Carcinoma-associated fibroblasts(CAFs)are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix(ECM).The tumor-associated ECM is characterized ...Carcinoma-associated fibroblasts(CAFs)are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix(ECM).The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase(LOX).Small extracellular vesicles(sEVs)mediate cell-cell communication.However,the interactions between sEVs and the ECM remain unclear.Here,we demonstrated that sEVs released from oral squamous cell carcinoma(OSCC)-derived CAFs induce collagen crosslinking,thereby promoting epithelial-mesenchymal transition(EMT).CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking,and a LOX inhibitor or blocking antibody suppressed this effect.Active LOX(αLOX),but not the LOX precursor,was enriched in CAF sEVs and interacted with periostin,fibronectin,and bone morphogenetic protein-1 on the surface of sEVs.CAF sEV-associated integrinα2β1 mediated the binding of CAF sEVs to collagen I,and blocking integrinα2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I.CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway.Taken together,these findings reveal a novel role of CAF sEVs in tumor ECM remodeling,suggesting a critical mechanism for CAF-induced EMT of cancer cells.展开更多
BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs)in elderly patients with heart failure(HF)with reduced ejection fraction(HErEF)remains unclear.METHODS PubMe...BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs)in elderly patients with heart failure(HF)with reduced ejection fraction(HErEF)remains unclear.METHODS PubMed,Embase,and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials(RCTs)and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients(≥60 years)with HErEF.The primary outcome was all-cause mortality.The secondary outcomes were cardiac mortality,HF hospitalization,and the composite endpoint of mortality or HF hospitalization.A meta-analysis was conducted to generate combined hazard ratio(HR)and 95%CI.RESULTS Seven studies(two RCTs and five observational studies)enrolling 16,634 patients were included.A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality(HR=0.92,95%CI:0.87–0.98,I2=21%)and cardiac mortality(HR=0.93,95%CI:0.85–1.00,I2=15%)but not reduced rates of HF hospitalization(HR=0.94,95%CI:0.88–1.01,I2=0)and the composite endpoint(HR=1.03,95%CI:0.91–1.15,I2=51%).However,the target dose of RASIs was associated with a similar primary outcome(HR=0.85,95%CI:0.64–1.14,I2=0)in a subgroup of very elderly patients>75 years of age.CONCLUSIONS Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs.However,the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients>75 years of age.Future high-quality and adequately powered RCTs are warranted.展开更多
AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the b...AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by mea-suring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoas-say. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of con-tractions (SOF), duration of contractions (SOD), duo-denal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the controlgroup (t = 5.254, 3.438 and 3.527, P < 0.001). SOD of the reflux group was shorter than the control group (t = 2.049, P < 0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t = -2.230 and -2.235, P < 0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastroin-testinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi hypomotility and duodenal-biliary re-flux.展开更多
OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and theantagonism of anticholinergic agents against morphine.METHODS: The action of these drugs on the sphincter of Oddi (SO) was ...OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and theantagonism of anticholinergic agents against morphine.METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means ofcholedochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomlyinto 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded:duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of thesphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive durationof the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine andanticholinergic agents were given intramuscularly.RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increasedsignificantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declinedobviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but inanisodamine, atropine and buscopan groups, they differed insignificantly.CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method forSO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine andbuscopan can antagonize the effect of morphine.展开更多
AIM: To assess the effects of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents on the human Sphincter of Oddi (SO) motility by choledochoscope manometry. METHODS: One hundred and seventy-f...AIM: To assess the effects of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents on the human Sphincter of Oddi (SO) motility by choledochoscope manometry. METHODS: One hundred and seventy-five patients with T tube installed after cholecystectomy and choledochotomy were assessed by choledochoscope manometry. They were randomly assigned into groups of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents. The Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duodenal pressure (DP), and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: SOBP and SOCA were significantly decreased after Cimetidine administration, and no statistical difference was seen in the Famotidine group. In the Gabexate mesilate group, SOBP had decreased significantly. In the Ulinastatin group, SOCA decreased when Ulinastatin was given at the rate of 2500 U/min; when Ulinastatin administration was raised to 5000 U/ min, SOBP, SOF and SOCA all experienced a fall. SOBP and SOCA for Domperidone and SOCA for Mosapride groups all decreased distinctly after administration. CONCLUSION: The regular dosage of Cimetidine showed an inhibitory effect on the motility of SO, whileFamotidine had no obvious effects otherwise. Gabnexata mesilate, Ulinastatin and gastro kinetic agents also showed inhibitory effects on the SO motility.展开更多
Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a m...Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a model of Down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neurotrophic factor(BDNF) and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX^+ neurons in the granular layer and NeuN^+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65 Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.展开更多
Objective:To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides(LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of acti...Objective:To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides(LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action.Methods:Total flavonoids from Saussurea involucrata were extracted using chromatographic column method.Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay.The production of nitric oxide was detected by Griess assay and the release of cytokines(IL-10 and TNF-α)and chemokines(MCP-1,MIP-1α,and CCL5/RANTES)was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata.Moreover,nuclear translocation of p65,c-Jun,and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins.Results:Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g.The production of inflammatory mediators including nitric oxide,cytokines,and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata.Meanwhile,total flavonoids also suppressed the nuclear translocation of p65,c-Jun,and IRF3 in LPS-stimulated RAW264.7 cells.The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata.Moreover,total flavonoids decreased the expression levels of p-IKKα/β,p-TBK1,p-p38,p-ERK,p-JNK,p-p65,p-c-Jun,and p-IRF3 in LPS-exposed RAW264.7 macrophages.Conclusions:Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators,which may be related to inhibition of p65,c-Jun,and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.展开更多
Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intraut...Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.展开更多
Highly thermo-conductive aqueous medium is a crucial premise to demonstrate high-performance thermal-related applications.Graphene has the diamond comparable thermal conductivity,while the intrinsic two-dimensional re...Highly thermo-conductive aqueous medium is a crucial premise to demonstrate high-performance thermal-related applications.Graphene has the diamond comparable thermal conductivity,while the intrinsic two-dimensional reality will result in strong anisotropic thermal conductivity and wrinkles or even crumples that significantly sacrifices its inherent properties in practical applications.One strategy to overcome this is to use three-dimensional(3D)architecture of graphene.Herein,3D graphene structure with covalent-bonding nanofins(3D-GS-CBF)is proposed,which is then used as the filler to demonstrate effective aqueous medium.The thermal conductivity and thermal conductivity enhancement efficiency of 3D-GS-CBF(0.26 vol%)aqueous medium can be as high as 2.61 W m-1 K-1 and 1300%,respectively,around six times larger than highest value of the existed aqueous mediums.Meanwhile,3D-GS-CBF can be stable in the solution even after 6 months,addressing the instability issues of conventional graphene networks.A multiscale modeling including non-equilibrium molecular dynamics simulations and heat conduction model is applied to interpret experimental results.3D-GS-CBF aqueous medium can largely improve the solar vapor evaporation rate(by 1.5 times)that are even comparable to the interfacial heating system;meanwhile,its cooling performance is also superior to commercial coolant in thermal management applications.展开更多
[Objectives] To study the effects of Panax ginseng,Codonopsis pilosula and Pseudostellaria heterophylla on the growth and development of SD female rats. [Methods] The rats were randomly divided into control group,P. g...[Objectives] To study the effects of Panax ginseng,Codonopsis pilosula and Pseudostellaria heterophylla on the growth and development of SD female rats. [Methods] The rats were randomly divided into control group,P. ginseng group,C. pilosula group,and P. heterophylla group,intragastrically administered with physiological saline,P. ginseng,C. pilosula,and P. heterophylla for 2 weeks,daily vaginal smear inspection was performed,estradiol( E_2) level before and after intervention was detected,rats were dissected,took out ovary and uterus,and calculated the ovarian index and uterus index. [Results]In 4 groups of rats,there was no significant difference in the time of sexual maturity and ovarian index; compared with the control group,E_2 level of C. pilosula group and P. ginseng group were higher( P < 0. 05);compared with the control group and P. heterophylla group,the ovarian index of P. ginseng group was higher( P < 0. 05); compared with the control group,the body weight of three administration groups increased much more( P < 0. 05). [Conclusions] P. ginseng and C. pilosula may lead to sexual maturity of SD female rats,while P. ginseng,C. pilosula and P. heterophylla can promote increase of body weight of SD female rats.展开更多
A hemocholecyst (HC) is a clot-filled gallbladder caused by bleeding into its lumen. Obstructive jaundice caused by the compression of HC to the hilar biliary tract is likely to be misdiagnosed as cholangiocarcinoma a...A hemocholecyst (HC) is a clot-filled gallbladder caused by bleeding into its lumen. Obstructive jaundice caused by the compression of HC to the hilar biliary tract is likely to be misdiagnosed as cholangiocarcinoma and is extremely rare. We herein report a case of obstructive jaundice and melena caused by HC. A 57-year-old male patient presented with right upper quadrant pain associated with icteric sclera and melena was suspiciously diagnosed as having malignant cholangiocarcinmoa by abdominal ultrasonography, computed tomography and magnetic resonance imaging. Laparotomy found a hematoma in the gallbladder. The hematoma spread to the left hepatic lobe forming an exogenous mass which compressed the hilar biliary tract. Radical cholecystectomy and bile duct exploration with T-tube drainage were performed. Histopathological examination revealed massive necrosis of the gallbladder mucosa with inflammatory cells infiltration as well as intraluminal hematoma formation. One month after operation, a T-tube cholangiography revealed a normal biliary tree. We suggest that HC should be considered in patients with obstructive jaundice and melena after common causes are ruled out.展开更多
To improve the efficiency of cathodic oxygen reduction reaction(ORR)in zinc-air batteries(ZABs),an adsorption-complexation-calcination method was proposed to generate cobalt-based multicomponent nanoparticles comprisi...To improve the efficiency of cathodic oxygen reduction reaction(ORR)in zinc-air batteries(ZABs),an adsorption-complexation-calcination method was proposed to generate cobalt-based multicomponent nanoparticles comprising Co,Co_(3)O_(4)and CoN,as well as numerous N heteroatoms,on graphene nanosheets(Co/Co_(3)O_(4)/CoN/NG).The Co/Co_(3)O_(4)/CoN nanoparticles with the size of less than 50 nm are homogeneously dispersed on N-doped graphene(NG)substrate,which greatly improve the catalytic behaviors for ORR.The results show that the half-wave potential is as high as 0.80 V vs.RHE and the limiting current density is 4.60 mA·cm^(−2),which are close to those of commercially available platinum/carbon(Pt/C)catalysts.Applying as cathodic catalyst for ZABs,the battery shows large specific capacity and open circuit voltage of 843.0 mAh∙g^(−1) and 1.41 V,respectively.The excellent performance is attributed to the efficient two-dimensional structure with high accessible surface area and the numerous multiple active sites provided by highly scattered Co/Co_(3)O_(4)/CoN particles and doped nitrogen on the carbon matrix.展开更多
Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was esta...Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was established by feeding mice a high-fat diet(HFD).After treatment for 30 days,serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were measured with an automatic biochemistry analyzer.The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS.Results:The TC,TG,and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment.A total of 95 compounds from JHEF including 15 phenolic acids(PA),4 phenylethanoid glycosides(PG),24 flavonoids(F),14 triterpenoids(T),10 diterpenoid glycosides(D),18 alkaloids(A)and 10 others(O)were identified.Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang.Furthermore,68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites.The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[a-L-arabinopyranosyl-(1/6)]-b-D-glucopyranoside(PEG)and lirinidine.A total of 43 components from JHFE were absorbed and/or metabolized.The contribution rate of each type of chemical component from JHFE to its lipidlowering effect from high to low were A,F,PG,PA,D and T.Conclusion:The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet(HFD)-induced hyperlipidemia mouse model.Specific types of PA,PG,F,D,T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE.This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.展开更多
Expert Profile:Prof.Douglas R.MacFarlane is an Australian Laureate Fellow at Monash University's School of Chemistry and leader of the Energy Program in the Australian Centre for Electromaterials Science.He is the...Expert Profile:Prof.Douglas R.MacFarlane is an Australian Laureate Fellow at Monash University's School of Chemistry and leader of the Energy Program in the Australian Centre for Electromaterials Science.He is the Australian Academy of Science's Craig Medalist 2018 and winner of the Victoria Prize for Science and Innovation 2018.展开更多
Expert Profile:Prof.Robin D.Rogers is a Research Professor at The University of Alabama and President,Owner,and Founder of 525 Solutions,Inc.,in Tuscaloosa,AL USA.Prof.Robin Rogers is one of the important pioneers in ...Expert Profile:Prof.Robin D.Rogers is a Research Professor at The University of Alabama and President,Owner,and Founder of 525 Solutions,Inc.,in Tuscaloosa,AL USA.Prof.Robin Rogers is one of the important pioneers in the field of ionic liquids from academic research to application.He was awarded the US Presidential Green Chemistry Challenge Award in 2005.展开更多
In recent years, the field of premetastasis niche has attracted more and more attention from international scholars and has become a hot research direction. This article summarizes the current research on the role of ...In recent years, the field of premetastasis niche has attracted more and more attention from international scholars and has become a hot research direction. This article summarizes the current research on the role of the premetastasis niche, the components and formation mechanisms of the premetastasis niche, and the research on the significance of the premetastasis niche to the clinic. Effective cancer diagnosis and treatment strategies are important. A series of research advances in this field are of great significance for further elucidating the mechanism of tumor metastasis and designing more effective cancer diagnosis and treatment strategies.展开更多
基金supported by the National Natural Science Foundation of China(82073001 and 82103423)Shanghai Natural Science Foundation(23ZR1454800)Scientific Research Foundation for the Introduction of Talent in Shanghai Stomatological Hospital(SSDC-2021-RC01).
文摘Carcinoma-associated fibroblasts(CAFs)are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix(ECM).The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase(LOX).Small extracellular vesicles(sEVs)mediate cell-cell communication.However,the interactions between sEVs and the ECM remain unclear.Here,we demonstrated that sEVs released from oral squamous cell carcinoma(OSCC)-derived CAFs induce collagen crosslinking,thereby promoting epithelial-mesenchymal transition(EMT).CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking,and a LOX inhibitor or blocking antibody suppressed this effect.Active LOX(αLOX),but not the LOX precursor,was enriched in CAF sEVs and interacted with periostin,fibronectin,and bone morphogenetic protein-1 on the surface of sEVs.CAF sEV-associated integrinα2β1 mediated the binding of CAF sEVs to collagen I,and blocking integrinα2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I.CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway.Taken together,these findings reveal a novel role of CAF sEVs in tumor ECM remodeling,suggesting a critical mechanism for CAF-induced EMT of cancer cells.
基金This study was supported by the Key R&D Program of Shandong Province(No.2020ZLYS05)。
文摘BACKGROUND The efficiency of the target versus sub-target dose of renin–angiotensin system inhibitors(RASIs)in elderly patients with heart failure(HF)with reduced ejection fraction(HErEF)remains unclear.METHODS PubMed,Embase,and the Cochrane Central Register of Controlled Trials were searched from database inception through March 2022 for randomized controlled trials(RCTs)and observational studies considering the effect of the target versus sub-target dose of RASIs on survival in elderly patients(≥60 years)with HErEF.The primary outcome was all-cause mortality.The secondary outcomes were cardiac mortality,HF hospitalization,and the composite endpoint of mortality or HF hospitalization.A meta-analysis was conducted to generate combined hazard ratio(HR)and 95%CI.RESULTS Seven studies(two RCTs and five observational studies)enrolling 16,634 patients were included.A pooled analysis suggested that the target versus sub-target dose of RASIs led to lower rates of all-cause mortality(HR=0.92,95%CI:0.87–0.98,I2=21%)and cardiac mortality(HR=0.93,95%CI:0.85–1.00,I2=15%)but not reduced rates of HF hospitalization(HR=0.94,95%CI:0.88–1.01,I2=0)and the composite endpoint(HR=1.03,95%CI:0.91–1.15,I2=51%).However,the target dose of RASIs was associated with a similar primary outcome(HR=0.85,95%CI:0.64–1.14,I2=0)in a subgroup of very elderly patients>75 years of age.CONCLUSIONS Our analysis suggests that the target dose of RASIs has a better survival benefit in elderly patients with HFrEF compared to the sub-target dose of RASIs.However,the sub-target dose of RASIs is associated with a similar mortality rate in very elderly patients>75 years of age.Future high-quality and adequately powered RCTs are warranted.
文摘AIM: To detect whether patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux by measuring the radioactivity of Tc99m-labeled diethylene triamine penta-acetic acid (DTPA) in the bile and whether the patients with duodenal-biliary reflux have sphincter of Oddi hypomotility, by mea-suring the level of plasma and serum gastrin of the patients. Finally to if there is close relationship among sphincter of Oddi hypomotility, duodenal-biliary reflux and gastrointestinal peptides. METHODS: Forty-five patients with a T tube after cholecystectomy and choledochotomy were divided into reflux group and control group. The level of plasma and serum gastrin of the patients and of 12 healthy volunteers were measured by radioimmunoas-say. Thirty-four were selected randomly to undergo choledochoscope manometry. Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of con-tractions (SOF), duration of contractions (SOD), duo-denal pressure (DP) and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: Sixteen (35.6%) patients were detected to have duodenal-biliary reflux. SOBP, SOCA and CBDP in the reflux group were much lower than the controlgroup (t = 5.254, 3.438 and 3.527, P < 0.001). SOD of the reflux group was shorter than the control group (t = 2.049, P < 0.05). The level of serum gastrin and plasma motilin of the reflux group was much lower than the control group (t = -2.230 and -2.235, P < 0.05). There was positive correlation between the level of plasma motilin and SOBP and between the level of serum gastrin and SOBP and CBDP. CONCLUSION: About 35.9% of the patients with a T tube after cholecystectomy and choledochotomy have duodenal-biliary reflux. Most of them have sphincter of Oddi hypomotility and the decreased level of plasma motilin and serum gastrin. The disorder of gastroin-testinal hormone secretion may result in sphincter of Oddi dysfunction. There is a close relationship between sphincter of Oddi hypomotility and duodenal-biliary re-flux.
文摘OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and theantagonism of anticholinergic agents against morphine.METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means ofcholedochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomlyinto 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded:duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of thesphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive durationof the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine andanticholinergic agents were given intramuscularly.RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increasedsignificantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declinedobviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but inanisodamine, atropine and buscopan groups, they differed insignificantly.CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method forSO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine andbuscopan can antagonize the effect of morphine.
文摘AIM: To assess the effects of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents on the human Sphincter of Oddi (SO) motility by choledochoscope manometry. METHODS: One hundred and seventy-five patients with T tube installed after cholecystectomy and choledochotomy were assessed by choledochoscope manometry. They were randomly assigned into groups of H2-receptor blocking pharmacon, protease inhibitor, and gastro kinetic agents. The Sphincter of Oddi basal pressure (SOBP), amplitude (SOCA), frequency of contractions (SOF), duodenal pressure (DP), and common bile duct pressure (CBDP) were scored and analyzed. RESULTS: SOBP and SOCA were significantly decreased after Cimetidine administration, and no statistical difference was seen in the Famotidine group. In the Gabexate mesilate group, SOBP had decreased significantly. In the Ulinastatin group, SOCA decreased when Ulinastatin was given at the rate of 2500 U/min; when Ulinastatin administration was raised to 5000 U/ min, SOBP, SOF and SOCA all experienced a fall. SOBP and SOCA for Domperidone and SOCA for Mosapride groups all decreased distinctly after administration. CONCLUSION: The regular dosage of Cimetidine showed an inhibitory effect on the motility of SO, whileFamotidine had no obvious effects otherwise. Gabnexata mesilate, Ulinastatin and gastro kinetic agents also showed inhibitory effects on the SO motility.
基金supported by the Project Funding for the Training of High Level Health Professionals in Changzhou of China,No.2016CZLJ013(to BY)Science and Technology Support Project of Changzhou of China,No.Social Development CE20175021(to BY)Application Basic Research Project of Changzhou of China,No.CJ20160036(to WBZ)
文摘Studies have shown that the natural flavonoid luteolin has neurotrophic activity. In this study, we investigated the effect of luteolin in a mouse model of Down syndrome. Ts65 Dn mice, which are frequently used as a model of Down syndrome, were intraperitoneally injected with 10 mg/kg luteolin for 4 consecutive weeks starting at 12 weeks of age. The Morris water maze test was used to evaluate learning and memory abilities, and the novel object recognition test was used to assess recognition memory. Immunohistochemistry was performed for the neural stem cell marker nestin, the astrocyte marker glial fibrillary acidic protein, the immature neuron marker DCX, the mature neuron marker NeuN, and the cell proliferation marker Ki67 in the hippocampal dentate gyrus. Nissl staining was used to observe changes in morphology and to quantify cells in the dentate gyrus. Western blot assay was used to analyze the protein levels of brain-derived neurotrophic factor(BDNF) and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2) in the hippocampus. Luteolin improved learning and memory abilities as well as novel object recognition ability, and enhanced the proliferation of neurons in the hippocampal dentate gyrus. Furthermore, luteolin increased expression of nestin and glial fibrillary acidic protein, increased the number of DCX^+ neurons in the granular layer and NeuN^+ neurons in the subgranular region of the dentate gyrus, and increased the protein levels of BDNF and p-ERK1/2 in the hippocampus. Our findings show that luteolin improves behavioral performance and promotes hippocampal neurogenesis in Ts65 Dn mice. Moreover, these effects might be associated with the activation of the BDNF/ERK1/2 pathway.
基金This work was supported by the National Natural Science Foundation of China(Grant Number 81803793 and 82003957)the Young Scientist Program by Beijing University of Chinese Medicine,and the Fundamental Research Funds for the Central Universities(Grant Number 2018-JYBZZ-XJSJJ008).
文摘Objective:To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides(LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action.Methods:Total flavonoids from Saussurea involucrata were extracted using chromatographic column method.Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay.The production of nitric oxide was detected by Griess assay and the release of cytokines(IL-10 and TNF-α)and chemokines(MCP-1,MIP-1α,and CCL5/RANTES)was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata.Moreover,nuclear translocation of p65,c-Jun,and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins.Results:Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g.The production of inflammatory mediators including nitric oxide,cytokines,and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata.Meanwhile,total flavonoids also suppressed the nuclear translocation of p65,c-Jun,and IRF3 in LPS-stimulated RAW264.7 cells.The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata.Moreover,total flavonoids decreased the expression levels of p-IKKα/β,p-TBK1,p-p38,p-ERK,p-JNK,p-p65,p-c-Jun,and p-IRF3 in LPS-exposed RAW264.7 macrophages.Conclusions:Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators,which may be related to inhibition of p65,c-Jun,and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.
基金Supported by the National Natural Science Foundation of China(30672237)
文摘Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.
基金the financial support from National Natural Science Foundation of China(No.51906211)the China Postdoctoral Science Foundation(No.2019M662048)+1 种基金the Key R&D Program of Zhejiang Province(No.2019C01044)the Zhejiang Provincial Natural Science Foundation of China(No.LR17E060002)。
文摘Highly thermo-conductive aqueous medium is a crucial premise to demonstrate high-performance thermal-related applications.Graphene has the diamond comparable thermal conductivity,while the intrinsic two-dimensional reality will result in strong anisotropic thermal conductivity and wrinkles or even crumples that significantly sacrifices its inherent properties in practical applications.One strategy to overcome this is to use three-dimensional(3D)architecture of graphene.Herein,3D graphene structure with covalent-bonding nanofins(3D-GS-CBF)is proposed,which is then used as the filler to demonstrate effective aqueous medium.The thermal conductivity and thermal conductivity enhancement efficiency of 3D-GS-CBF(0.26 vol%)aqueous medium can be as high as 2.61 W m-1 K-1 and 1300%,respectively,around six times larger than highest value of the existed aqueous mediums.Meanwhile,3D-GS-CBF can be stable in the solution even after 6 months,addressing the instability issues of conventional graphene networks.A multiscale modeling including non-equilibrium molecular dynamics simulations and heat conduction model is applied to interpret experimental results.3D-GS-CBF aqueous medium can largely improve the solar vapor evaporation rate(by 1.5 times)that are even comparable to the interfacial heating system;meanwhile,its cooling performance is also superior to commercial coolant in thermal management applications.
基金Supported by Scientific Research Foundation of Shanghai Association of Chinese Integrative Medicine(ZXYK-1213)
文摘[Objectives] To study the effects of Panax ginseng,Codonopsis pilosula and Pseudostellaria heterophylla on the growth and development of SD female rats. [Methods] The rats were randomly divided into control group,P. ginseng group,C. pilosula group,and P. heterophylla group,intragastrically administered with physiological saline,P. ginseng,C. pilosula,and P. heterophylla for 2 weeks,daily vaginal smear inspection was performed,estradiol( E_2) level before and after intervention was detected,rats were dissected,took out ovary and uterus,and calculated the ovarian index and uterus index. [Results]In 4 groups of rats,there was no significant difference in the time of sexual maturity and ovarian index; compared with the control group,E_2 level of C. pilosula group and P. ginseng group were higher( P < 0. 05);compared with the control group and P. heterophylla group,the ovarian index of P. ginseng group was higher( P < 0. 05); compared with the control group,the body weight of three administration groups increased much more( P < 0. 05). [Conclusions] P. ginseng and C. pilosula may lead to sexual maturity of SD female rats,while P. ginseng,C. pilosula and P. heterophylla can promote increase of body weight of SD female rats.
文摘A hemocholecyst (HC) is a clot-filled gallbladder caused by bleeding into its lumen. Obstructive jaundice caused by the compression of HC to the hilar biliary tract is likely to be misdiagnosed as cholangiocarcinoma and is extremely rare. We herein report a case of obstructive jaundice and melena caused by HC. A 57-year-old male patient presented with right upper quadrant pain associated with icteric sclera and melena was suspiciously diagnosed as having malignant cholangiocarcinmoa by abdominal ultrasonography, computed tomography and magnetic resonance imaging. Laparotomy found a hematoma in the gallbladder. The hematoma spread to the left hepatic lobe forming an exogenous mass which compressed the hilar biliary tract. Radical cholecystectomy and bile duct exploration with T-tube drainage were performed. Histopathological examination revealed massive necrosis of the gallbladder mucosa with inflammatory cells infiltration as well as intraluminal hematoma formation. One month after operation, a T-tube cholangiography revealed a normal biliary tree. We suggest that HC should be considered in patients with obstructive jaundice and melena after common causes are ruled out.
基金financially supported by the National Natural Science Foundation of China (No. 52102100)the Industry-University-Research Cooperation Project of Jiangsu Province, China (No. BY2021525)the Postgraduate Research & Practice Innovation Program of Jiangsu Province, China (No. SJCX22_1944)
文摘To improve the efficiency of cathodic oxygen reduction reaction(ORR)in zinc-air batteries(ZABs),an adsorption-complexation-calcination method was proposed to generate cobalt-based multicomponent nanoparticles comprising Co,Co_(3)O_(4)and CoN,as well as numerous N heteroatoms,on graphene nanosheets(Co/Co_(3)O_(4)/CoN/NG).The Co/Co_(3)O_(4)/CoN nanoparticles with the size of less than 50 nm are homogeneously dispersed on N-doped graphene(NG)substrate,which greatly improve the catalytic behaviors for ORR.The results show that the half-wave potential is as high as 0.80 V vs.RHE and the limiting current density is 4.60 mA·cm^(−2),which are close to those of commercially available platinum/carbon(Pt/C)catalysts.Applying as cathodic catalyst for ZABs,the battery shows large specific capacity and open circuit voltage of 843.0 mAh∙g^(−1) and 1.41 V,respectively.The excellent performance is attributed to the efficient two-dimensional structure with high accessible surface area and the numerous multiple active sites provided by highly scattered Co/Co_(3)O_(4)/CoN particles and doped nitrogen on the carbon matrix.
基金the innovative research team of the Twelfth Five-Year National Science and Technology Support Program(Grant no.2012BAI29B06)the Beijing University of Chinese Medicine of China(Grant no.2011-CXTD-12).
文摘Objective:The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract(JHFE)and to determine its characteristic chemical profile in vitro and in vivo.Methods:A hyperlipidemia model was established by feeding mice a high-fat diet(HFD).After treatment for 30 days,serum total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were measured with an automatic biochemistry analyzer.The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS.Results:The TC,TG,and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment.A total of 95 compounds from JHEF including 15 phenolic acids(PA),4 phenylethanoid glycosides(PG),24 flavonoids(F),14 triterpenoids(T),10 diterpenoid glycosides(D),18 alkaloids(A)and 10 others(O)were identified.Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang.Furthermore,68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites.The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[a-L-arabinopyranosyl-(1/6)]-b-D-glucopyranoside(PEG)and lirinidine.A total of 43 components from JHFE were absorbed and/or metabolized.The contribution rate of each type of chemical component from JHFE to its lipidlowering effect from high to low were A,F,PG,PA,D and T.Conclusion:The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet(HFD)-induced hyperlipidemia mouse model.Specific types of PA,PG,F,D,T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE.This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.
文摘Expert Profile:Prof.Douglas R.MacFarlane is an Australian Laureate Fellow at Monash University's School of Chemistry and leader of the Energy Program in the Australian Centre for Electromaterials Science.He is the Australian Academy of Science's Craig Medalist 2018 and winner of the Victoria Prize for Science and Innovation 2018.
文摘Expert Profile:Prof.Robin D.Rogers is a Research Professor at The University of Alabama and President,Owner,and Founder of 525 Solutions,Inc.,in Tuscaloosa,AL USA.Prof.Robin Rogers is one of the important pioneers in the field of ionic liquids from academic research to application.He was awarded the US Presidential Green Chemistry Challenge Award in 2005.
文摘In recent years, the field of premetastasis niche has attracted more and more attention from international scholars and has become a hot research direction. This article summarizes the current research on the role of the premetastasis niche, the components and formation mechanisms of the premetastasis niche, and the research on the significance of the premetastasis niche to the clinic. Effective cancer diagnosis and treatment strategies are important. A series of research advances in this field are of great significance for further elucidating the mechanism of tumor metastasis and designing more effective cancer diagnosis and treatment strategies.
