ABSTRACT
Background/Aims@#Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. @*Methods@#Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. @*Results@#Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. @*Conclusions@#The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.
ABSTRACT
ObjectiveTo compare and evaluate the clinical efficacy of five classical prescriptions for acute attack of bronchial asthma （BA） and cough variant asthma （CVA） in children， and to further compare and assess the effect of them on cold-induced asthma or heat-induced asthma. MethodRandomized controlled trials （RCT） on the treatment of acute attack of asthma with five classical prescriptions （Sanzi Yangqintang， Maxing Shigantang， Shegan Mahuangtang， Xiao Qinglongtang， and Dingchuantang） were retrieved from China Science and Technology Journal Database （VIP）， China National Knowledge Infrastructure （CNKI）， and Wanfang Data （from establishment to August 15， 2021）. The eligible RCT were evaluated and the data were extracted for network Meta-analysis by Stata 16.0. ResultA total of eligible 47 RCT were screened out， involving 5 114 children with acute attack of asthma and 10 intervention measures. Among them， 16 RCT （1 912 children， 6 intervention measures） were about the cold-induced asthma and 10 RCT （1 054 cases， 4 intervention measures） focused on the heat-induced asthma. According to the Meta-analysis， among the 10 interventions， Maxing Shigantang + routine treatment of western medicine demonstrated the most significant effect， and the effect of the interventions was in the following order： Maxing Shigantang + routine treatment of western medicine > routine treatment of western medicine， Shegan Mahuangtang + routine treatment of western medicine> Xiao Qinglongtang + routine treatment of western medicine > Shegan Mahuangtang > Dingchuantang + routine treatment of western medicine. For the cold-induced asthma， the effect of Shegan Mahuangtang + routine treatment of western medicine was remarkable， and for the heat-induced asthma， the corresponding intervention was Dingchuantang + routine treatment of western medicine. Shegan Mahuangtang was outstanding in improving the percentage of forced expiratory volume in the first second in predicted value （FEV1%）. ConclusionThe combination of western medicine with the five prescriptions was more effective than the western medicine alone， particularly the combination with Maxing Shigantang. The combination of Shegan Mahuangtang and western medicine was outstanding in the treatment of cold-induced asthma， while the corresponding intervention for heat-induced asthma was the combination of Dingchuantang and western medicine. However， a large number of RCT with scientific design and higher quality are still needed to verify the conclusion.
ABSTRACT
ObjectiveTo explore the effect and mechanism of Sangmei Zhike granule （SMZK） on airway inflammation in rats with cough variant asthma（CVA）. MethodSix-week-old male SD rats were randomly divided into normal group， model group， and SMZK （2.48 g·kg-1） group. The rats in the model group and the SMZK group received intraperitoneal injection of a mixed solution containing 10% ovalbumin （OVA） and aluminium hydroxide on the 1st and 8th days and aerosol inhalation of 1% OVA solution from the 15th day for CVA model induction. The intervention lasted for two weeks from the 15th day. At the end of animal manipulation， the lung function was detected and inflammatory cells in the peripheral blood were counted. The serum interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-10 （IL-10） levels were determined. Hematoxylin-eosin （HE） staining was performed on the lungs. Western blot was used to detect the protein expression of nuclear factor kappa-B （NF-κB） and its inhibitor α（IκBα） in lung tissues. ResultCompared with the normal group， the model group showed reduced forced expiratory volume in the first 0.1 second （FEV0.1），FEV0.1/forced vital capacity （FVC），and forced expiratory flow 50% （FEF50%） （P<0.05， P<0.01）， increased white blood cells and eosinophils （P<0.01）， and up-regulated serum IL-4， IL-5， and IL-10 （P<0.01）. As revealed by HE staining， the model group displayed shed epithelial cells of the bronchus， airway stenosis， hyperplasia and expansion of mucous glands， disarrangement of layer structures， disorderly arranged cells， and extensive infiltration of inflammatory cells. The protein expression of NF-κB p65 was higher （P<0.01） and that of IκBα was lower （P<0.01） in the lung tissues of the model group than that in the normal group. Compared with the model group， the SMZK group showed increased FEV0.1，FEV0.1/FVC，and FEF50% （P<0.05）， decreased white blood cells and eosinophils in the peripheral blood （P<0.01）， and declining serum IL-4， IL-5， IL-10 （P<0.01）. HE staining demonstrated mild bronchial mucosal injury and relieved inflammatory cell infiltration， gland hyperplasia， and epithelial degeneration and necrosis in the SMZK group. The protein expression of NF-κB p65 was decreased （P<0.05） and that of IκBα was increased （P<0.05） in lung tissues of the SMZK group than that in the model group. ConclusionSMZK can improve lung function and inhibit airway inflammation in rats with CVA. The underlying mechanism may be related to the regulation of IκBα/NF-κB protein expression in the lungs.
ABSTRACT
ObjectiveTo observe the therapeutic effect and antioxidant mechanism of Xiaochuanning granule on psychological stress-related asthma in rats. MethodThe 6-week-old male SD rats were randomly divided into the normal group， asthma group， stress group， stress-related asthma group， western medicine group （atomization of budesonide suspension） and traditional Chinese medicine （TCM） group （Xiaochuanning granule 2.48 g·kg-1）. The asthma model was established during 28 days by intraperitoneal injection of 10% ovalbumin（OVA）on the 1st and 8th days and inhaling of vapourized 1% OVA started at the 15th day. Stress group， stress-related asthma group， western medicine group and TCM group were given restraint stimulation during the 28 days to establish the psychological stress-related asthma model. Rats in each group were administered with corresponding drug for 14 days from the 15th day. The sucrose preference test and open field test were performed at the 15th and 28th days. At the end of experiment， the body weight， serum interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） levels， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione （GSH） in lung tissues were detected by assay kits. Hematoxylin-eosin（HE） staining was conducted to observe the pathological changes in lung tissues. Meanwhile， Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and hemeoxygenase-1 （HO-1） in lung tissues. ResultCompared with the stress-related asthma group， the body weight， sugar water consumption rate and open field distance in the TCM group were significantly increased （P<0.05）， and the serum IL-4， IL-5， IL-13 levels were significantly decreased （P<0.05）， the levels of SOD and GSH in lung tissues increased significantly （P<0.05）， while the level of MDA decreased significantly （P<0.05）. HE staining showed that the bronchial mucosal injury， inflammatory cell infiltration， gland hyperplasia， epithelial degeneration and necrosis were significantly ameliorated in the TCM group than in the stress-related asthma group. The expression of Nrf2 and HO-1 protein in lung tissues also increased significantly （P<0.05）. ConclusionXiaochuanning Granule can regulate the psychological stress state of stress-related asthmatic rats， alleviate airway inflammatory reaction， and suppress oxidation， which is related to its up-regulation of the Nrf2/HO-1 protein expression.
ABSTRACT
ObjectiveTo explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway. MethodAfter adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （n=8） and an experimental group （n=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg-1） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7th day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （n=8）， a prednisone acetate （1.17 mg·kg-1） group （n=8）， a low-dose BFK （13.59 g·kg-1） group （n=8）， and a high-dose BFK （27.18 g·kg-1） group （n=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared. ResultCompared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn） （P<0.05， P<0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （P<0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （P<0.01）， and up-regulated expression of Wnt3a and β-catenin （P<0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （P<0.05， P<0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （P<0.05， P<0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （P<0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （P<0.05， P<0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （P<0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （P<0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （P<0.05）. The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （P<0.05， P<0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （P<0.01）. ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.
ABSTRACT
ObjectiveTo explore the underlying molecular mechanism of Xiaochuanning granules in the treatment of bronchial asthma based on the network pharmacology and experimental verification through the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway on ovalbumin （OVA） sensitization-induced bronchial asthma model in rats. MethodThe main active ingredients and targets of Xiaochuanning Granules were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to bronchial asthma were obtained from five disease databases such as GeneCards and Online Mendelian Inheritance in Man （OMIM）. The common targets were screened out through the Venn diagram. STRING was used to construct the protein-protein interaction （PPI） network of "compound-disease"， and Cytoscape 3.8.0 was used to establish a network of key active ingredients of Xiaochuanning granules and core target genes （"ingredient-gene" network）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed through DAVID. The bronchial asthma model was induced by OVA stimulation in rats. Bronchial and lung tissue inflammation was observed by hematoxylin-eosin （HE） staining， and the enrichment analysis results of the network pharmacology were verified by Western blot. ResultIn this experiment， 232 active ingredients and 4 687 related targets of Xiaochuanning granules were screened out， and 233 common targets of Xiaochuanning granules and bronchial asthma were collected， including eosinophil-derived neurotoxin 1 （EDN1）， cyclic AMP response element-binding protein 1 （CREB1）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 14 （MAPK14）， and Akt1. KEGG pathway analysis revealed 186 related signaling pathways， indicating that the PI3K/Akt signaling pathway presumedly played a key role in the treatment of bronchial asthma by Xiaochuanning granules. The animal experiment showed that Xiaochuanning granules relieved the airway inflammation and smooth muscle hyperplasia in rats and down-regulated the gene expression of PI3K and Akt as compared with the conditions in the model group （P<0.05）. ConclusionXiaochuanning granules have the characteristics of multi-component， multi-target， and multi-pathway synergistic effect in the treatment of asthma. Xiaochuanning granules may exert anti-inflammatory effects by regulating the expression of genes related to the PI3K/Akt signaling pathway. The present study is expected to provide a theoretical basis for follow-up in-depth research on the complex mechanism of Xiaochuanning granules in the treatment of bronchial asthma.
ABSTRACT
Background/Aims@#Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. @*Methods@#Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). @*Results@#Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. @*Conclusions@#Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.
ABSTRACT
Background@#Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. @*Methods@#We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. @*Results@#In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. @*Conclusion@#ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD.
ABSTRACT
As a traditional Chinese medicine， Ziziphi Spinosae Semen （ZSS） has the functions of tonifying liver， tranquilizing heart， astringent sweat and producing body fluid， which is used to treat neurasthenia， insomnia， dreaminess， debility， night sweat and so on. With the rapid and constant development of ZSS resource industry and its medicinal value， a large number of by-products and waste generated in the production and processing process， resulting in serious environmental problems. In general， the utilization rate of ZSS resources was still not high. Based on this， the chemical components and potential resources of ZSS were systematically combed from the perspective of the medicinal parts and bioactive components in this paper， and the authors had summarized that the widely application of ZSS and its by-products （fruit， leaf， root， etc.） in the fields of food， medicine， functional food and other areas was discovered and summarized as feed， feed additives， activated carbon， organic fertilizer， etc. In addition， this paper systematically summarized the current environmental protection problems of the industry， and put forward suggestions for improvement， aiming at reducing environmental pollution and improving the utilization efficiency of resources， so as to provide reference and basis for the comprehensive utilization of ZSS and its by-products， and promote the green， economical and double-effect development of the industry.
ABSTRACT
Background/Aims@#Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. @*Methods@#CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography–mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. @*Results@#The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. @*Conclusions@#CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability
ABSTRACT
The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC
ABSTRACT
Background/Aims@#Coenzyme Q10 (CoQ10), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ10 (CoQ10-W) and compared its effects with conventional lipid-soluble CoQ10 (CoQ10-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. @*Methods@#CoQ10-W was developed from a glycyrrhizic-carnitine mixed layer CoQ10 micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ10-L or CoQ10-W. CoQ10 level in plasma and kidney were measured using liquid chromatography–mass spectrometry. CoQ10-W and CoQ10-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. @*Results@#The plasma CoQ10 level was significantly higher in the CoQ10-W group than in the CoQ10-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ10-L or CoQ10-W groups compared with that in the Tac group. CoQ10-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ10-L or CoQ10-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ10-L and CoQ10-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. @*Conclusions@#CoQ10-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ10-L, possibly associated with improved CoQ10 bioavailability
ABSTRACT
Background/Aims@#Coenzyme Q10 (CoQ10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ10-based micelle formulation (CoQ10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). @*Methods@#We developed CoQ10-W from a glycyrrhizic-carnitine mixed layer CoQ10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ10 (CoQ10-L) or CoQ10-W for 4 weeks. Their plasma and pancreatic CoQ10 concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ10-W and CoQ10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. @*Results@#The plasma CoQ10 level was significantly increased in the CoQ10-W group compared to that in the CoQ10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ10-W than CoQ10-L. Electron microscopy revealed that CoQ10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ10-L. In vitro studies showed that CoQ10-L and CoQ10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. @*Conclusions@#CoQ10-W has better therapeutic efficacy than CoQ10-L in TAC-induced DM.
ABSTRACT
Objective To establish a human activity recognition （HAR）model based on human activity signals obtained by built-in sensors of the mobile phone, so as to support daily physical state assessment, special population monitoring and other biomedical researches. Methods The mobile signal was collected using the mobile phone built-in sensor, and the public data set UCI HAR and WISDM were used as experimental data. The HAR model was established by using the feature extraction method combined with convolutional neural network and autoregressive model. Results The models all achieved more than 90% recognition accuracy in the self-collected dataset, UCI HAR and WISDM. Conclusions The introduction of autoregressive model can avoid the manual design eigenvalues and effectively reduce the computational complexity of large-scale stacked convolutional layers. The research findings prove that the method based on feature fusion can effectively recognize human activity.
ABSTRACT
Estrogen receptor (ER) and progesterone receptor (PR) are two important members of steroid receptors family, an evolutionarily conserved family of transcription factors. Upon binding to their ligands, ER and PR enter cell nucleus to interact with specific DNA element in the context of chromatin to initiate the transcription of diverse target genes, which largely depends on the timely recruitment of a wide range of cofactors. Moreover, the interactions between steroid hormones and their respective receptors also trigger post-translational modifications on these receptors to fine-tune their transcriptional activities. Besides the well-known phosphorylation modifications on tyrosine and serine/threonine residues, recent studies have identified several other covalent modifications, such as ubiquitylation and sumoylation. These post-translational modifications of steroid receptors affect its stability, subcellular localization, and/or cofactor recruitment; eventually influence the duration and extent of transcriptional activation. This review is to focus on the recent research progress on the transcriptional activation of nuclear ER and PR as well as their physiological functions in early pregnancy, which may help us to better understand related female reproductive diseases.
Subject(s)
Ligands , Phosphorylation , Receptors, Estrogen , Receptors, Progesterone , Sumoylation , Transcriptional ActivationABSTRACT
The seeds of Rabdosia rubescens were as the materials to research the impacts of different lead (Pb2+) concentrations(0, 135, 270, 540, 1 080 mg x L(-1)) on seed germination and seedling growth. The results show that: Low concentration of lead had no obvious effect on early germination of the seed, the germination vigor and germination speed were lightly higher but not significantly differed at the level of Pb concentration 135 mg x L(-1) with control group; Mid-high concentration of Pb solution (270-1 080 mg x L(-1)) significantly inhibited the seed germination and seedling growth, which reduced the seed germination rate, germination vigor, germination index, embryo root length and shoot length, growth index with increasing of Pb concentrations. There was a inhibitory effect on embryo shoot length and root length at mid-high lead concentrations stress, and stronger inhibitory effect on root , which was more sensitive than shoot to Pb stress(P < 0.05). Pb bioaccumulation coefficient (BC) was 0.76-2.59, increased with concentration of Pb; Pb enrichment in seedling mainly caused the growth inhibition. The fitting model predictive analyses show, the critical concentration of Pb, which causes the germination rate and biomass fresh weight reducing 10%, is 195.18, 101.65 mg x L(-1).
Subject(s)
Germination , Isodon , Lead , Toxicity , Seedlings , Seeds , Stress, PhysiologicalABSTRACT
<p><b>OBJECTIVE</b>To observe the clinical effect of the concentrated suture fixation method on skin transplantation on deep burn wound or wound of cicatricial deformity after burn in the jaw and neck region.</p><p><b>METHODS</b>One hundred and fourteen patients, hospitalized from April 2002 to December 2011, with deep burn or cicatricial deformity after burn in the jaw and neck region, were divided into packaging group and concentrated suture group according to the random number table. Each group had 57 patients including 48 cases with deep burn and 9 cases with cicatricial deformity. Traditional suture-package fixation method and concentrated suture fixation method were respectively used in packaging group and concentrated suture group to fix the autologous medium split-thickness skin in transplantation on wounds or scars. On post operation day (POD) 14, the skin microcirculatory perfusion flow of skin graft was measured, and the occurrence of ecchymoma, infection, and necrosis of skin in operative region were observed. The elasticity and contracture of grafted skin and scar hyperplasia on wound edge were observed 6 months after operation. Measurement data were processed with u test, while enumeration data with Fisher's exact test or Chi-square test.</p><p><b>RESULTS</b>(1) On POD 14, the skin microcirculatory perfusion flow in concentrated suture group [(2.86 +/- 0.8) V] was significantly higher than that in packaging group [(2.33 +/- 0.15) V, u = 17.776, P < 0.05]. (2) Ecchymoma occurred in 4 patients of packaging group and 3 patients of concentrated suture group, but the difference between two groups was not statistically significant (chi 2 = 0.152, P > 0.05). (3) Infection in operative region was observed in 1 patient of packaging group, while no patient in concentrated suture group showed this symptom. The difference between two groups was not statistically significant (P > 0.05). (4) Grafted skin in 6 patients of packaging group showed foliated necrosis, which was not observed on those of patients in concentrated suture group. The difference between two groups was statistically significant (P < 0.05). (5) Centipede leg-like scar hyperplasia on wound edge occurred in 21 patients in packaging group and 6 patients in concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 10.920, P < 0.05). (6) Poor elasticity of grafted skin was detected in 17 patients of packaging group and 4 patients of concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 9.865, P < 0.05). (7) Obvious contracture of grafted skin was observed in 15 patients of packaging group and 4 patients of concentrated suture group, and the difference between two groups was statistically significant (chi 2 = 11.684, P < 0.05).</p><p><b>CONCLUSIONS</b>Concentrated suture fixation method is suitable for application in transplantation of big sheet skin on wound in the jaw and neck region. It has high survival rate and is convenient for postoperative observation.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Burns , General Surgery , Cicatrix , General Surgery , Jaw , General Surgery , Neck , General Surgery , Skin Transplantation , Methods , Sutures , Transplantation, Autologous , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the influence of high-voltage electrical burn (HEB) on the aggregation and adhesion of platelet and leukocyte in rats and the interventional effect of pentoxifylline (PTX).</p><p><b>METHODS</b>One hundred and eighty SD rats were divided into control, electrical burn (EB), and pentoxifylline treatment (PT) groups according to the random number table, with 60 rats in each group. (1) Ten rats were taken from each group at 15 minutes before injury for the observation of the microcirculatory perfusion of chest skin with Laser Doppler Perfusion Imager (LDPI), and the number of leukocyte adherent to mesenteric venule with Bradford Variable Projection Microscope (BVPM). Serum was collected from heart blood to determine the contents of platelet activating factor (PAF), thromboxane B2 (TXB2), prostacyclin (PGI2), P-selectin, E-selectin and L-selectin by double-antibody sandwich enzyme-linked immunosorbent assay. The ratio of TXB2 to PGI2 was calculated therefrom. (2) Model of HEB was reproduced in the remaining 50 rats of EB group and that of PT group with voltage regulator and experimental transformer (the electrical current applied to the left forelimb and exited from the right hind limb). The remaining 50 rats of control group were sham injured with the same devices without electric current. Within 2 minutes post injury (PIM), rats in control group and EB group were intraperitoneally injected with 2 mL isotonic saline, while rats in PT group were intraperitoneally injected with 2 mL pentoxifylline (50 mg/mL). At PIM 5 and 1, 2, 4, 8 hour(s) post injury (PIH), 10 rats of every group were randomly chosen at each time point for the observation of the microcirculatory perfusion of chest skin and the number of leukocytes adherent to mesenteric venule through the same method as used above, and the levels of the related factors of aggregation and adhesion of platelets and leukocytes were determined, and then the relative ratio was calculated. Data were processed with the analysis of variance of factorial design and LSD test.</p><p><b>RESULTS</b>The contents of PAF, TXB2, PGI2, P-selectin, E-selectin, L-selectin, and the ratio of TXB2 to PGI2, as well as the number of adhered leukocyte in EB group were higher, while the microcirculatory perfusion value was lower than those of control group, with F values from 854.20 to 8156.52, P values all below 0.01. The microcirculatory perfusion value and PGI2 content of PT group were higher, while the contents or number of other indexes were lower than those of EB group, with F values from 33.18 to 1033.99, P values all below 0.01. Only the data within EB group and PT group were comparable. The contents of PAF, TXB2, PGI2, P-selectin, E-selectin, L-selectin, and the ratio of TXB2 to PGI2, as well as the number of adhered leukocyte in EB group and PT group at each time point were significantly higher than those at 15 minutes before injury, while the microcirculation perfusion value was significantly lower than that at 15 minutes before injury (P values all below 0.001), with the exception of the ratio of TXB2 to PGI2 in PT group and E-selectin in EB group and PT group at PIM 5. The contents of PAF, TXB2, and E-selectin and the ratio of TXB2 to PGI2 in EB group peaked at PIH 4, and they were respectively (9.3 ± 0.9) ng/mL, (14.31 ± 0.65) nmol/mL, (271.2 ± 18.4) ng/mL and 4.62 ± 0.26. The contents of PGI2 and P-selectin, and the number of adhered leukocyte in EB group peaked at PIH 8, and they were respectively (3.98 ± 0.24) nmol/mL, (514 ± 24) ng/mL, and (25.50 ± 4.14) per 100 µm venule. The content of L-selectin peaked at PIH 2 [(876 ± 54) ng/mL]. The microcirculatory perfusion value was lowest at PIM 5 [(1.17 ± 0.10) V].</p><p><b>CONCLUSIONS</b>HEB can increase the contents of PAF, TXB2, PGI2, P-selectin, E-selectin, L-selectin, the ratio of TXB2 to PGI2, and the number of adhered leukocyte, as well as decrease the skin microcirculatory perfusion value. PTX can inhibit the aggregation and adhesion of platelets and leukocytes through increasing the content of PGI2 and decreasing contents of other factors mentioned above, thus alleviating the microcirculatory dysfunction after HEB.</p>
Subject(s)
Animals , Male , Rats , Blood Platelets , Burns, Electric , Blood , Leukocytes , Physiology , Pentoxifylline , Pharmacology , Platelet Aggregation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To prove analgesia and sedative effect of adjuvant anesthesia with magnetic auricular point-sticking on abdominal gynecological operation and its effect on postoperative recovery of body function.</p><p><b>METHODS</b>Ninety-two patients with abdominal gynecological operation were randomly divided into 3 groups. The auricular point-sticking group (APS group, n=31) was pasted and pressed by plasters with magnetic beads at bilateral Shenmen, Pizhixia (subcortex), Zigong (uterus) and Penqiang (pelvic cavity), etc. the night before operation. The placebo group (n=31) was pasted by plasters without magnetic beads. The blank group (n=30) was given no intervention. The mental and gastrointestinal functional changes before and 3 days after the operation were observed.</p><p><b>RESULTS</b>As compared with those in the control group and the blank group, the postoperative score of Self rating Anxiety Scale (SAS) was less (25.5 +/- 0.81 vs. 28.9 +/- 3.19, 28.3 +/- 2.36, both P < 0.01), with lower-dose of Innovar [(2.5 + 1.1) mL vs. (3.4 + 1.8) mL, (3.2 + 1.6) mL, both P < 0.05], earlier exsufflation after the operation [(34.2 + 12.1) h vs. (46.3 + 10.9) h, (43.2 + 14.8) h, both P < 0.01] and higher level serum of beta-endorphin before and after the operation in the APS group (all P < 0.05).</p><p><b>CONCLUSION</b>The magnetic auricular point-sticking has sedative, analgesic and function-regulating effects on the abdominal gynecological operation.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Acupuncture Analgesia , Acupuncture, Ear , Adjuvants, Anesthesia , Pain, Postoperative , Drug Therapy , Therapeutics , Postoperative Period , Recovery of FunctionABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinical feature of patients with atrial septal defects (ASD) and the safety and efficacy of transcatheter closure of ASD in elderly patients.</p><p><b>METHODS</b>Between May 2000 and June 2010, 82 patients aged (64.5 ± 3.8) years underwent attempted transcatheter ASD closure. Right heart catheterization was performed before intervention. Echocardiography was made at 1 day, 1, 3, 6 months after the procedure. The pre- and post-closure clinical feature, pulmonary artery pressure (PAP) and cardiac function were evaluated.</p><p><b>RESULTS</b>In 82 patients, 37 (45.1%) patients were associated with pulmonary arterial hypertension (PAH). The systolic PAP and mean PAP [(44.1 ± 12.4) mm Hg (1 mm Hg = 0.133 kPa) and (25.2 ± 6.8) mm Hg, respectively] were measured by right heart catheterization before the procedure. One patient was unsuitable for closure because of severe PAH. The remaining 81 patients underwent successful ASD closure without major complications. After closuring, systolic PAP decreased from (52.7 ± 10.3) mm Hg to (31.8 ± 6.3) mm Hg (P < 0.05), and mean PAP descended from (30.9 ± 4.7) mm Hg to (21.8 ± 3.4) mm Hg (P < 0.05) in the 36 patients with PAH. The cardiac function improved post procedure. There were 6 new-onset atrial fibrillations during follow up.</p><p><b>CONCLUSIONS</b>ASD in elderly patients are commonly associated with PAH. Transcatheter ASD closure is safe and effective in the majority of elderly patients.</p>