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BACKGROUND: The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. METHODS: We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. RESULTS: During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long'an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast-northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west-north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. CONCLUSIONS: The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Síndrome de Inmunodeficiencia Adquirida/epidemiología , VIH , Prevalencia , China/epidemiologíaRESUMEN
The study aimed to establish a machine learning-based scoring nomogram for early recognition of likely pressure injuries in an intensive care unit (ICU) using large-scale clinical data. A retrospective cohort study design was employed to develop and validate a top-performing clinical feature panel accessibly in the electronic medical records (EMRs), which was in the mode of a quantifiable nomogram. Clinical factors regarding demographics, admission cause, clinical laboratory index, medical history and nursing scales were extracted as risk candidates. The performance improvement was based on the application of the machine learning technique, comprising logistic regression, decision tree and random forest algorithm with five-fold cross-validation (CV) technique. The comprehensive assessment of sensitivity, specificity and the area under the receiver operating characteristic curve (AUROC) was considered in the evaluation of predictive performance. The receiver operating characteristic curves revealed the top performance for the logistic regression model in respect to machine learning improvement, achieving the highest sensitivity and AUC among three types of classifiers. Compared against the 23-point Braden scale routinely recorded online, an incorporated nomogram of logistic regression model and Braden scale achieved the best performance with an AUC of 0.87 ± 0.07 and 0.84 ± 0.05 in training and test cohort, respectively. Our findings suggest that the machine learning technique potentiated the limited predictive validity of routinely recorded clinical data on pressure injury development during ICU hospitalisation. Easily accessible electronic records held the potentials to substitute the traditional Braden score in the prediction of pressure injury in intensive care unit. Preoperative prediction of pressure injury facilitates the exemption from the severe consequences.
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Unidades de Cuidados Intensivos , Aprendizaje Automático , Úlcera por Presión , Humanos , Algoritmos , Registros Electrónicos de Salud , Estudios RetrospectivosRESUMEN
AIMS: The objective of the present study was to elucidate the effects of sulfur (S) application on selenium (Se) uptake and seed Se speciation in high-protein soybean (Glycine max L.) grown in different soil types. METHODS: Pot experiments were conducted with soybean plants grown in yellow-brown soil (pH 5.68) and in calcareous alluvial soil (pH 7.87). Sodium selenate (Na2SeO4, 2 mg kg-1) was applied to soil with or without S fertilizer (S, 100 mg kg-1). RESULTS: Soybean grain yield and total biomass in calcareous alluvial soil were both approximately 1.3-fold the levels in yellow-brown soil. Following Se application, seed Se concentration in calcareous alluvial soil was 3.2-fold the concentration in yellow-brown soil, although additional S application reduced the corresponding seed Se concentrations by 55.6% and 38.6%, respectively. Generally, Se application facilitated Se translocation and enrichment in soybean seeds. Organic Se accounted for 92% of seed total Se and Se-methionine (>90%) was always the major Se species. Available Se (soluble and exchangeable fractions) accounted for 50.7% (yellow-brown soil) and 70.1% (calcareous alluvial soil) of soil total Se under Se treatment, while additional S application decreased the corresponding proportion of soluble Se by 12.6% and 14.4%. CONCLUSIONS: The bioavailability of selenate in calcareous alluvial soil was higher than the bioavailability in yellow-brown soil and was more negatively affected by S application. Although S application inhibited Se uptake in soybean plants in both soil types, it did not influence seed Se speciation and Se-methionine was the major Se species.
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Glycine max/fisiología , Selenio/metabolismo , Contaminantes del Suelo/metabolismo , Azufre/análisis , Disponibilidad Biológica , Transporte Biológico , Grano Comestible/química , Fertilizantes/análisis , Semillas/química , Ácido Selénico , Selenometionina , Suelo , Contaminantes del Suelo/análisisRESUMEN
In this paper, we aim at the problem that MIMO radar's target detection performance is greatly reduced in the complex multi-signal-dependent interferences environment. We propose a joint design method based on semidefinite relaxation (SDR), fractional programming and randomization technique (JD-SFR) and a joint design method based on coordinate descent (JD-CD) to solve the actual transmit waveform and receive filter bank directly to reduce the loss of strong interference to the output signal-to-interference-plus-noise ratio (SINR) of the radar system. Therefore, the maximization of output SINR is taken as the criterion of the optimization problem. The designed waveforms take into account the radar transmitter's hardware requirements for constant envelope waveforms and impose similarity constraints on the waveforms. JD-SFR uses SDR, fractional programming and randomization technique to deal with the non-convex optimization problems encountered in the solution process. JD-CD transforms the optimization problem into a function of the phase of the waveform and then solves the transmit waveform based on CD. Compared with other methods, the proposed method has lower output SINR loss under strong power interference and forms deep nulls on the direction beampattern of multiple interference sources, which indicates that it has better anti-interference performance.
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RadarRESUMEN
The pathogenesis of cardiorenal syndrome (CRS) is very complex, and currently there is no effective treatment for CRS. Higenamine (HI) has been shown to improve cardiac function in rats with heart failure. However, the role of higenamine in CRS remains unknown. Here, in vitro, higenamine treatment markedly reduced neonatal rat cardiac fibroblast collagen synthesis and inhibited neonatal rat cardiac myocyte hypertrophy. In our study, a rat model of type 2 CRS was induced by left anterior descending coronary artery ligation combined with 5/6 subtotal nephrectomy (STNx). Higenamine treatment decreased serum creatinine (Scr), blood urea nitrogen, and brain natriuretic peptide levels and was capable of improving left ventricular remodeling and systolic function in CRS rats, accompanied with decreased expression of transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA) and collagen I (Col1A1). Moreover, higenamine significantly inhibited the protein expression of phosphorylated apoptosis signal-regulated kinase 1 (p-ASK1) and downstream mitogen-activated protein kinases (MAPK) (ERK, P38)/NF-κB in cardiorenal tissues of CRS rats and neonatal rat cardiac fibroblast/neonatal rat cardiac myocyte cells. Our study demonstrated that higenamine improved cardiorenal function in CRS rats and attenuated heart and kidney fibrosis possibly via targeting ASK1/MAPK (ERK, P38)/NF-κB signaling pathway. This finding extends our knowledge on the role of higenamine in cardiorenal fibrosis, providing a potential target to prevent the progression of CRS.
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Alcaloides/farmacología , Síndrome Cardiorrenal/tratamiento farmacológico , Colágeno/biosíntesis , Fibroblastos/efectos de los fármacos , Riñón/efectos de los fármacos , MAP Quinasa Quinasa Quinasa 5/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Tetrahidroisoquinolinas/farmacología , Animales , Síndrome Cardiorrenal/enzimología , Síndrome Cardiorrenal/patología , Células Cultivadas , Modelos Animales de Enfermedad , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fibroblastos/enzimología , Fibroblastos/patología , Fibrosis , Riñón/enzimología , Riñón/patología , Masculino , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , FN-kappa B/metabolismo , Fosforilación , Ratas Sprague-Dawley , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Dioecy is a rare sexual system that is thought to represent an "evolutionary dead end". While many studies have addressed the evolution of dioecy and/or its relationship with the evolution of the woody habit, few have explored the relationship between dioecy and climbing habit, and their effects on diversification rates. Here, we study the evolution of sexual systems and growth habit in Mussaenda (Rubiaceae) using a robust phylogeny of the genus based on eight plastid regions and a broad sampling of taxa (92 of the 132 species were sampled). A time-calibrated tree was constructed to estimate diversification rates in different clades and its correlates with focal characters. More specifically, we assess evolutionary correlations between dioecy and climbing habit and their respective influences on diversification rates. Ancestral character state reconstructions revealed that distyly is the most likely ancestral state in Mussaenda. Distyly has subsequently given rise to dioecy, short-styled floral monomorphism, and long-styled floral monomorphism. Dioecy has evolved independently at least four times from distyly, and has reversed to homostylous hermaphroditism at least twice, which does not support the "evolutionary dead end" hypothesis. A significant correlation between the evolution of dioecy and climbing growth form was found in Mussaenda. It is possible that a strong association between high net diversification rates and dioecy may exist in Mussaenda, but no association was found with climbing habit.
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Evolución Biológica , Rubiaceae/clasificación , Rubiaceae/crecimiento & desarrollo , Biodiversidad , Modelos Teóricos , Filogenia , Probabilidad , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the significance of flexible bronchoscopy in children with respiratory diseases. METHODS: A retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage. RESULTS: Bronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment. CONCLUSIONS: Flexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.
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Broncoscopía/métodos , Enfermedades Pulmonares/diagnóstico , Broncoscopía/efectos adversos , Niño , Preescolar , Tos/diagnóstico , Femenino , Humanos , Lactante , Masculino , Neumonía por Mycoplasma/diagnóstico , Ruidos Respiratorios/diagnóstico , Estudios RetrospectivosRESUMEN
BACKGROUND Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death in adults. Despite recent advances in the clinical technologies, the screening and diagnostic efficacy for HCC remains poor. Discovering novel and reliable HCC biomarkers is urgently needed. MATERIAL AND METHODS We performed a transcriptome-proteome integrated assay to track the possible HCC biomarkers from the process of HCC-derived gene expression in malignant cells to its protein product released into serum. RESULTS Our screening results demonstrated that heat shock protein 90A (HSP90A), which participates in the PI3K-Akt signaling pathway and many other cancer-related pathways, warrants further investigation. The expression of HSP90A was increased in the HCC cells, serum, and tissues. Immunohistochemistry analysis on 76 clinical tissue samples also suggested the relevance between HSP90A expression and HCC metastatic behavior. CONCLUSIONS These findings suggest a role for HSP90A in HCC pathogenesis and the potential use of HSP90A for the screening and diagnosis of this malignancy.
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Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Proteínas HSP90 de Choque Térmico/genética , Neoplasias Hepáticas/genética , Adulto , Anciano , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Proteínas HSP90 de Choque Térmico/sangre , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteoma/metabolismo , Proteómica , Transducción de SeñalRESUMEN
Background: Exchange transfusion therapy is a complex and invasive procedure with a high risk coefficient. This method involves replacing the entire blood of a child with fresh blood with double circulating blood volume in a short period, typically in 1-2â h. This procedure can cause the body's internal environment to be unstable, which can put newborns under a lot of stress. This stress can lead to many, including abnormal laboratory biochemical examination, low or high blood pressure, and apnea. There is also the possibility of secondary infection and, in severe cases, cardiac arrest. This study investigated the effects of Humidified high-flow nasal cannula (HHFNC) ventilation on hemodynamic stability and oxygenation during exchange transfusion in neonates. Furthermore, the effects on brain metabolism and salivary cortisol during exchange transfusion were also analyzed. Methods: In this study, the control group consisted of 45 cases of children who underwent simple blood exchange between 1 May 2017, and 31 December 2019 control group. The observation group consisted of 33 cases of children who underwent blood exchange under HHFNC support between 1 January 2020, and 30 April 2022. The study compared various physiological parameters between the control and the observation group. These included blood gas analysis, pulmonary artery pressure, ejection fraction, invasive mean arterial pressure, heart rate, cerebral oxygenation, intestinal oxygenation, renal oxygenation, and duration of blood exchange. Furthermore, the study also compared the changes in brain metabolic and salivary cortisol indicators between the two groups of children. Results: The results did not reveal any significant difference in PH, PaO2, and duration of blood exchange between the control and the observation group. However, the observation group's invasive mean arterial pressure, ejection fraction, cerebral oxygenation, intestinal oxygenation, and renal oxygenation were higher than those of the control group. Furthermore, compared with the control group, the pulmonary artery pressure, heart rate, and PaCO2 were lower in the observation group. There was a statistically significant difference between the two groups of children in the relevant clinical indicators (total bilirubin, hemoglobin, SPO2, etc.) after exchange transfusion. After 1â h of blood exchange and after blood exchange, the salivary cortisol levels of the observation group were lower than the control group. The difference was statistically significant. The NAA/Cho and Cho/Cr values of the two groups of children were also significantly different. Conclusion: During blood exchange, unstable hemodynamics substantially impact organ oxygenation. The results of this study suggest that HHFNC and specific ventilation pressure support can improve the respiratory rate and help maintain blood flow stability and organ oxygenation. This technique can also reduce adverse reactions caused by blood exchange, minimizing patient stress and reducing the impact on brain metabolism.
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Anoplophora glabripennis (Asian longhorn beetle, ALB) and Anoplophora chinensis (Citrus longhorn beetle, CLB) are native forest pests in China; they have become important international quarantine pests. They are found using the same Salix aureo-pendula host tree of Cixi, Zhejiang province, China. On this host tree, we collected additional beetles that appeared to be morphologically intermediate between ALB and CLB. By using a stereoscope, we observed that there were several bumps on the base of the elytra, which was inconsistent with ALB, which typically has a smooth elytral base, but was more like CLB, which has numerous short tubercles on the elytral base. Given their sympatry and intermediate morphology, we hypothesized that these may represent ALB × CLB hybrids. We studied the genomic profiles for 46 samples (ALB, CLB, and putative hybrids) using genotyping-by-sequencing (GBS) providing a reduced representation of the entire genome. Employing principal component analyses on the 163 GBS-derived single nucleotide polymorphism data, we found putative hybrids tightly clustered with ALB, but genetically distinct from the CLB individuals. Therefore, our initial hybrid hypothesis was not supported by genomic data. Further, while mating experiments between adult ALB and CLB were successful in 4 separate years (2017, 2018, 2020, and 2021), and oviposition behavior was observed, no progeny was produced. Having employed population genomic analysis and biological hybridization experiments, we conclude that the putative hybrids represent newly discovered morphological variants within ALB. Our approach further confirmed the advantage of genome-wide information for Anoplophora species assignment in certain ambiguous classification cases.
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Escarabajos , Simpatría , Femenino , Animales , Escarabajos/genética , Bosques , ÁrbolesRESUMEN
Exploring and analyzing the effectiveness of an intelligent pacifying strategy information system based on assisted decision-making in reducing the sedation rate of children in short-duration magnetic resonance scans. A total of 125 children aged 3-5 years who underwent MRI scans at a children's hospital from July to December 2021 participated in this study, during which 62 children were assigned to a control group from July to September, and 63 children were assigned to an intervention group from October to December. In the intervention group, the pacifier used the intelligent pacifying strategy information system based on assisted decision-making to assess children's temperament, and utilization of a system-generated pacification plan according to assessment results. In the control group, the pacification plan was formulated by the pacifier based on their own experience and discussion with families of the participating children. The success rate of pacification, duration of pacification, and image quality of the two groups were compare. Compared with the control group, the intervention group had a higher success rate of pacification and lower duration of pacification, with statistically significant differences (P < 0.05). There was no difference in image quality between the two groups (P > 0.05). The intelligent pacifying strategy information system can help reduce the use of the sedative drugs in children aged 3-5 years who underwent a short-duration MRI scan.
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Imagen por Resonancia Magnética , Temperamento , Humanos , Niño , Imagen por Resonancia Magnética/métodos , Factores de Tiempo , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: Renal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA), which is suitable for clinical patients with chronic nephritis. Currently, the chemical constituents of RSGB remains unclear, and its efficacy and mechanism on renal fibrosis have not been reported. METHODS: In our research, ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to describe the chemical profile of RSGB, unilateral ureteral obstruction (UUO) model in mice was established to evaluate the beneficial effect of RSGB on renal fibrosis by biochemical indexes, HE and Masson staining. RNA sequencing and "constituents-targets-pathways" multi-dimensional network was established to mine the mechanisms of RSGB. Key targets were verified by quantitative real-time PCR (qRT-PCR) and western bolt (WB). RESULTS: A total of 201 constituents were identified or tentatively characterized, 15 of which were confirmed with standards. The number of triterpenes was the highest with 49, followed by phenols with 46. RSGB ameliorated the blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, normalizing pathological structure of kidney tissue. RNA sequencing revealed that RSGB regulates 226 differential genes, which were involved in kidney development. According to the "constituents-targets-pathways" network, 26 key active constituents may mainly regulate the inflammatory immune system through 88 corresponding targets. qRT-PCR and WB results showed that RSGB inhibited the activation of the Tgfß1/Smad2/3 pathway, Wnt4/ß-Catenin pathway and NGFR/NF-κB pathway. CONCLUSIONS: Overall, our study, for the first time, characterized 201 chemical constituents in RSGB, and 26 of them were screened out to alleviates renal fibrosis mainly through Tgfß1/Smad2/3 pathway, Wnt4/ß-catenin pathway and NGFR/NF-κB pathway, which may provide a new research strategy for research on the mechanism of traditional Chinese Medicine.
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Although the Se concentration and recovery efficiency of soybean seeds treated with selenate were â¼ 1.8 times those of the selenite treatment, the Se was mainly in the organic form of selenomethionine (>90% of total Se) irrespective of the Se source. The Se concentrations of soybean protein isolate (SPI) and glycinin (11S) were 29.1%-38.6% higher than those of soybean protein concentrate (SPC) and ß-conglycinin (7S) in Se-enriched soybeans, with selenomethionine accounting for > 80% of the Se in all proteins. The content of sulfur-containing methionine in SPI and 11S markedly decreased in Se-enriched soybeans compared with the control. No significant effect of Se was observed on protein content, subunit composition, secondary structure, micromorphology, or functionality. Foliar spray of selenate provides an economical and efficient way to produce Se-enriched soybeans without affecting protein structure and functionality, where SPI and 11S display a high ability to enrich Se (mainly selenomethionine).
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Selenio , Proteínas de Soja , Ácido Selénico , Ácido Selenioso , Selenometionina , Glycine maxRESUMEN
As a crucial food crop, potatoes are highly consumed worldwide, while they are also susceptible to being infected by diverse diseases. Early detection and diagnosis can prevent the epidemic of plant diseases and raise crop yields. To this end, this study proposed a weakly-supervised learning approach for the identification of potato plant diseases. The foundation network was applied with the lightweight MobileNet V2, and to enhance the learning ability for minute lesion features, we modified the existing MobileNet-V2 architecture using the fine-tuning approach conducted by transfer learning. Then, the atrous convolution along with the SPP module was embedded into the pre-trained networks, which was followed by a hybrid attention mechanism containing channel attention and spatial attention submodules to efficiently extract high-dimensional features of plant disease images. The proposed approach outperformed other compared methods and achieved a superior performance gain. It realized an average recall rate of 91.99% for recognizing potato disease types on the publicly accessible dataset. In practical field scenarios, the proposed approach separately attained an average accuracy and specificity of 97.33% and 98.39% on the locally collected image dataset. Experimental results present a competitive performance and demonstrate the validity and feasibility of the proposed approach.
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In China, Wang Bi Granule (WBG)2, composed of 16 herbal and 1 animal-based compounds, is used for clinical treatment of the "Wang Bi" syndrome, commonly referred to as later rheumatoid arthritis (RA) in modern medicine. It is also used in the treatment of ankylosing spondylitis, tuberculous arthritis, and Kashin-Beck disease, which are characterized by joint pain and swelling deformation. However, its pharmacological mechanisms remain unknown. We aimed to characterize the chemical components in WBG and examine the underlying mechanism for RA treatment using integrative pharmacological strategy, including chemical composition detection, efficacy evaluation, and mechanism exploration. We employed UPLC-QTOF-MS/MS to describe the chemical profile of WBG. TNF-α-stimulated RAW264.7 cells were used to simulate the inflammatory processes in RA and evaluate the anti-inflammatory effects of WBG. Network pharmacology was used to determine the mechanism underlying WBG action in RA. A total of 278 chemical components were identified or tentatively characterized. The water extract of WBG improved the imbalance in inflammation in TNF-α-stimulated RAW264.7 cells by regulating 179 differential genes. 55 key active constituents were obtained based on the interactions among "components" targets, RA-related genes, and differential genes (WBG vs TNF-α group) which may ameliorate RA by regulating 161 hub genes primarily involved in inflammation-related pathways. The present study, for the first time, employed integrative pharmacology to characterize the chemical profile of WBG and elucidate its mechanism of action against RA through an inflammation-immune regulatory system.
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Artritis Reumatoide , Medicamentos Herbarios Chinos , Animales , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Ratones , Farmacología en Red , Células RAW 264.7 , Espectrometría de Masas en TándemRESUMEN
Background: Aortic dissection refers to the separation of aortic media and extension along the long axis to form the true and false chambers of the aortic wall. 65-70% of the patients died of cardiac tamponade, arrhythmia, dissection rupture, etc. At present, echocardiography, computed tomography angiography (CTA), etc. are the main diagnosis tools for aortic dissection. To date, there is no rapid serum molecular marker that can be used for differential diagnosis and risk assessment. Objectives: To screen serum molecular markers systematically amid aortic dissection and acute coronary syndrome and to preliminarily identify the pathogenesis of acute aortic dissection. Methods: Related disputes cases of all hospitals were statistically analyzed for the AAD medical disputes ratio, early death ratio and misdiagnosis ratio from the database of Guangdong Province Medical Disputes Coordination Committee from 2013 to 2017. Serum and Aortic tissues samples were respectively quantified by iTRAQ and label-free analysis, further validated by ELISA and protein verified by immunofluorescence and Western blot from AAD and control patients enrolled from the Zhujiang Hospital of Southern Medical University and Guangdong Province people's Hospital from 2016 to 2018. Results: AAD cases ratio accounted for 15.29% in all 150 cardiovascular disputes, 59.26% in all cardiovascular death less than 24 h, and 88.89% in the patients who remained undiagnosed at the time of death, 84 proteins (66 and 18 upregulated and downregulated, respectively) were identified by iTRAQ and 16 proteins (9 and 7 upregulated and downregulated, respectively) by Label-free. Nine proteins (Lumican, FGL1, PI16, MMP9, FBN1, MMP2, VWF, MMRN1, and PF4) related to the pathogenesis of aortic dissection were identified by David /Ease and String techniques as candidate biomarkers for verification test. Four proteins (Lumican, FGL1, PI16, and MMP9) were found to be statistically different after ELISA verification. The expression of FGL1, PI16, and MMP9 proteins was pathologically significantly increased except for Lumican. Histologically, TGF-ß1, α-SMA, and Collagen1 were also significantly higher in the aortic group. Conclusion: Lumican, FGL1, PI16, and MMP9 may be potential biomarkers in AAD patients, and the Lumican-mediated TGF-ß1 pathway is likely to be involved in the pathogenesis of aortic dissection.
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Purpose: DNA methylation heterogeneity is a type of tumor heterogeneity in the tumor microenvironment, but studies on the identification of the molecular heterogeneity of the lung adenocarcinoma genome with respect to DNA methylation sites and their roles in lung cancer progression and prognosis are scarce. Methods: Prognosis-associated DNA methylation subtypes were filtered by the Cox proportional hazards model and then established by unsupervised cluster analysis. Association analysis of these subtypes with clinical features and functional analysis of annotated genes potentially affected by methylation sites were performed. The robustness of the model was further tested by a Bayesian network classifier. Results: Over 7 thousand methylation sites were associated with lung adenocarcinoma prognosis. We identified seven molecular methylation subtypes, including 630 methylation sites. The subtypes yielded the most stable results for differentiating methylation profiles, prognosis, and gene expression patterns. The annotated genes potentially affected by these methylation sites are enriched in biological processes such as morphogenesis and cell adhesion, but their individual impact on the tumor microenvironment and prognosis is multifaceted. Discussion. We revealed that DNA methylation heterogeneity could be clustered and associated with the clinical features and prognosis of lung adenocarcinoma, which could lead to the development of a novel molecular tool for clinical evaluation.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Teorema de Bayes , Biomarcadores de Tumor/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Many negative factors can influence the progressive collapse resistance of reinforced concrete (RC) frame structures. One of the most important factors is the corrosion of rebar within the structure. With increasing severity of corrosion, the duration, robustness, and mechanical performance can be greatly impaired. One specific side effect of rebar corrosion is the significant loss of protection against progressive collapse. In order to quantify the effects of rebar corrosion on load-resisting mechanisms (compressive arch action (CAA) and tensile catenary action (TCA)) of RC frames, a series of numerical investigations were carried out in this paper. The previous experimental results reported in the literature provide a benchmark for progressive collapse behavior as a sound condition and validate the proposed numerical model. Furthermore, based on the verified numerical model, the CAA and TCA with increasing corrosion and an elapsed time from 0 to 70 years are investigated. Comparing with the conventional empirical model, the proposed numerical model has shown the ability and feasibility in predicting the collapse resistance capacity in structures with corroded rebar. Therefore, this numerical modeling strategy provides comprehensive insights into the change of load-resisting mechanisms in these structures, which can be beneficial for optimizing the design.
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Xinglou Chengqi (XLCQ) decoction, composed of three botanical drugs and one inorganic drug, is used in clinics during the treatment of acute stroke complicated with Tanre Fushi (TRFS) syndrome in China. However, its active ingredients and the molecular mechanism have not been clarified. So, we aimed to preliminarily characterize its chemical constituents and investigate its pharmacological mechanisms using an integrative pharmacology strategy, including component analysis, network prediction, and experimental verification. We employed UPLC-QTOF-MS/MS to describe the chemical profile of XLCQ, Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP v2.0, http://www.tcmip.cn/), to assist in identifying the chemical components and predict the putative molecular mechanism against acute stroke complicated with TRFS, and LPS-stimulated BV-2 cells to verify the anti-neuroinflammatory effects of luteolin, apigenin, and chrysoeriol. Altogether, 197 chemical compounds were identified or tentatively characterized in the water extraction of XLCQ, 22 of them were selected as the key active constituents that may improve the pathological state by regulating 27 corresponding targets that are mainly involved in inflammation/immune-related pathways, and furthermore, luteolin, apigenin, and chrysoeriol exhibited good anti-neuroinflammatory effects from both protein and mRNA levels. In summary, it is the first time to employ an integrative pharmacology strategy to delineate 22 constituents that may improve the pathological state of stroke with TRFS by regulating 27 corresponding targets, which may offer a highly efficient way to mine the scientific connotation of traditional Chinese medicine prescriptions. This study might be a supplement for the deficiency of the basic research of XLCQ.
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Wang Bi tablet (WBT) is used to treat rheumatoid arthritis (RA) in China. We employed integrative pharmacology, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to elucidate the active components and mechanism underlying the effect of WBT against RA. The chemical fingerprint of WBT was revealed by UPLC-QTOF-MS/MS, and the chemical composition was identified. The anti-inflammatory effect of WBT was evaluated in TNF-α-stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis, functional enrichment analysis, and network visualization were performed. A total of 293 chemical constituents were preliminarily identified or tentatively characterized in WBT extract, and they effectively inhibited inflammatory response in TNF-α-stimulated RAW264.7 cells. Forty-eight key active constituents were identified based on high-frequency binding to hub targets and their corresponding targets number. Next, 135 corresponding hub genes, which may be the putative targets of WBT in treating RA, were selected. Functionally, the putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to the traditional efficacy of WBT. In summary, this study revealed, for the first time using integrative pharmacology, that WBT may attenuate RA through the inflammation-immune regulation system.