Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-...Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.展开更多
Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue.Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence,influe...Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue.Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence,influencing diverse physiological activities,including immune response,inflammation,and bone metabolism.Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition.However,the impact of these factors on peri-implantitis remains inconclusive.To address this gap,we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis,specifically focusing on DNA methylation and microRNAs(miRNAs or miRs).We searched for relevant literature on PubMed,Web of Science,Scopus,and Google Scholar with keywords including“epigenetics,”“peri-implantitis,”“DNA methylation,”and“microRNA.”DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants.Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis.In addition,we assessed the potential application of DNA methylation and miRNAs in the prevention,diagnosis,and treatment of peri-implantitis,aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition.These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.展开更多
Objective:To evaluate the efficacy and safety of QL1206(a denosumab biosimilar to Xgeva■)in breast cancer patients with bone metastasis(BM)through subgroup analysis of a randomized,double-blind phaseⅢtrial(No.NCT045...Objective:To evaluate the efficacy and safety of QL1206(a denosumab biosimilar to Xgeva■)in breast cancer patients with bone metastasis(BM)through subgroup analysis of a randomized,double-blind phaseⅢtrial(No.NCT04550949).Methods:This subgroup analysis included patients with BM from breast cancer enrolled in a phaseⅢtrial.Patients were randomized(1:1)to receive either three cycles of QL1206 or denosumab(120 mg subcutaneously every 4 weeks).Subsequently,they received 10 cycles of QL1206(120 mg)over 40 weeks,followed by a 20-week safety follow-up.The primary endpoint was the percentage changes from baseline to week 13 in urinary Ntelopeptide corrected for creatinine(u NTx/Cr).Results:The breast cancer cohort consisted of 311 patients.Vertebral involvement(66.4%)was the most prevalent BM site at enrollment,while 27.7%of patients presented with≥3 metastatic bone lesions.At week 13,QL1206 demonstrated a median u NTx/Cr reduction of-69.9%(range:-98.1%-568.0%)vs.-74.3%(range:-97.7%-386.3%)for denosumab.The analysis of covariance revealed comparable least-square means for log-transformed changes:-1.416[95%confidence interval(95%CI):-1.736 to-1.096]vs.-1.501(95%CI:-1.824 to-1.178),yielding an between-group difference of 0.085(90%CI:-0.062-0.232;P=0.343).After a 53-week treatment period,83.6%achieved bone density improvement/disease stabilization.Safety profiles were comparable between groups.Conclusions:QL1206 demonstrated similar efficacy and safety to the reference denosumab in patients with BM from breast cancer,supporting QL1206 as a new option for management of BM from breast cancer.展开更多
<div style="text-align:justify;"> This paper proposes a prediction method based on improved Echo State Network for COVID-19 nonlinear time series, which improves the Echo State Network from the reservo...<div style="text-align:justify;"> This paper proposes a prediction method based on improved Echo State Network for COVID-19 nonlinear time series, which improves the Echo State Network from the reservoir topology and the output weight matrix, and adopt the ABC (Artificial Bee Colony) algorithm based on crossover and crowding strategy to optimize the parameters. Finally, the proposed method is simulated and the results show that it has stronger prediction ability for COVID-19 nonlinear time series. </div>展开更多
A previous study has indicated that Krüppel-like factor 7（KLF7）, a transcription factor that stimulates Schwann cell（SC） proliferation and axonal regeneration after peripheral nerve injury, is a promising the...A previous study has indicated that Krüppel-like factor 7（KLF7）, a transcription factor that stimulates Schwann cell（SC） proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of micro RNA-146 b（mi R-146 b）affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with mi RNA lentivirus, mi RNA inhibitor lentivirus, or KLF7 si RNA lentivirus in vitro. The expression of mi R146 b and KLF7,as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft（ANA） followed by injection of GFP control vector or a lentiviral vector encoding an mi R-146 b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. mi R-146 b directly targeted KLF7 by binding to the 30-UTR, suppressing KLF7. Up-regulation of mi R-146 b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing mi R-146 b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which mi R-146 b was expressed in vivo.Similarly, 4 weeks after the ANA, anti-mi R-146 b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0（anti-peripheral myelin）, and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by mi R-146 b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.展开更多
Removal of noxious dyes is gaining public and technological attention. Herein grafting polymerization was employed to produce a novel adsorbent using acrylic acid and carboxymethyl cellulose for dye removal. Scanning ...Removal of noxious dyes is gaining public and technological attention. Herein grafting polymerization was employed to produce a novel adsorbent using acrylic acid and carboxymethyl cellulose for dye removal. Scanning electron microscopy and Fourier-transform infrared spectroscopy verified the adsorbent formed under optimized reaction conditions. The removal ratio of adsorbent to Methyl Orange, Disperse Blue 2BLN and malachite green chloride reached to 84.2%, 79.6% and 99.9%, respectively. The greater agreement between the calculated and experimental results suggested that pseudo second-order kinetic model better represents the kinetic adsorption data. Equilibrium adsorptions of dyes were better explained by the Temkin isotherm. The results implied that this new cellulose-based absorbent had the universaiity for removal of dyes through the chemical adsorption mechanism.展开更多
BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of death from malignant tumors worldwide. More than 50% of HCC cases occur in China. The prognosis remains poor and overall efficacy is still unsatis...BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of death from malignant tumors worldwide. More than 50% of HCC cases occur in China. The prognosis remains poor and overall efficacy is still unsatisfactory. Chemotherapy resistance is the most important reason for the poor outcome. Much progress has been made in the study of chemotherapy resistance of HCC;however, the specific mechanisms of progression of HCC have still only been partially established.Therefore, the mechanism of chemotherapy resistance in HCC requires more research.AIM To investigate the effect of miR-34 a expression on the growth inhibition of HepG2 cells by doxorubicin.METHODS A recombinant lentiviral vector containing miR-34 a was constructed and transfected into HepG2 cells. The expression of miR-34 a was detected by reverse transcription-polymerase chain reaction(commonly known as RT-PCR) before and after transfection. Cells were exposed to 2 μM doxorubicin or phosphatebuffered saline before and after transfection. Cell viability in each group was detected by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. Changes in expression levels of phospho(p)-p53, sirtuin(SIRT) 1,cyclin D1, cyclin-dependent kinase(CDK) 4, CDK6, BCL-2, multidrug resistance protein(MDR) 1/P glycoprotein(P-gp), and AXL were detected by Western blotting.RESULTS Recombinant lentiviral vector LV-hsa-mir-34 a was successfully constructed by restriction endonuclease digestion and sequencing. RT-PCR showed that expression of miR-34 a in HepG2 cells was significantly upregulated after transfection(P < 0.01). MTT assay showed that growth of HepG2 cells was inhibited after upregulation of miR-34 a, and viability was significantly decreased after combined treatment with doxorubicin(P < 0.01). Flow cytometry showed that the number of HepG2 cells in G1 phase increased, and G1 phase arrest was more obvious after intervention with doxorubicin(P < 0.01). The apoptosis rate of HepG2 cells was increased after upregulation of miR-34 a, and became more obvious after intervention with doxorubicin(P < 0.01). Western blotting showed that upregulation of miR-34 a combined with treatment with doxorubicin caused significant changes in the expression levels of p-p53, SIRT1, cyclin D1, CDK4,CDK6, BCL-2, MDR1/P-gp and AXL proteins(P < 0.01).CONCLUSION MiR-34 a may enhance the inhibitory effect of doxorubicin by downregulating MDR1/P-gp and AXL, which may be related to p53 expression.展开更多
This study proposes a new nonlinear tracking control method with safe angular velocity constraints for a cushion robot. A fuzzy path planning algorithm is investigated and a realtime desired motion path of obstacle av...This study proposes a new nonlinear tracking control method with safe angular velocity constraints for a cushion robot. A fuzzy path planning algorithm is investigated and a realtime desired motion path of obstacle avoidance is obtained. The angular velocity is constrained by the controller, so the planned path guarantees the safety of users. According to Lyapunov theory, the controller is designed to maintain stability in terms of solutions of linear matrix inequalities and the controller's performance with safe angular velocity constraints is derived.The simulation and experiment results confirm the effectiveness of the proposed method and verify that the angular velocity of the cushion robot provided safe motion with obstacle avoidance.展开更多
Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action re...Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.展开更多
Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in ...Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in China.Methods The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China.The direct method was used to get the direct cost of OCD.Indirect costs associated with OCD were estimated using the human capital approach.Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost.Sensitivity analysis was used to analyse the uncertainty of total cost.Results The mean quality of life score for OCD was 52.78(20.46).The annual total cost of OCD per capita was 24503.78(95%CI:22621.53 to 26386.03)renminbi(RMB)(US$3465.88(95%CI:US$3199.65 to US$3732.11)).The annual cost of OCD in China was estimated to be 37.74 billion(95%CI:34.95 billion to 40.53 billion)RMB(equal to US$5.34 billion(95%CI:US$4.94 billion to US$5.73 billion)).Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB(US$3.27 billion)and 370.00 billion RMB(US$52.33 billion).Worse social function status,more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale(Y-BOCS)score were associated with worse quality of life.The numbers of clinic visits and hospitalisations,socioeconomic status,education,Y-BOCS scores and age were found to be significantly associated with total cost.Conclusions OCD is associated with low quality of life and high costs in China.The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis,the provision of evidence-based treatments and relapse prevention strategies.展开更多
The effects of heating rate on the alloy element partitioning and mechanical properties during the phase transformation ofα→βin Ti-6Al-4 V alloy under solution treatment have been investigated by the experiments an...The effects of heating rate on the alloy element partitioning and mechanical properties during the phase transformation ofα→βin Ti-6Al-4 V alloy under solution treatment have been investigated by the experiments and phase field simulations,which reveal the evolutions of microstructure and compositions at the non-equilibrium state and well verify the experimental results.The specific results indicate that the compositions measured through electron probe micro-analysis(EPMA)under a lower heating rate are close to the equilibrium ones corresponding to the solution temperature.Heating up to the target solution temperature,as the heating rate increases,the Al content decreases and V increases in the primaryα(α_(p))grain with a larger size,the volume fraction ofα_(p)increases and the composition gradient betweenα_(p)andβphases gets steeper.The interrelated relationship among the diffusion,compositions,solution temperature and free energy of the system has been discussed in detail.Moreover,increasing the heating rate(~20.0 K/min)may help to improve the mechanical properties of the alloy by mainly adjusting theα_(p)/β;volume fractions,α_(p)particle size and secondaryα(α_(p))size during the process of heating up to the solution temperature.These results may shed some light on the optimization of the knowledge-based heat treatment route.展开更多
Salt stress is a typical abiotic stress in plants that causes slow growth,stunting,and reduced yield and fruit quality.Fertilization is necessary to ensure proper crop growth.However,the effect of fertilization on sal...Salt stress is a typical abiotic stress in plants that causes slow growth,stunting,and reduced yield and fruit quality.Fertilization is necessary to ensure proper crop growth.However,the effect of fertilization on salt tolerance in grapevine is unclear.In this study,we investigated the effect of nitrogen fertilizer(0.01 and 0.1 mol L^(-1)NH_(4)NO_(3))application on the salt(200 mmol L^(-1)NaCl)tolerance of grapevine based on physiological indices,and transcriptomic and metabolomic analyses.The results revealed that 0.01 mol L^(-1)NH_(4)NO_(3) supplementation significantly reduced the accumulation of superoxide anion(O_(2)^(-)·),enhanced the activities of superoxide dismutase(SOD)and peroxidase(POD),and improved the levels of ascorbic acid(AsA)and glutathione(GSH)in grape leaves compared to salt treatment alone.Specifically,joint transcriptome and metabolome analyses showed that the differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)were significantly enriched in the flavonoid biosynthesis pathway(ko00941)and the flavone and flavonol biosynthesis pathway(ko00944).In particular,the relative content of quercetin(C00389)was markedly regulated by salt and nitrogen.Further analysis revealed that exogenous foliar application of quercetin improved the SOD and POD activities,increased the AsA and GSH contents,and reduced the H_(2)O_(2) and O_(2)^(-)·contents.Meanwhile,10 hub DEGs,which had high Pearson correlations(R^(2)>0.9)with quercetin,were repressed by nitrogen.In conclusion,all the results indicated that moderate nitrogen and quercetin application under salt stress enhanced the antioxidant system defense response,thus providing a new perspective for improving salt tolerance in grapes.展开更多
基金supported by the Natural Science Foundation of Hubei Provincial Department of Education(D20232101)Shandong Second Medical University 2024 Affiliated Hospital(Teaching Hospital)Scientific Research Development Fund Project(2024FYQ026)+3 种基金the innovative Research Programme of Xiangyang No.1 People’s Hospital(XYY2023ZY01)Faculty Development Grants of Xiangyang No.1 People’s Hospital Affiliated to Hubei University of Medicine(XYY2023D05)Joint supported by Hubei Provincial Natural Science Foundation and Xiangyang of China(2025AFD091)Traditional Chinese Medicine Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine(ZY2025D019).
文摘Background:Diabetic foot,a severe complication of diabetes,is characterized by chronic refractory wounds.Sanhuang Oil,a topical herbal formula,demonstrates significant therapeutic effects including antibacterial,anti-inflammatory,and immunomodulatory activities.However,its active constituents and mechanisms of action against diabetic foot remain to be elucidated.Methods:In this study,the chemical constituents of Sanhuang Oil were identified using UPLC-QE-Orbitrap-MS.Subsequently,the mechanism by which Sanhuang Oil promotes diabetic foot ulcer healing was predicted by integrating network pharmacology and molecular docking.Additionally,diabetic mouse model was established in ICR mice using a combination of a high-fat diet(HFD)and streptozotocin(STZ)chemical induction.A full-thickness skin defect was created on the dorsum of the mice.Wound healing and the healing rate were observed following Sanhuang Oil intervention.The mechanism underlying Sanhuang Oil’s promotion of diabetic ulcer healing was further investigated using transcriptomics and histopathological examination(H&E staining).Results:A total of 97 active ingredients were identified from Sanhuang Oil.Network pharmacology analysis predicted 543 common targets,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis identified 203 relevant pathways.Molecular docking further confirmed high binding affinity(binding energy≤−5.0 kcal/mol)between specific active components in Sanhuang Oil(e.g.,coptisine,phellodendrine,baicalein)and key targets associated with diabetic foot ulcers(e.g.,EGFR,AKT1,STAT3).In vivo experimental results demonstrated that the wound healing rate was significantly higher in Sanhuang Oil-treated groups compared to the model group(P<0.001).HE staining revealed that the high-dose Sanhuang Oil group exhibited more pronounced epithelial tissue coverage over the wound,reduced inflammatory cell infiltration,and increased collagen deposition and fibroblast proliferation.transcriptomic analysis identified Pdk4,Ttn,Csrp3,Actn2,Myoz2,Tnnc2,Myod1,Myog,Myot,and Myf6 as key regulatory proteins involved in promoting wound healing.Conclusion:Sanhuang Oil promotes wound healing in diabetic ulcer mice,potentially by mitigating inflammation and regulating key targets such as Pdk4 to enhance fibroblast function.These findings provide novel insights into the multi-target,multi-pathway mechanism of Sanhuang Oil for treating diabetic foot ulcers.
基金supported by the Basic Public Welfare Research Project of Zhejiang Province(No.LGF22H140007)the Research and Development Project of Stomatology Hospital Affiliated to Zhejiang University School of Medicine(No.RD2022JCXK01)+1 种基金the National Natural Science Foundation of China(No.82301072)the Postdoctoral Science Foundation of China(Nos.2021TQ0277 and 2022M722741)。
文摘Peri-implant diseases are characterized by the resorption of hard tissue and the inflammation of soft tissue.Epigenetics refers to alterations in the expression of genes that are not encoded in the DNA sequence,influencing diverse physiological activities,including immune response,inflammation,and bone metabolism.Epigenetic modifications can lead to tissue-specific gene expression variations among individuals and may initiate or exacerbate inflammation and disease predisposition.However,the impact of these factors on peri-implantitis remains inconclusive.To address this gap,we conducted a comprehensive review to investigate the associations between epigenetic mechanisms and peri-implantitis,specifically focusing on DNA methylation and microRNAs(miRNAs or miRs).We searched for relevant literature on PubMed,Web of Science,Scopus,and Google Scholar with keywords including“epigenetics,”“peri-implantitis,”“DNA methylation,”and“microRNA.”DNA methylation and miRNAs present a dynamic epigenetic mechanism operating around implants.Epigenetic modifications of genes related to inflammation and osteogenesis provide a new perspective for understanding how local and environmental factors influence the pathogenesis of peri-implantitis.In addition,we assessed the potential application of DNA methylation and miRNAs in the prevention,diagnosis,and treatment of peri-implantitis,aiming to provide a foundation for future studies to explore potential therapeutic targets and develop more effective management strategies for this condition.These findings also have broader implications for understanding the pathogenesis of other inflammation-related oral diseases like periodontitis.
文摘Objective:To evaluate the efficacy and safety of QL1206(a denosumab biosimilar to Xgeva■)in breast cancer patients with bone metastasis(BM)through subgroup analysis of a randomized,double-blind phaseⅢtrial(No.NCT04550949).Methods:This subgroup analysis included patients with BM from breast cancer enrolled in a phaseⅢtrial.Patients were randomized(1:1)to receive either three cycles of QL1206 or denosumab(120 mg subcutaneously every 4 weeks).Subsequently,they received 10 cycles of QL1206(120 mg)over 40 weeks,followed by a 20-week safety follow-up.The primary endpoint was the percentage changes from baseline to week 13 in urinary Ntelopeptide corrected for creatinine(u NTx/Cr).Results:The breast cancer cohort consisted of 311 patients.Vertebral involvement(66.4%)was the most prevalent BM site at enrollment,while 27.7%of patients presented with≥3 metastatic bone lesions.At week 13,QL1206 demonstrated a median u NTx/Cr reduction of-69.9%(range:-98.1%-568.0%)vs.-74.3%(range:-97.7%-386.3%)for denosumab.The analysis of covariance revealed comparable least-square means for log-transformed changes:-1.416[95%confidence interval(95%CI):-1.736 to-1.096]vs.-1.501(95%CI:-1.824 to-1.178),yielding an between-group difference of 0.085(90%CI:-0.062-0.232;P=0.343).After a 53-week treatment period,83.6%achieved bone density improvement/disease stabilization.Safety profiles were comparable between groups.Conclusions:QL1206 demonstrated similar efficacy and safety to the reference denosumab in patients with BM from breast cancer,supporting QL1206 as a new option for management of BM from breast cancer.
文摘<div style="text-align:justify;"> This paper proposes a prediction method based on improved Echo State Network for COVID-19 nonlinear time series, which improves the Echo State Network from the reservoir topology and the output weight matrix, and adopt the ABC (Artificial Bee Colony) algorithm based on crossover and crowding strategy to optimize the parameters. Finally, the proposed method is simulated and the results show that it has stronger prediction ability for COVID-19 nonlinear time series. </div>
基金supported by the National Natural Science Foundation of China (81371362, 81641125, and 81500629)the Scientific Research Foundation of Heilongjiang Province, China (LC2017040)+1 种基金the Science Fund of Heilongjiang Provincial Health and Family Planning Commission, China (2016357 and 2016385)the Basic Research Operating Expenses Program of Heilongjiang Provincial Universities, China (2017- KYYWFMY0661)
文摘A previous study has indicated that Krüppel-like factor 7（KLF7）, a transcription factor that stimulates Schwann cell（SC） proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of micro RNA-146 b（mi R-146 b）affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with mi RNA lentivirus, mi RNA inhibitor lentivirus, or KLF7 si RNA lentivirus in vitro. The expression of mi R146 b and KLF7,as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft（ANA） followed by injection of GFP control vector or a lentiviral vector encoding an mi R-146 b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. mi R-146 b directly targeted KLF7 by binding to the 30-UTR, suppressing KLF7. Up-regulation of mi R-146 b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing mi R-146 b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which mi R-146 b was expressed in vivo.Similarly, 4 weeks after the ANA, anti-mi R-146 b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0（anti-peripheral myelin）, and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by mi R-146 b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.
基金financially supported by the National Natural Science Foundation of China(No.21104047)the Outstanding Young Innovative Fund of Xinjiang Bingtuan,China(No.2010JC25)
文摘Removal of noxious dyes is gaining public and technological attention. Herein grafting polymerization was employed to produce a novel adsorbent using acrylic acid and carboxymethyl cellulose for dye removal. Scanning electron microscopy and Fourier-transform infrared spectroscopy verified the adsorbent formed under optimized reaction conditions. The removal ratio of adsorbent to Methyl Orange, Disperse Blue 2BLN and malachite green chloride reached to 84.2%, 79.6% and 99.9%, respectively. The greater agreement between the calculated and experimental results suggested that pseudo second-order kinetic model better represents the kinetic adsorption data. Equilibrium adsorptions of dyes were better explained by the Temkin isotherm. The results implied that this new cellulose-based absorbent had the universaiity for removal of dyes through the chemical adsorption mechanism.
基金the National Natural Science Foundation of China,No.81302124Shandong Key R and D Program No.2017GSF218038Shandong Provincial Natural Science Foundation,No.ZR2014HP065
文摘BACKGROUND Hepatocellular carcinoma(HCC) is the third leading cause of death from malignant tumors worldwide. More than 50% of HCC cases occur in China. The prognosis remains poor and overall efficacy is still unsatisfactory. Chemotherapy resistance is the most important reason for the poor outcome. Much progress has been made in the study of chemotherapy resistance of HCC;however, the specific mechanisms of progression of HCC have still only been partially established.Therefore, the mechanism of chemotherapy resistance in HCC requires more research.AIM To investigate the effect of miR-34 a expression on the growth inhibition of HepG2 cells by doxorubicin.METHODS A recombinant lentiviral vector containing miR-34 a was constructed and transfected into HepG2 cells. The expression of miR-34 a was detected by reverse transcription-polymerase chain reaction(commonly known as RT-PCR) before and after transfection. Cells were exposed to 2 μM doxorubicin or phosphatebuffered saline before and after transfection. Cell viability in each group was detected by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. Changes in expression levels of phospho(p)-p53, sirtuin(SIRT) 1,cyclin D1, cyclin-dependent kinase(CDK) 4, CDK6, BCL-2, multidrug resistance protein(MDR) 1/P glycoprotein(P-gp), and AXL were detected by Western blotting.RESULTS Recombinant lentiviral vector LV-hsa-mir-34 a was successfully constructed by restriction endonuclease digestion and sequencing. RT-PCR showed that expression of miR-34 a in HepG2 cells was significantly upregulated after transfection(P < 0.01). MTT assay showed that growth of HepG2 cells was inhibited after upregulation of miR-34 a, and viability was significantly decreased after combined treatment with doxorubicin(P < 0.01). Flow cytometry showed that the number of HepG2 cells in G1 phase increased, and G1 phase arrest was more obvious after intervention with doxorubicin(P < 0.01). The apoptosis rate of HepG2 cells was increased after upregulation of miR-34 a, and became more obvious after intervention with doxorubicin(P < 0.01). Western blotting showed that upregulation of miR-34 a combined with treatment with doxorubicin caused significant changes in the expression levels of p-p53, SIRT1, cyclin D1, CDK4,CDK6, BCL-2, MDR1/P-gp and AXL proteins(P < 0.01).CONCLUSION MiR-34 a may enhance the inhibitory effect of doxorubicin by downregulating MDR1/P-gp and AXL, which may be related to p53 expression.
基金supported by the Program for Liaoning Excellent Talents in University of China(LJQ2014013)the Liaoning Natural Science Foundation of China(2015020066)
文摘This study proposes a new nonlinear tracking control method with safe angular velocity constraints for a cushion robot. A fuzzy path planning algorithm is investigated and a realtime desired motion path of obstacle avoidance is obtained. The angular velocity is constrained by the controller, so the planned path guarantees the safety of users. According to Lyapunov theory, the controller is designed to maintain stability in terms of solutions of linear matrix inequalities and the controller's performance with safe angular velocity constraints is derived.The simulation and experiment results confirm the effectiveness of the proposed method and verify that the angular velocity of the cushion robot provided safe motion with obstacle avoidance.
基金supported by the National Natural Science Foundation of China No.81072901the New Teacher Fund for Doctor Station,Ministry of Education,No.20120013110013+1 种基金grants from the Nautical Traditional Chinese Medicine Discipline,No.522/0100604054grants from the Nautical Traditional Chinese Medicine Collaborative Innovation Center,No.522/0100604299
文摘Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.
基金This research was supported by grants from the Shanghai Municipal Health Commission(SMHC)(2019ZB0201)Shanghai Clinical Research Center for Mental Health(19MC1911100)SMHC Clinical Research Center(CRC2018ZD03).
文摘Background Obsessive-compulsive disorder(OCD)is considered a very debilitating disorder with severe loss of quality of life and income.Aims This study estimates the quality of life and economic consequences of OCD in China.Methods The research team interviewed 639 patients with OCD in 13 hospitals in 12 cities in China.The direct method was used to get the direct cost of OCD.Indirect costs associated with OCD were estimated using the human capital approach.Linear regression analysis was conducted for quality of life and generalised linear model analysis was conducted for total cost.Sensitivity analysis was used to analyse the uncertainty of total cost.Results The mean quality of life score for OCD was 52.78(20.46).The annual total cost of OCD per capita was 24503.78(95%CI:22621.53 to 26386.03)renminbi(RMB)(US$3465.88(95%CI:US$3199.65 to US$3732.11)).The annual cost of OCD in China was estimated to be 37.74 billion(95%CI:34.95 billion to 40.53 billion)RMB(equal to US$5.34 billion(95%CI:US$4.94 billion to US$5.73 billion)).Sensitivity analysis showed that the total annual cost of OCD in China was between 23.15 billion RMB(US$3.27 billion)and 370.00 billion RMB(US$52.33 billion).Worse social function status,more psychiatric symptoms and higher Yale Brown Obsessive-Compulsive Scale(Y-BOCS)score were associated with worse quality of life.The numbers of clinic visits and hospitalisations,socioeconomic status,education,Y-BOCS scores and age were found to be significantly associated with total cost.Conclusions OCD is associated with low quality of life and high costs in China.The findings call for concerted efforts to improve services for patients with OCD.Improvements may include early detection and diagnosis,the provision of evidence-based treatments and relapse prevention strategies.
基金support from the National Natural Science Foundation of China(No.51701219)the Doctoral Scientific Research Foundation of Liaoning Province(No.20180540133)the Special Project on Information Technology of the Chinese Academy of Sciences(No.XXH13506–304)。
文摘The effects of heating rate on the alloy element partitioning and mechanical properties during the phase transformation ofα→βin Ti-6Al-4 V alloy under solution treatment have been investigated by the experiments and phase field simulations,which reveal the evolutions of microstructure and compositions at the non-equilibrium state and well verify the experimental results.The specific results indicate that the compositions measured through electron probe micro-analysis(EPMA)under a lower heating rate are close to the equilibrium ones corresponding to the solution temperature.Heating up to the target solution temperature,as the heating rate increases,the Al content decreases and V increases in the primaryα(α_(p))grain with a larger size,the volume fraction ofα_(p)increases and the composition gradient betweenα_(p)andβphases gets steeper.The interrelated relationship among the diffusion,compositions,solution temperature and free energy of the system has been discussed in detail.Moreover,increasing the heating rate(~20.0 K/min)may help to improve the mechanical properties of the alloy by mainly adjusting theα_(p)/β;volume fractions,α_(p)particle size and secondaryα(α_(p))size during the process of heating up to the solution temperature.These results may shed some light on the optimization of the knowledge-based heat treatment route.
基金supported by the Key Talent Project of Gansu Provincial Party Committee Organization Department Funding,China(2023RCXM23)the Industrial Support of Gansu Provincial Department of Education Funding,China(2021CYZC-55)the Key Research and Development Projects of Gansu Provincial Funding,China(21YF5NA090)。
文摘Salt stress is a typical abiotic stress in plants that causes slow growth,stunting,and reduced yield and fruit quality.Fertilization is necessary to ensure proper crop growth.However,the effect of fertilization on salt tolerance in grapevine is unclear.In this study,we investigated the effect of nitrogen fertilizer(0.01 and 0.1 mol L^(-1)NH_(4)NO_(3))application on the salt(200 mmol L^(-1)NaCl)tolerance of grapevine based on physiological indices,and transcriptomic and metabolomic analyses.The results revealed that 0.01 mol L^(-1)NH_(4)NO_(3) supplementation significantly reduced the accumulation of superoxide anion(O_(2)^(-)·),enhanced the activities of superoxide dismutase(SOD)and peroxidase(POD),and improved the levels of ascorbic acid(AsA)and glutathione(GSH)in grape leaves compared to salt treatment alone.Specifically,joint transcriptome and metabolome analyses showed that the differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)were significantly enriched in the flavonoid biosynthesis pathway(ko00941)and the flavone and flavonol biosynthesis pathway(ko00944).In particular,the relative content of quercetin(C00389)was markedly regulated by salt and nitrogen.Further analysis revealed that exogenous foliar application of quercetin improved the SOD and POD activities,increased the AsA and GSH contents,and reduced the H_(2)O_(2) and O_(2)^(-)·contents.Meanwhile,10 hub DEGs,which had high Pearson correlations(R^(2)>0.9)with quercetin,were repressed by nitrogen.In conclusion,all the results indicated that moderate nitrogen and quercetin application under salt stress enhanced the antioxidant system defense response,thus providing a new perspective for improving salt tolerance in grapes.
