Objective: To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. Methods: A total of 9...Objective: To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. Methods: A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3(+) staining in immunochemistry or amplification of fluorescence in situ hybridization (FISH, ratio ≥2.0). Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox's proportional hazards regression model, and the level of significance was P〈0.05. Results: All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 (80.00%) patients had visceral metastasis, and 43 (47.78%) patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months (range, 2-59 months), and the median OS after metastasis or initially local advanced disease was 22 months (range, 2-1 16 months). Conclusions: Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.展开更多
Objective:Triple-negative breast cancer(TNBC)is a heterogeneous disease with poor prognosis.Circulating tumor cells(CTCs)are a promising predictor for breast cancer prognoses but their reliability regarding progr...Objective:Triple-negative breast cancer(TNBC)is a heterogeneous disease with poor prognosis.Circulating tumor cells(CTCs)are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival(PFS)is controversial.We aim to verify their predictive value in TNBC.Methods:In present prospective cohort study,we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC(taken at inclusion in this study)and analyzed correlations between CTC numbers and outcomes and other clinical parameters.Results:Median PFS was 6.0(range:1.0–25.0)months for the entire cohort,in whom we found no correlations between baseline CTC status and initial tumor stage(P=0.167),tumor grade(P=0.783)or histological type(P=0.084).However,among those getting first-line treatment,baseline CTC status was positively correlated with ratio of peripheral natural killer(NK)cells(P=0.032),presence of lung metastasis(P=0.034)and number of visceral metastatic site(P=0.037).Baseline CTC status was predictive for PFS in first-line TNBC(P=0.033),but not for the cohort as a whole(P=0.118).This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration(P=0.049).Conclusions:Baseline CTC status was predictive of lung metastasis,peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment.We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.展开更多
AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induc...AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function.展开更多
Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism.To further elucidate the impact of MFN2,this study aimed to investig...Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism.To further elucidate the impact of MFN2,this study aimed to investigate its significance on hepatocellular carcinoma(HCC)cell function and its potential role in mediating chemosensitivity.Methods This study investigated the effects of silencing and overexpressing MFN2 on the survival,proliferation,invasion and migration abilities,and sorafenib resistance of MHCC97-L HCC cells.Additional experiments were conducted using XAV939(aβ-catenin inhibitor)and HLY78(aβ-catenin activator)to further validate these findings.Results Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells,enhanced their invasion and migration capacities,increased the IC50 of sorafenib,reduced the percentage of TUNEL-positive cells,and decreased the expression of proapoptotic proteins.Additionally,silencing MFN2 markedly induced the nuclear translocation ofβ-catenin,increasedβ-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin expression.Conversely,overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned above.The results confirmed that silencing MFN2 activated theβ-catenin/epithelial-mesenchymal transition(EMT)pathway and reduced the sensitivity of cells to sorafenib,which could be reversed by XAV939 treatment.Conversely,overexpression of MFN2 inhibited theβ-catenin/EMT pathway and increased the sensitivity of cells to sorafenib,which could be altered by HLY78.Conclusion Low expression of MFN2 in HCC cells promotes the nuclear translocation ofβ-catenin,thereby activating the EMT pathway and mediating resistance to sorafenib.展开更多
Human Wharton's jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, ...Human Wharton's jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, a Wnt/13 catenin pathway antagonist, and LeftyA, a Nodal signaling pathway antagonist to induce differentiation into retinal progenitor cells. Inverted microscopy showed that after induction, the spindleshaped or fibroblastlike Wharton's jelly mesenchymal stem cells changed into bulbous cells with numerous processes. Immunofluorescent cytochemical stain ing and reversetranscription PCR showed positive expression of retinal progenitor cell markers, Pax6 and Rx, as well as weakly downregulated nestin expression. These results demonstrate that Wharton's jelly mesenchymal stem cells are capable of differentiating into retinal progenitor cells in vitro.展开更多
Alveolar bone is the thickened ridge of jaw bone that supports teeth.It is subject to constant occlusal force and pathogens invasion,and is therefore under active bone remodeling and immunomodulation.Alveolar bone hol...Alveolar bone is the thickened ridge of jaw bone that supports teeth.It is subject to constant occlusal force and pathogens invasion,and is therefore under active bone remodeling and immunomodulation.Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern.However,a systematic explanation of alveolar bone at single-cell level is still lacking.Here,we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing(scRNA-seq).A more active immune microenvironment is identified in alveolar bone,with a higher proportion of mature immune cells than in long bone.Among all immune cell populations,the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells(MSCs)subpopulation.Alveolar bone monocytes/macrophages express a higher level of Oncostatin M(Osm)compared to long bone,which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs.In summary,our study reveals a unique immune microenvironment of alveolar bone,which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.展开更多
Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-E...Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-Esc and D-Ex)trial in patients with advanced solid cancer.Methods:This was a 3+3 phaseⅠD-Esc trial with a 3-level D-Ex at 5 hospitals in China.Eligible patients for DEsc had advanced solid tumors refractory to standard therapies,and D-Ex enrolled patients with ovarian cancer(OC).Fluzoparib was administered orally once or twice daily(bid)at 11 dose levels from 10 to 400 mg/d.Endpoints included dose-finding,safety,pharmacokinetics,and antitumor activity.Results:Seventy-nine patients were enrolled from March,2015 to January,2018[OC(47,59.5%);breast cancer(BC)(16,20.3%);colorectal cancer(8,10.1%),other tumors(8,10.1%)];48 patients were treated in the D-Esc arm and 31 in the D-Ex arm.The maximum tolerated dose(MTD)was 150 mg bid,with a half-life of 9.14 h.Grade 3/4 adverse events included anemia(7.6%)and neutropenia(5.1%).The objective response rate(ORR)was 30%(3/10)in patients with platinum-sensitive OC and 7.7%(1/13)in patients with BC.Among patients treated with fluzoparib≥120 mg/d,median progression-free survival(m PFS)was 7.2[95%confidence interval(95%CI),1.8-9.3]months in OC,9.3(95%CI,7.2-9.3)months in platinum-sensitive OC,and 3.5(range,2.0-28.0)months in BC.In patients with germline BC susceptibility gene mutation(g BRCAMut)(11/43 OC;2/16 BC),m PFS was 8.9 months for OC(range,1.0-23.2;95%CI,1.0-16.8)and 14 and 28 months for BC(those two patients both also had somatic BRCAMut).Conclusions:The MTD of fluzoparib was 150 mg bid in advanced solid malignancies.Fluzoparib demonstrated single-agent antitumor activity in BC and OC,particularly in BRCAMut and platinum-sensitive OC.展开更多
The interfacial perimeter of gold nanocatalysts is popularly viewed as the active sites for a number of chemical reactions,while the geometrical structure of the interface at atomic scale is less known.Here,TiO2-nanos...The interfacial perimeter of gold nanocatalysts is popularly viewed as the active sites for a number of chemical reactions,while the geometrical structure of the interface at atomic scale is less known.Here,TiO2-nanosheets and nanospindles were adapted to accommodate Au particles(~2.2 nm),forming Au-TiO2{001}and Au-TiO2{101}interfaces.Upon calcination at 623 K in air,HAADF-STEM images evidenced that the Au particles on TiO2{101}enlarged to 3.1 nm and these on TiO2{001}remained unchanged,suggesting the stronger metal-support interaction on TiO2{001}.Au/TiO2{001}was more active for CO oxidation than Au/TiO2{101}system.展开更多
Understanding the hydrological processes of forest ecosystems in Tibetan Plateau is crucial for protecting water resources and the environment, especially considering that evapotranspiration is the most dominant hydro...Understanding the hydrological processes of forest ecosystems in Tibetan Plateau is crucial for protecting water resources and the environment, especially considering that evapotranspiration is the most dominant hydrologic process in most forest systems. SHAW, as a physically based, hydrological model, provides a useful tool for understanding and analyzing evapotranspiration processes. Using the measured data of a faber fir forest ecosystem in eastern Tibetan Plateau, this paper assessed the model performance in simulating evapotranspiration and variability and transferability of the model parameters. Comparison of the simulated results by SHAW to the measured data showed that SHAW performed satisfactorily. Based on analyzing the simulated results by the calibrated and validated SHAW, some ET characteristics of faber fir forest ecosys-tem in the eastern Tibetan Plateau were found: 1) Daily plant transpiration is low, and daily ET mainly comes from surface evaporation including canopy, litter and soil evaporation. Peak ET rate was approxi-mately 4mm/day, occurring around late July. 2) Solar radiation is the most important factor accounting for daily ET variation, while air temperature is the secondary, wind speed and air relative humidity are minor and soil water storage is the least important among all the related factors. 3) The ratio of annual ET to pre-cipitation for the faber fir forest ecosystem in eastern Tibetan Plateau is low (18%) compared with the other forest ecosystems owing to high-elevation, high atmospheric humidity and low annual temperature.展开更多
Carbon sulfide cation(CS^+) plays a dominant role in some astrophysical atmosphere environments. In this work, the rovibrational transition lines are computed for the lowest three electronic states, in which the inter...Carbon sulfide cation(CS^+) plays a dominant role in some astrophysical atmosphere environments. In this work, the rovibrational transition lines are computed for the lowest three electronic states, in which the internally contracted multireference configuration interaction approach(MRCI) with Davison size-extensivity correction(+Q) is employed to calculate the potential curves and dipole moments, and then the vibrational energies and spectroscopic constants are extracted. The Frank–Condon factors are calculated for the bands of X^2^+Σ^+–A^2Π and X^2Σ^+–B^2Σ^+systems, and the band of X^2Σ^+–A^2Π is in good agreement with the available experimental results. Transition dipole moments and the radiative lifetimes of the low-lying three states are evaluated. The opacities of the CS^+ molecule are computed at different temperatures under the pressure of 100 atms. It is found that as temperature increases, the band systems associated with different transitions for the three states become dim because of the increased population on the vibrational states and excited electronic states at high temperature.展开更多
The article published in Vol.4 No.2 102-107, 2013 has been withdrawn by the authors for further revision. This paper will be re-submitted to IJCM after the authors revise it.
The purpose of this study was to analyze the clinical experience of Zan Qiang,a famous doctor of Traditional Chinese Medicine in Shaanxi province,in the treatment of perimenopausal osteoporosis.Zan believed that the m...The purpose of this study was to analyze the clinical experience of Zan Qiang,a famous doctor of Traditional Chinese Medicine in Shaanxi province,in the treatment of perimenopausal osteoporosis.Zan believed that the main etiology and pathogenesis of perimenopausal osteoporosis were "deficiency of kidney essence,decreased marrow and bone",deficiency of liver and kidney"and"stasis caused by deficiency".Although it is a chronic physiological disease,and the pathological process is irreversible,the treatment groups of"tonifying kidney and filling essence","tonifying liver and tonifying kidney"and "tonifying deficiency and promoting blood circulation" can significantly improve the symptoms of patients,slow down the progress of the disease and improve the quality of life of patients.展开更多
The interlayer hybridization(IH)of van der Waals(vdW)materials is thought to be mostly associated with the unignorable interlayer overlaps of wavefunctions(t)in real space.Here,we develop a more fundamental understand...The interlayer hybridization(IH)of van der Waals(vdW)materials is thought to be mostly associated with the unignorable interlayer overlaps of wavefunctions(t)in real space.Here,we develop a more fundamental understanding of IH by introducing a new physical quantity,the IH admixture ratioα.Consequently,an exotic strategy of IH engineering in energy space can be proposed,i.e.,instead of changing t as commonly used,αcan be effectively tuned in energy space by changing the on-site energy difference(2Δ)between neighboring-layer states.In practice,this is feasible via reshaping the electrostatic potential of the surface by deposing a dipolar overlayer,e.g.,crystalline ice.Our first-principles calculations unveil that IH engineering via adjusting 2Δcan greatly tune interlayer optical transitions in transition-metal dichalcogenide bilayers,switch different types of Dirac surface states in Bi_(2)Se_(3)thin films,and control magnetic phase transition of charge density waves in 1H/1T-TaS_(2)bilayers,opening new opportunities to govern the fundamental optoelectronic,topological,and magnetic properties of vdW systems beyond the traditional interlayer distance or twisting engineering.展开更多
Co-electrolysis of waste plastics and carbon dioxide(CO_(2)) into value-added chemicals or fuels is a promising pathway for a sustainable society, but efficient and selective conversion remains a challenge. Herein, a ...Co-electrolysis of waste plastics and carbon dioxide(CO_(2)) into value-added chemicals or fuels is a promising pathway for a sustainable society, but efficient and selective conversion remains a challenge. Herein, a gold-mediated nickel hydroxide(Au/Ni(OH)_(2)) is developed to oxidize waste plastic-derived ethylene glycol(EG) into formate. In-situ electrochemical experiments and theoretical results reveal that the introduction of Au favors the redox properties and EG adsorption behavior of Ni(OH)_(2). The Au/Ni(OH)_(2) catalyst shows an excellent formate selectivity of >90% at high current densities of above 100 m A cm^(-2). When coupled with sputtered bismuth(Bi) cathode for CO_(2) reduction, a high formate Faradic efficiency(FE) of 188.2% at 200 m A cm^(-2)and a good formate productivity of 7.33 mmol m^(-2)s^(-1)at 10 A are obtained in a flow cell and a zero-gap membrane electrode assembly(MEA) cell, respectively. This work demonstrates a promising strategy to convert waste plastics and CO_(2) into valuable products.展开更多
Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel ...Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.展开更多
After converting cropland to forest, carbon Is sequestered in the aggradlng blomass of the new forests, but the question remains, to what extent will the former arable soil contribute as a sink for CO2? Quantifying c...After converting cropland to forest, carbon Is sequestered in the aggradlng blomass of the new forests, but the question remains, to what extent will the former arable soil contribute as a sink for CO2? Quantifying changes In soil carbon Is an Important consideration In the large-scale conversion of cropland to forest. Extensive field studies were undertaken to Identify a number of suitable sites for comparison of soil properties under pasture and forest. The present paper describes results from a study of the effects of first rotation larch on soil carbon In seven stands In an afforestation chronosequence compared with adjacent Korean pine, pasture, and cropland. An adjacent 250-year-old natural forest was Included to give Information on the possible long-term changes In soil carbon In northeast China In 2004. Soil carbon Initially decreased during the first 12 yr before a gradual recovery and accumulation of soil carbon occurred. The Initial (0-12 yr) decrease In soil carbon was an average 1.2% per year among case studies, whereas the Increase In soil carbon (12-33 yr) was 1.90% per year. Together with the carbon sequestration of forest floors, this led to total soil carbon stores of approximately 101.83 Mg/hm^2 over the 33-year chronosequence. Within the relatively short time span, carbon sequestration occurred mainly In tree blomees, whereas soil carbon stores were clearly higher In the 250-year-old plantation (184 Mg/hm^2). The ongoing redistribution of mineral soil carbon In the young stands and the higher soil carbon contents In the 250-year-old afforested stand suggest that nutrient-rich afforestation soils may become greater sinks for carbon (C) In the long term.展开更多
Tumor-associated macrophages(TAMs)facilitate cancer progression by promoting tumor invasion,angiogenesis,metastasis,inflammatory responses,and immunosuppression.Folate receptorβ(FRβ)is overexpressed in TAMs.However,...Tumor-associated macrophages(TAMs)facilitate cancer progression by promoting tumor invasion,angiogenesis,metastasis,inflammatory responses,and immunosuppression.Folate receptorβ(FRβ)is overexpressed in TAMs.However,the clinical significance of FRβ-positive macrophages in lung cancer remains poorly understood.In this study,we verified that FRβoverexpression in lung cancer TAMs was associated with poor prognosis.We utilized a folate-modified lipoplex comprising a folatemodified liposome(F-PLP)delivering a BIM-S plasmid to target both lung cancer cells and FRβ-positive macrophages in the tumor microenvironment.Transfection of LL/2 cells and MH-S cells with F-PLP/pBIM induced cell apoptosis.Injection of F-PLP/pBIM into LL/2 and A549 lung cancer models significantly depleted FRβ-positive macrophages and reduced tumor growth.Treatment of tumor-bearing mice with F-PLP/pBIM significantly inhibited tumor growth in vivo by inducing tumor cell and macrophage apoptosis,reducing tumor proliferation,and inhibiting tumor angiogenesis.In addition,a preliminary safety evaluation demonstrated a good safety profile of F-PLP/pBIM as a gene therapy administered intravenously.This work describes a novel application of lipoplexes in lung cancer targeted therapy that influences the tumor microenvironment by targeting TAMs.展开更多
Rotationally symmetric workpieces of Ti_(2)AlNb-based alloys have great potential for high-temperature service condition in aviation industry,while the poor workability limits their application until now.In this study...Rotationally symmetric workpieces of Ti_(2)AlNb-based alloys have great potential for high-temperature service condition in aviation industry,while the poor workability limits their application until now.In this study,shear spinning and heat treatment were first conducted to investigate the corresponding microstructure evolution and mechanical properties of Ti_(2)AlNb conical workpieces.The microstructure of the 1^(st) and 2^(nd) pass spun workpieces(SP1 and SP2)mainly consisted of B2+retainedα2phases.After two passes spinning,the B2 phase texture changed from<111>//ND of as-received alloy to be<001>//ND.The ultimate tensile stress(UTS)of SP1 and SP2 was increased to 1163 MPa and 932 MPa,respectively,compared with 782 MPa of as-received alloy at 650℃.Also,the yield stress anomaly(YSA)occurred in SP1 and SP2 because{110}<111>and{112}<111>cross slip systems of B2 phase were difficult to slip at or below room temperature(RT),but they became active at 650℃ and above.As an essential step for increasing the spinnability of multi-pass spinning process of the Ti_(2)AlNb alloy,the H3heat treatment scheme,i.e.960℃/2 h+850℃/12 h,was carried out between two successive passes to increase the hot workability,by which the ductility of the heat treated as-spun workpieces with the microstructure of B2+primary O+acicular secondary O+high amount spheroidizedα2phases reached 72.1%at 900℃.After being subject to the H1 heat treatment scheme,i.e.960℃-2 h,the spun workpieces with the microstructure of B2+primary O+intergranular primaryα2phases achieved an optimized comprehensive mechanical properties both at room temperature and 650℃,which should be chosen as the post-spinning heat treatment process for the service requirement.展开更多
Objective: To observe the effects of fuzhengbutu(strengthening antipathogenic qi and tonifying the earth)acupuncture-moxibustion therapy on walking function in the patients with post-stroke hemiplegia.Methods: A total...Objective: To observe the effects of fuzhengbutu(strengthening antipathogenic qi and tonifying the earth)acupuncture-moxibustion therapy on walking function in the patients with post-stroke hemiplegia.Methods: A total of 57 patients with hemiplegia after ischemic stroke treated in our hospital from January2018 through to October 2018 were collected as the study objects. According to random number table,they were divided into a treatment group(29 cases) and a control group(28 cases). In the treatment group, the fuzhengbutu acupuncture-moxibustion therapy combined with rehabilitation treatment was adopted. In the control group, the rehabilitation treatment was given. The persistent walking time and pause time in PIERENSTEP gait measurable training and test system as well as the score of Berg balance scale(BBS) were compared between the two groups.Results: In the treatment group, the persistent walking time after treatment 1.47 ±0.28) s was shorter obviously versus before treatment(2.12 ± 0.38)s, indicating the significant difference(P<0.05). The pause time after treatment was not different obviously versus before treatment(P> 0.05). In the control group,the persistent walking time after treatment(1.88 ± 0.22) s was shorter obviously versus before treatment(2.18 ± 0.30)s, indicating the significant difference(P<0.05). The pause time after treatment was not different obviously versus before treatment(P> 0.05). Before treatment, the differences were not significant in the persistent walking time and pause duration in the patients of either group(P>0.05). After treatment, the persistent walking time in the treatment group was shorter obviously than the control group(P<0.05) and the difference in pause time was not significant between the two groups(P>0.05). Before treatment, there was no difference in BBS score between the two groups(P>0.05). In the treatment group, BBS score(42.79 ±2.78) after treatment was higher than(35.86 ±2.64) before treatment, indicating the significant difference(P<0.05). In the control group, BBS score(39.07 ±2.67) after treatment was higher than(35.86 ±2.64) before treatment, indicating the significant difference(P<0.05). In comparison of BBS score after treatment between the two groups, the score in the treatment group was higher than the control group, indicating the significant difference(P<0.05).Conclusion: Based on rehabilitation treatment, Fuzhengbutu acupuncture-moxibustion therapy effectively improves the walking function of the patients with hemiplegia after ischemic stroke.展开更多
文摘Objective: To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. Methods: A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3(+) staining in immunochemistry or amplification of fluorescence in situ hybridization (FISH, ratio ≥2.0). Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox's proportional hazards regression model, and the level of significance was P〈0.05. Results: All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 (80.00%) patients had visceral metastasis, and 43 (47.78%) patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months (range, 2-59 months), and the median OS after metastasis or initially local advanced disease was 22 months (range, 2-1 16 months). Conclusions: Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.
基金supported by National Natural Science Foundation of China (No.81502269 and No.21273051)a grant from the Chinese Academy of Sciences (No.XDA09030306)
文摘Objective:Triple-negative breast cancer(TNBC)is a heterogeneous disease with poor prognosis.Circulating tumor cells(CTCs)are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival(PFS)is controversial.We aim to verify their predictive value in TNBC.Methods:In present prospective cohort study,we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC(taken at inclusion in this study)and analyzed correlations between CTC numbers and outcomes and other clinical parameters.Results:Median PFS was 6.0(range:1.0–25.0)months for the entire cohort,in whom we found no correlations between baseline CTC status and initial tumor stage(P=0.167),tumor grade(P=0.783)or histological type(P=0.084).However,among those getting first-line treatment,baseline CTC status was positively correlated with ratio of peripheral natural killer(NK)cells(P=0.032),presence of lung metastasis(P=0.034)and number of visceral metastatic site(P=0.037).Baseline CTC status was predictive for PFS in first-line TNBC(P=0.033),but not for the cohort as a whole(P=0.118).This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration(P=0.049).Conclusions:Baseline CTC status was predictive of lung metastasis,peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment.We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.
基金Supported by the Xingtai Key Research and Development Projects (No.2022zz073)the Hebei Key Research and Development Projects (No.23377712D).
文摘AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function.
基金supported by Startup Fund for Scientific Research,Fujian Medical University(No.2019QH1146)Guiyang Science and The Natural Science Foundation of Fujian Province(general program)(No.2020J011061).
文摘Objective Mitofusin-2(MFN2)is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism.To further elucidate the impact of MFN2,this study aimed to investigate its significance on hepatocellular carcinoma(HCC)cell function and its potential role in mediating chemosensitivity.Methods This study investigated the effects of silencing and overexpressing MFN2 on the survival,proliferation,invasion and migration abilities,and sorafenib resistance of MHCC97-L HCC cells.Additional experiments were conducted using XAV939(aβ-catenin inhibitor)and HLY78(aβ-catenin activator)to further validate these findings.Results Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells,enhanced their invasion and migration capacities,increased the IC50 of sorafenib,reduced the percentage of TUNEL-positive cells,and decreased the expression of proapoptotic proteins.Additionally,silencing MFN2 markedly induced the nuclear translocation ofβ-catenin,increasedβ-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin expression.Conversely,overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned above.The results confirmed that silencing MFN2 activated theβ-catenin/epithelial-mesenchymal transition(EMT)pathway and reduced the sensitivity of cells to sorafenib,which could be reversed by XAV939 treatment.Conversely,overexpression of MFN2 inhibited theβ-catenin/EMT pathway and increased the sensitivity of cells to sorafenib,which could be altered by HLY78.Conclusion Low expression of MFN2 in HCC cells promotes the nuclear translocation ofβ-catenin,thereby activating the EMT pathway and mediating resistance to sorafenib.
基金supported by 2010 Com-advanced School Young Diaph Support Project of Heilongjiang Province,China, No. 1155G60
文摘Human Wharton's jelly mesenchymal stem cells were isolated from fetal umbilical cord. Cells were cultured in serumfree neural stem cellconditioned medium or neural stem cellconditioned medium supplemented with Dkk1, a Wnt/13 catenin pathway antagonist, and LeftyA, a Nodal signaling pathway antagonist to induce differentiation into retinal progenitor cells. Inverted microscopy showed that after induction, the spindleshaped or fibroblastlike Wharton's jelly mesenchymal stem cells changed into bulbous cells with numerous processes. Immunofluorescent cytochemical stain ing and reversetranscription PCR showed positive expression of retinal progenitor cell markers, Pax6 and Rx, as well as weakly downregulated nestin expression. These results demonstrate that Wharton's jelly mesenchymal stem cells are capable of differentiating into retinal progenitor cells in vitro.
基金the National Natural Science Foundation of China(NSFC 81722014,81970913)State Key Laboratory of Oral Diseases(SKLOD202008)West China Hospital of Stomatology(RD-03-202010).
文摘Alveolar bone is the thickened ridge of jaw bone that supports teeth.It is subject to constant occlusal force and pathogens invasion,and is therefore under active bone remodeling and immunomodulation.Alveolar bone holds a distinct niche from long bone considering their different developmental origin and postnatal remodeling pattern.However,a systematic explanation of alveolar bone at single-cell level is still lacking.Here,we construct a single-cell atlas of mouse mandibular alveolar bone through single-cell RNA sequencing(scRNA-seq).A more active immune microenvironment is identified in alveolar bone,with a higher proportion of mature immune cells than in long bone.Among all immune cell populations,the monocyte/macrophage subpopulation most actively interacts with mesenchymal stem cells(MSCs)subpopulation.Alveolar bone monocytes/macrophages express a higher level of Oncostatin M(Osm)compared to long bone,which promotes osteogenic differentiation and inhibits adipogenic differentiation of MSCs.In summary,our study reveals a unique immune microenvironment of alveolar bone,which may provide a more precise immune-modulatory target for therapeutic treatment of oral diseases.
文摘Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-Esc and D-Ex)trial in patients with advanced solid cancer.Methods:This was a 3+3 phaseⅠD-Esc trial with a 3-level D-Ex at 5 hospitals in China.Eligible patients for DEsc had advanced solid tumors refractory to standard therapies,and D-Ex enrolled patients with ovarian cancer(OC).Fluzoparib was administered orally once or twice daily(bid)at 11 dose levels from 10 to 400 mg/d.Endpoints included dose-finding,safety,pharmacokinetics,and antitumor activity.Results:Seventy-nine patients were enrolled from March,2015 to January,2018[OC(47,59.5%);breast cancer(BC)(16,20.3%);colorectal cancer(8,10.1%),other tumors(8,10.1%)];48 patients were treated in the D-Esc arm and 31 in the D-Ex arm.The maximum tolerated dose(MTD)was 150 mg bid,with a half-life of 9.14 h.Grade 3/4 adverse events included anemia(7.6%)and neutropenia(5.1%).The objective response rate(ORR)was 30%(3/10)in patients with platinum-sensitive OC and 7.7%(1/13)in patients with BC.Among patients treated with fluzoparib≥120 mg/d,median progression-free survival(m PFS)was 7.2[95%confidence interval(95%CI),1.8-9.3]months in OC,9.3(95%CI,7.2-9.3)months in platinum-sensitive OC,and 3.5(range,2.0-28.0)months in BC.In patients with germline BC susceptibility gene mutation(g BRCAMut)(11/43 OC;2/16 BC),m PFS was 8.9 months for OC(range,1.0-23.2;95%CI,1.0-16.8)and 14 and 28 months for BC(those two patients both also had somatic BRCAMut).Conclusions:The MTD of fluzoparib was 150 mg bid in advanced solid malignancies.Fluzoparib demonstrated single-agent antitumor activity in BC and OC,particularly in BRCAMut and platinum-sensitive OC.
基金supported by Liaoning Revitalization Talents Program (XLYC1807121)National Natural Science Foundation of China (20673054)~~
文摘The interfacial perimeter of gold nanocatalysts is popularly viewed as the active sites for a number of chemical reactions,while the geometrical structure of the interface at atomic scale is less known.Here,TiO2-nanosheets and nanospindles were adapted to accommodate Au particles(~2.2 nm),forming Au-TiO2{001}and Au-TiO2{101}interfaces.Upon calcination at 623 K in air,HAADF-STEM images evidenced that the Au particles on TiO2{101}enlarged to 3.1 nm and these on TiO2{001}remained unchanged,suggesting the stronger metal-support interaction on TiO2{001}.Au/TiO2{001}was more active for CO oxidation than Au/TiO2{101}system.
文摘Understanding the hydrological processes of forest ecosystems in Tibetan Plateau is crucial for protecting water resources and the environment, especially considering that evapotranspiration is the most dominant hydrologic process in most forest systems. SHAW, as a physically based, hydrological model, provides a useful tool for understanding and analyzing evapotranspiration processes. Using the measured data of a faber fir forest ecosystem in eastern Tibetan Plateau, this paper assessed the model performance in simulating evapotranspiration and variability and transferability of the model parameters. Comparison of the simulated results by SHAW to the measured data showed that SHAW performed satisfactorily. Based on analyzing the simulated results by the calibrated and validated SHAW, some ET characteristics of faber fir forest ecosys-tem in the eastern Tibetan Plateau were found: 1) Daily plant transpiration is low, and daily ET mainly comes from surface evaporation including canopy, litter and soil evaporation. Peak ET rate was approxi-mately 4mm/day, occurring around late July. 2) Solar radiation is the most important factor accounting for daily ET variation, while air temperature is the secondary, wind speed and air relative humidity are minor and soil water storage is the least important among all the related factors. 3) The ratio of annual ET to pre-cipitation for the faber fir forest ecosystem in eastern Tibetan Plateau is low (18%) compared with the other forest ecosystems owing to high-elevation, high atmospheric humidity and low annual temperature.
基金Project supported by the National Key Research and Development Program of China(Grant Nos.2017YFA0402300 and 2017YFA0403200)the National Natural Science Foundation of China(Grant Nos.11474032,11534011,U15302611,and 1404180)China Postdoctoral Science Foundation(Grant No.2018M631404)
文摘Carbon sulfide cation(CS^+) plays a dominant role in some astrophysical atmosphere environments. In this work, the rovibrational transition lines are computed for the lowest three electronic states, in which the internally contracted multireference configuration interaction approach(MRCI) with Davison size-extensivity correction(+Q) is employed to calculate the potential curves and dipole moments, and then the vibrational energies and spectroscopic constants are extracted. The Frank–Condon factors are calculated for the bands of X^2^+Σ^+–A^2Π and X^2Σ^+–B^2Σ^+systems, and the band of X^2Σ^+–A^2Π is in good agreement with the available experimental results. Transition dipole moments and the radiative lifetimes of the low-lying three states are evaluated. The opacities of the CS^+ molecule are computed at different temperatures under the pressure of 100 atms. It is found that as temperature increases, the band systems associated with different transitions for the three states become dim because of the increased population on the vibrational states and excited electronic states at high temperature.
文摘The article published in Vol.4 No.2 102-107, 2013 has been withdrawn by the authors for further revision. This paper will be re-submitted to IJCM after the authors revise it.
文摘The purpose of this study was to analyze the clinical experience of Zan Qiang,a famous doctor of Traditional Chinese Medicine in Shaanxi province,in the treatment of perimenopausal osteoporosis.Zan believed that the main etiology and pathogenesis of perimenopausal osteoporosis were "deficiency of kidney essence,decreased marrow and bone",deficiency of liver and kidney"and"stasis caused by deficiency".Although it is a chronic physiological disease,and the pathological process is irreversible,the treatment groups of"tonifying kidney and filling essence","tonifying liver and tonifying kidney"and "tonifying deficiency and promoting blood circulation" can significantly improve the symptoms of patients,slow down the progress of the disease and improve the quality of life of patients.
基金supported by the National Key R&D Program of China(Grant No.2022YFA1504000)the National Natural Science Foundation of China(Grant Nos.12088101,U2230402)+1 种基金the Tianjin Natural Science Foundation(Grant No.20JCZDJC00750)the Deutsche Forschungsgemeinschaft(DFG)(Grant No.EXC 2077)。
文摘The interlayer hybridization(IH)of van der Waals(vdW)materials is thought to be mostly associated with the unignorable interlayer overlaps of wavefunctions(t)in real space.Here,we develop a more fundamental understanding of IH by introducing a new physical quantity,the IH admixture ratioα.Consequently,an exotic strategy of IH engineering in energy space can be proposed,i.e.,instead of changing t as commonly used,αcan be effectively tuned in energy space by changing the on-site energy difference(2Δ)between neighboring-layer states.In practice,this is feasible via reshaping the electrostatic potential of the surface by deposing a dipolar overlayer,e.g.,crystalline ice.Our first-principles calculations unveil that IH engineering via adjusting 2Δcan greatly tune interlayer optical transitions in transition-metal dichalcogenide bilayers,switch different types of Dirac surface states in Bi_(2)Se_(3)thin films,and control magnetic phase transition of charge density waves in 1H/1T-TaS_(2)bilayers,opening new opportunities to govern the fundamental optoelectronic,topological,and magnetic properties of vdW systems beyond the traditional interlayer distance or twisting engineering.
基金the financial support from the National Key Research and Development Program of China(2019YFE0123400 and 2022YFE0114800)the Excellent Young Scholar Fund from the National Natural Science Foundation of China (22122903)+4 种基金the Tianjin Distinguished Young Scholar Fund (20JCJQJC00260)the Major Science and Technology Project of Anhui Province(202203f07020007)Anhui Conch Group Co.,Ltd.the financial support from the National Natural Science Foundation of China (22309089)the project funded by China Postdoctoral Science Foundation (2023M731800)。
文摘Co-electrolysis of waste plastics and carbon dioxide(CO_(2)) into value-added chemicals or fuels is a promising pathway for a sustainable society, but efficient and selective conversion remains a challenge. Herein, a gold-mediated nickel hydroxide(Au/Ni(OH)_(2)) is developed to oxidize waste plastic-derived ethylene glycol(EG) into formate. In-situ electrochemical experiments and theoretical results reveal that the introduction of Au favors the redox properties and EG adsorption behavior of Ni(OH)_(2). The Au/Ni(OH)_(2) catalyst shows an excellent formate selectivity of >90% at high current densities of above 100 m A cm^(-2). When coupled with sputtered bismuth(Bi) cathode for CO_(2) reduction, a high formate Faradic efficiency(FE) of 188.2% at 200 m A cm^(-2)and a good formate productivity of 7.33 mmol m^(-2)s^(-1)at 10 A are obtained in a flow cell and a zero-gap membrane electrode assembly(MEA) cell, respectively. This work demonstrates a promising strategy to convert waste plastics and CO_(2) into valuable products.
基金supported by National Key Research and Development Program (2022YFA1206100, China)Natural Science Foundation of Beijing Municipality (L212013, China)+1 种基金AI+Health Collaborative Innovation Cultivation Project (Z211100003521002,China)National Natural Science Foundation of China(82073786, 81872809, U20A20412, 81821004)
文摘Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.
文摘After converting cropland to forest, carbon Is sequestered in the aggradlng blomass of the new forests, but the question remains, to what extent will the former arable soil contribute as a sink for CO2? Quantifying changes In soil carbon Is an Important consideration In the large-scale conversion of cropland to forest. Extensive field studies were undertaken to Identify a number of suitable sites for comparison of soil properties under pasture and forest. The present paper describes results from a study of the effects of first rotation larch on soil carbon In seven stands In an afforestation chronosequence compared with adjacent Korean pine, pasture, and cropland. An adjacent 250-year-old natural forest was Included to give Information on the possible long-term changes In soil carbon In northeast China In 2004. Soil carbon Initially decreased during the first 12 yr before a gradual recovery and accumulation of soil carbon occurred. The Initial (0-12 yr) decrease In soil carbon was an average 1.2% per year among case studies, whereas the Increase In soil carbon (12-33 yr) was 1.90% per year. Together with the carbon sequestration of forest floors, this led to total soil carbon stores of approximately 101.83 Mg/hm^2 over the 33-year chronosequence. Within the relatively short time span, carbon sequestration occurred mainly In tree blomees, whereas soil carbon stores were clearly higher In the 250-year-old plantation (184 Mg/hm^2). The ongoing redistribution of mineral soil carbon In the young stands and the higher soil carbon contents In the 250-year-old afforested stand suggest that nutrient-rich afforestation soils may become greater sinks for carbon (C) In the long term.
基金supported by the National Key Research and Development Program of China(No.2016YFA0201402)the National Major Scientific and Technological Special Project for“Significant New Drugs Development”of China(No.2018ZX09733001)by the Excellent Youth Foundation of Sichuan Scientific Committee Grant in China(No.2019JDJQ008).
文摘Tumor-associated macrophages(TAMs)facilitate cancer progression by promoting tumor invasion,angiogenesis,metastasis,inflammatory responses,and immunosuppression.Folate receptorβ(FRβ)is overexpressed in TAMs.However,the clinical significance of FRβ-positive macrophages in lung cancer remains poorly understood.In this study,we verified that FRβoverexpression in lung cancer TAMs was associated with poor prognosis.We utilized a folate-modified lipoplex comprising a folatemodified liposome(F-PLP)delivering a BIM-S plasmid to target both lung cancer cells and FRβ-positive macrophages in the tumor microenvironment.Transfection of LL/2 cells and MH-S cells with F-PLP/pBIM induced cell apoptosis.Injection of F-PLP/pBIM into LL/2 and A549 lung cancer models significantly depleted FRβ-positive macrophages and reduced tumor growth.Treatment of tumor-bearing mice with F-PLP/pBIM significantly inhibited tumor growth in vivo by inducing tumor cell and macrophage apoptosis,reducing tumor proliferation,and inhibiting tumor angiogenesis.In addition,a preliminary safety evaluation demonstrated a good safety profile of F-PLP/pBIM as a gene therapy administered intravenously.This work describes a novel application of lipoplexes in lung cancer targeted therapy that influences the tumor microenvironment by targeting TAMs.
基金financially supported by the National Natural Science Foundation of China (No. 51775137)。
文摘Rotationally symmetric workpieces of Ti_(2)AlNb-based alloys have great potential for high-temperature service condition in aviation industry,while the poor workability limits their application until now.In this study,shear spinning and heat treatment were first conducted to investigate the corresponding microstructure evolution and mechanical properties of Ti_(2)AlNb conical workpieces.The microstructure of the 1^(st) and 2^(nd) pass spun workpieces(SP1 and SP2)mainly consisted of B2+retainedα2phases.After two passes spinning,the B2 phase texture changed from<111>//ND of as-received alloy to be<001>//ND.The ultimate tensile stress(UTS)of SP1 and SP2 was increased to 1163 MPa and 932 MPa,respectively,compared with 782 MPa of as-received alloy at 650℃.Also,the yield stress anomaly(YSA)occurred in SP1 and SP2 because{110}<111>and{112}<111>cross slip systems of B2 phase were difficult to slip at or below room temperature(RT),but they became active at 650℃ and above.As an essential step for increasing the spinnability of multi-pass spinning process of the Ti_(2)AlNb alloy,the H3heat treatment scheme,i.e.960℃/2 h+850℃/12 h,was carried out between two successive passes to increase the hot workability,by which the ductility of the heat treated as-spun workpieces with the microstructure of B2+primary O+acicular secondary O+high amount spheroidizedα2phases reached 72.1%at 900℃.After being subject to the H1 heat treatment scheme,i.e.960℃-2 h,the spun workpieces with the microstructure of B2+primary O+intergranular primaryα2phases achieved an optimized comprehensive mechanical properties both at room temperature and 650℃,which should be chosen as the post-spinning heat treatment process for the service requirement.
基金Supported by Rural and Urban Community Project for Promoting Appropriate Techniques of Fujian Health and Family Planning Administration:2018006
文摘Objective: To observe the effects of fuzhengbutu(strengthening antipathogenic qi and tonifying the earth)acupuncture-moxibustion therapy on walking function in the patients with post-stroke hemiplegia.Methods: A total of 57 patients with hemiplegia after ischemic stroke treated in our hospital from January2018 through to October 2018 were collected as the study objects. According to random number table,they were divided into a treatment group(29 cases) and a control group(28 cases). In the treatment group, the fuzhengbutu acupuncture-moxibustion therapy combined with rehabilitation treatment was adopted. In the control group, the rehabilitation treatment was given. The persistent walking time and pause time in PIERENSTEP gait measurable training and test system as well as the score of Berg balance scale(BBS) were compared between the two groups.Results: In the treatment group, the persistent walking time after treatment 1.47 ±0.28) s was shorter obviously versus before treatment(2.12 ± 0.38)s, indicating the significant difference(P<0.05). The pause time after treatment was not different obviously versus before treatment(P> 0.05). In the control group,the persistent walking time after treatment(1.88 ± 0.22) s was shorter obviously versus before treatment(2.18 ± 0.30)s, indicating the significant difference(P<0.05). The pause time after treatment was not different obviously versus before treatment(P> 0.05). Before treatment, the differences were not significant in the persistent walking time and pause duration in the patients of either group(P>0.05). After treatment, the persistent walking time in the treatment group was shorter obviously than the control group(P<0.05) and the difference in pause time was not significant between the two groups(P>0.05). Before treatment, there was no difference in BBS score between the two groups(P>0.05). In the treatment group, BBS score(42.79 ±2.78) after treatment was higher than(35.86 ±2.64) before treatment, indicating the significant difference(P<0.05). In the control group, BBS score(39.07 ±2.67) after treatment was higher than(35.86 ±2.64) before treatment, indicating the significant difference(P<0.05). In comparison of BBS score after treatment between the two groups, the score in the treatment group was higher than the control group, indicating the significant difference(P<0.05).Conclusion: Based on rehabilitation treatment, Fuzhengbutu acupuncture-moxibustion therapy effectively improves the walking function of the patients with hemiplegia after ischemic stroke.