literature was searched from 2011 to 2023. Sixteen studies were included in this scoping review. Biomechanical research on knee OA in the last decade demonstrates that the biomechanics of the hip, knee, and ankle have a profound influence on the pathogenesis and treatment of knee OA. Individuals with knee OA have biomechanical changes in hip, knee, and ankle joints such as a significant defect in the strength of ankle varus muscles, weakness of hip abductor muscle, walking with toes outwards, increased knee adduction moment and angle, and decreased knee extensor moment. As the severity of knee OA increases, the tendency of hip abduction positions also increases. Further research with a longitudinal study design should focus on the determination of the relative importance of different biomechanical and neuromuscular factors in the development and progression of the disease.
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The non-coordination between the socio-economic systems and ecosystems of a region is a crucial obstacle to sustainable development. To reveal the relationships between complex urban systems and achieve the goal of sustainable and coordinated urban development, we constructed a coupling coordination degree model (CCDM) and coupling angle model (CAM) and analyzed the degree of coupling coordination and evolution process among the population, water resources, economy, and ecology (PWEE) system of the Tuha region for 2005-2020. The results indicated that: (1) During 2005-2020, the comprehensive development index (CDI) of the population, water resources and economy subsystems was 0.21-0.65, with the three subsystems portraying an overall increase; the average values of the RSEI at five-year intervals were 0.29, 0.28, 0.28, and 0.26, indicating a downward trend in the environmental quality. (2) The coupling coordination effect of the PWEE system portrayed a low level; the coupling coordination degree (CCD) values were 0.28-0.58, portraying a fluctuating upward trend. The level of CCD increased from low disorder to marginal coordination. (3) The PWEE system's scissor difference reflects large evolutionary characteristics. The ecological support capacity was not observed until the late stage. We conclude that the PWEE composite system of the region is in a stage of disordered development. These findings significantly bolster the theoretical underpinnings of sustainable development studies, offering essential scientific theories and methodological frameworks for crafting sustainable development policies tailored to urban systems in the Tuha region.
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The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.
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Pesquisa Biomédica , Animais , Pesquisa Biomédica/tendências , Tupaiidae , Modelos Animais de Doenças , Tupaia , Modelos AnimaisRESUMO
Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children, characterized by age-inappropriate inattention, hyperactivity, and impulsivity, which can cause extensive damage to children's academic, occupational, and social skills. This review will present current advancements in the field of attention deficit hyperactivity disorder, including genetics, environmental factors, epigenetics, and neuroimaging features. Simultaneously, we will discuss the highlights of promising directions for further study.
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BACKGROUND: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear. METHODS: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration. RESULTS: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1ß, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice. CONCLUSIONS: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.
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Camundongos Knockout , Sirtuínas , Cicatrização , Animais , Cicatrização/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Sirtuínas/deficiência , Camundongos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/genética , Inflamação/patologia , Inflamação/metabolismo , MasculinoRESUMO
Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors, many innate immune and local apoptosis related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early ß-amyloid pathology. But microglia are not involved in synapse loss at late ß-amyloid stages. Phagocytic microglia also engulfment synapses in complement dependent way in schizophrenia, anxiety and stress. Besides, phagocytic astrocytes engulf synapses in a MEGF10 dependent way during visual development, memory and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminating excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.
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Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3ß, p-GSK-3ß, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3ß/GSK-3ß. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3ß pathway and promotion of MAP2 expression.
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Glicogênio Sintase Quinase 3 beta , Proteínas Associadas aos Microtúbulos , Fármacos Neuroprotetores , Proteínas Proto-Oncogênicas c-akt , Sevoflurano , Transdução de Sinais , Peixe-Zebra , Animais , Sevoflurano/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Apoptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Pós-Condicionamento Isquêmico/métodos , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/patologia , Proteínas de Peixe-Zebra/metabolismo , Modelos Animais de Doenças , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , MasculinoRESUMO
BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.
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Neoplasias , Pênfigo , Pênfigo/epidemiologia , Humanos , Prevalência , Incidência , Neoplasias/epidemiologia , Neoplasias/complicações , Europa (Continente)/epidemiologia , América do Norte/epidemiologia , Ásia/epidemiologiaRESUMO
PURPOSE: To investigate the effects of positive airway pressure (PAP) device on urinary albumin to creatinine ratio (UACR) and metabolic indexes in patients with metabolic syndrome (MS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: This study is a retrospective cohort study. Grouped according to whether to use PAP treatment, there were 25 cases in the PAP group and 44 cases in the no OSAHS treatment group. The PAP group received positive airway pressure device and routine treatment of MS. The no OSAHS treatment group received routine treatment of OSAHS and MS. The treatment period is 3 months. RESULTS: 1. The PAP group demonstrated significant reductions in Body Mass Index (BMI), Waist circumference (WC), Neck circumference (NC), Visceral fat area (VFA), Fasting C peptide (FCP), high-sensitivity C-reactive protein (hs-CRP), and UACR compared to the no OSAHS treatment group, with significant differences (P all <0.05). Among them, the UACR in the PAP group decreased significantly (from 86.05(52.55,131.61)mg/g to 16.76(8.70,25.12)mg/g, P<0.001). 2. Linear regression analysis using the decrease in UACR values as the dependent variable demonstrated a positive linear relationship with the decrease in BMI, VFA, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR). Furthermore, multiple linear regression analysis indicated that the decrease in VFA (B=0.537 [95% confidence interval, 0.084 to 0.989]; P = 0.021) and HOMA-IR (B=1.000 [95% confidence interval, 0.082 to 1.917]; P = 0.033) values independently correlated with decrease in UACR values. CONCLUSIONS: PAP treatment can reduce UACR in patients with MS and OSAHS, and has the effect of improving metabolic disorders. The decrease of UACR in patients may be related to the decrease of visceral fat and the improvement of insulin resistance.
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Síndrome Metabólica , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome Metabólica/terapia , Adulto , Creatinina/sangue , Creatinina/urina , Pressão Positiva Contínua nas Vias Aéreas , Estudos de Coortes , Índice de Massa CorporalRESUMO
River sediments play a critical role in sustaining deltaic wetlands. Therefore, concerns are raised about wetlands' fate due to the decline of river sediment supply to many deltas. However, the dynamics and drivers of suspended sediment near deltaic coasts are not comprehensively assessed, and its response to river sediment supply changes remains unclear. Here we examine patterns of coastal suspended sediment concentration (SSC) and river sediment plume area (RPA) for 349 deltas worldwide using satellite images from 2000 to 2020. We find a global increase in SSC and RPA, averaging +0.46% and +0.48% yr-1, respectively, with over 59.0% of deltas exhibiting an increase in both SSC and RPA. SSC and RPA increases are prevalent across all continents, except for Asia. The relationship between river sediment supply and coastal SSCs varies between deltas, with as much as 45.2% of the deltas showing opposing trends between river sediments and coastal SSCs. This is likely because of the impacts of tides, waves, salinity, and delta morphology. Our observed increase in SSCs near river delta paints a rare promising picture for wetland resilience against sea-level rise, yet whether this increase will persist remains uncertain.
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Background: ANXA2 has been extensively documented in relation to cancer. Nevertheless, the involvement of ANXA2 in lung carcinoma remains uncertain. Methods: Data from The Cancer Genome Atlas (TCGA) database was downloaded using open-access methods. The examination of publicly available data was conducted utilizing the R software. The mRNA level of specific molecules was detected using Real-time Quantitative PCR (qPCR). The protein level of specific molecules was detected using the Western blot assay. The cell proliferation ability of cancer cells was assessed using the CCK8 assay. The invasion and migration capability of cancer cells was assessed using the Transwell assay. Validation of exosomes extraction was conducted using electron microscopy and particle size analysis. Results: In this study, based on series experiments, we found that ANXA2 can promote the activation of neuroastrocytes cells CP-H122 through the exosome pathway. Also, we found that ANXA2 can be transmitted from A549 cells to CP-H122 through the exosomes pathway and further promote the activation of CP-H122. Activated CP-H122 cells further enhance the proliferation, invasion and metastasis of A549 cells. Meanwhile, we performed transcriptome sequencing to explore the downstream genes of ANXA2 to screen potential targets for follow-up studies. Analysis based on public data showed that ANXA2 was related to the worse survival performance and clinical features of lung cancer. Gene set enrichment analysis based on the Hallmark gene set indicated that the patient with high ANXA2 expression might have a higher activity of the apical surface, reactive oxygen species pathway, angiogenesis, TGF-ß signaling, MYC target, but lower activity of pancreas-ß cells. More important, our results showed that ANXA2 can affects immunotherapy response and reshape immune microenvironment of lung cancer. Conclusions: This study demonstrates that ANXA2 activates CP-H122 cells, affects A549 cell behavior, and impacts lung cancer prognosis and immunotherapy response.
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Northwest China has great natural resource endowment to develop its economy, but factors such as geographic remoteness and technological backwardness result in lower economic levels and higher carbon emissions. This study calculated the energy-related carbon emissions of five provinces in this region, and the evolutionary characteristics of energy-related carbon emissions were analysed from the spatiotemporal perspective. The Kaya identity was applied to decompose the factors influencing energy-related carbon emissions, and the logarithmic mean divisia index (LMDI) and refined Laspeyres index were combined to calculate the role of each influencing factor on energy-related carbon emissions. Finally, the Tapio and LMDI models were used to analyse the evolution of the decoupling relationship between energy-related carbon emissions and economic growth and the role of various influencing factors. The energy-related carbon emissions in Northwest China showed an increasing trend. In terms of influencing factors, economic growth and urban expansion had the highest contributions to carbon emissions and decoupling inhibition, whereas population agglomeration had the opposite effect. Northwest China showed great decoupling trends between energy-related carbon emissions and economic growth.
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Bacterial infected wounds, which is characterized by easy infection, multiple inflammation and slow healing, is a complex symptom, resulting from metabolic disorder of the wound microenvironment. In this study, a series of self-healing double-network hydrogels based on KGRT peptide (Lys-Gly-Arg-Thr) with antibacterial, anti-inflammatory and optimizing cellular functions were designed to promote the healing of infected wounds with full-thickness skin defects. Moreover, the dextran hydrogelintroduces a large number of side chains, which are entangled with each other in the Schiff base network to form an interpenetrating structure. The hydrogel might regulate cell metabolism, differentiation and vascular endothelial growth factor (VEGF) function. Importantly, both in vitro and in vivo data showed that hydrogel not only has good antibacterial properties (99.8 %), but also can eradicate bacterial biofilm, effectively reduce inflammation (down-regulated IL-1ß, TNF-α and ROS) and accelerate chronic wound healing process by speeding-up wound closure, increasing granulation tissue thickness, collagen deposition, angiogenesis (up-regulated CD31). The hydrogel could up-regulate mRNA expression of PI3K, AKT, ERK, eNOS, HIF-1α and VEGF, which were correlated with wound healing. Consistently, the hydrogel could promote infected wounds healing and inhibit inflammation through ERK/eNOS signaling pathway. Collectively, hydrogel has excellent clinical application potential for promoting infected wound healing.
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Hidrogéis , Fator A de Crescimento do Endotélio Vascular , Humanos , Hidrogéis/farmacologia , Transdução de Sinais , Cicatrização , Peptídeos , Antibacterianos/farmacologia , InflamaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.
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Psoríase , Dermatopatias , Animais , Camundongos , Psoríase/patologia , Pele , Queratinócitos , Dermatopatias/metabolismo , Imiquimode , Proliferação de Células , Hiperplasia/patologia , Apoptose , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
BACKGROUND: The increasing prevalence of childhood obesity has become an urgent public health problem, evidence showed that intervention for childhood obesity bring enormous health benefits. However, an effective individualized intervention strategy remains to be developed, and the accompanying remission of related complications, such as nonalcoholic fatty liver disease (NAFLD), needs to be assessed. This study aimed to develop an m-Health-assisted lifestyle intervention program targeting overweight/obese children and assess its effectiveness on indicators of adiposity and NAFLD. METHODS: This is a cluster-randomized controlled trial that conducted in children with overweight/obesity in Ningbo city, Zhejiang Province, China. Students in Grade 3 (8-10 years old) were recruited from six primary schools, with three be randomized to intervention group and three to usual practice group. The intervention program will last for one academic year and consists of health education, dietary guidance, and physical activity reinforcement. This program is characterized by encouraging four stakeholders, including School, Clinic, famIly, and studENT (SCIENT), to participate in controlling childhood obesity, assisted by m-Health technology. Assessments will be conducted at baseline and 3 months, 9 months, 24 months, and 36 months after baseline. The primary outcome will be the differences between the two groups in students' body mass index and fatty liver index at the end of the intervention (9 months after baseline). During the implementation process, quality control methods will be adopted. DISCUSSION: The program will test the effectiveness of the m-Health-assisted lifestyle intervention on children with obesity and NAFLD. The results of this study will provide evidence for establishing effective lifestyle intervention strategy aimed at childhood obesity and NAFLD and may help develop guidelines for the treatment of obesity and NAFLD in Chinese children. TRIAL REGISTRATION: Clinicaltrials.gov NCT05482191. Registered on July 2022.
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Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Criança , Humanos , Obesidade Infantil/diagnóstico , Obesidade Infantil/terapia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Sobrepeso , Estilo de Vida , Índice de Massa Corporal , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The launch of the national carbon emissions trading market in China is a policy to carry out the Beautiful China initiative and to establish a low-carbon economic development system that promotes carbon emission and waste reduction. In order to detect the carbon metabolic processes of the pilot and nonpilot municipalities or provinces in the northern region of Chinaï¼ the theory of urban carbon metabolism and the methods of input-output analysis and ecological network analysis were introduced and used. The results showed that the direct carbon emissions of Beijing and Tianjin had decreasedï¼ but their embodied carbon emissions had increased since 2012. The direct and embodied carbon emissions of the pilot sectors in Beijing and Tianjin had the same trendï¼ specificallyï¼ the emissions of the sectors of mining and washing of coalï¼ extraction of petroleum and natural gasï¼ and manufacture of non-metallic mineral products decreased significantlyï¼ but the sectors of production and supply of electric power and steam with high carbon emission increased. The same trend of the embodied carbon emission intensities of sectors with that of their embodied carbon emissions verified that the embodied added values were not growing with the promotion of the carbon emission trading market. Subsequentlyï¼ the embodied carbon emission of the pilot sectors in all the municipalities and provinces of the northern region were all contributed mainly by the emissions embodied by a path length less than 6ï¼ thereforeï¼ it showed that more attention should be paid to the trade among sectors with a path length less than 6 and reducing their carbon emissions. Furthermoreï¼ from 2007 to 2012ï¼ products or service trading among sectors mostly concentrated on sectors within one municipality or provinceï¼ and these products or services had the characteristics of low carbon emission. Since 2012ï¼ the integration development of the Beijing-Tianjin-Hebei urban agglomeration and the new regional economic patterns established in the northern region both promoted the trading across provinces and across sectors. This research is based on the background of the carbon emission trading policy and aims to build a methodology to identify the key actors and paths in a metabolic system. This could provide a scientific basis for regional policy implementation and regional long-term sustainable development.