BACKGROUND Heterogeneous macrophages play an important role in multiple liver diseases,including viral fulminant hepatitis(VFH).Fibrinogen-like protein 2(FGL2)is expressed on macrophages and regulates VFH pathogenesis...BACKGROUND Heterogeneous macrophages play an important role in multiple liver diseases,including viral fulminant hepatitis(VFH).Fibrinogen-like protein 2(FGL2)is expressed on macrophages and regulates VFH pathogenesis;however,the underlying mechanism remains unclear.AIM To explore how FGL2 regulates macrophage function and subsequent liver injury during VFH.METHODS Murine hepatitis virus strain 3(MHV-3)was used to induce VFH in FGL2-deficient(Fgl2-/-)and wild-type(WT)mice.The dynamic constitution of hepatic macrophages was examined.Adoptive transfer of Fgl2-/-or WT bone marrowderived macrophages(BMDMs)into WT recipients with macrophages depleted prior to infection was carried out and the consequent degree of liver damage was compared.The signaling cascades that may be regulated by FGL2 were detected in macrophages.RESULTS Following MHV-3 infection,hepatic macrophages were largely replenished by proinflammatory monocyte-derived macrophages(MoMFs),which expressed high levels of FGL2.In Fgl2-/-mice,the number of infiltrating inflammatory MoMFs was reduced compared with that in WT mice after viral infection.Macrophage depletion ameliorated liver damage in WT mice and further alleviated liver damage in Fgl2-/-mice.Adoptive transfer of Fgl2-/-BMDMs into macrophage-removed recipients significantly reduced the degree of liver damage.Inhibition of monocyte infiltration also significantly ameliorated liver damage.Functionally,Fgl2 deletion impaired macrophage phagocytosis and the antigen presentation potential and attenuated the proinflammatory phenotype.At the molecular level,FGL2 deficiency impaired IRF3,IRF7,and p38 phosphorylation,along with NF-κB activation in BMDMs in response to viral infection.CONCLUSION Infiltrated MoMFs represent a major source of hepatic inflammation during VFH progression,and FGL2 expression on MoMFs maintains the proinflammatory phenotype via p38-dependent positive feedback,contributing to VFH pathogenesis.展开更多
Background:Protein tyrosine kinase 6(PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis.However,PTK6 expression status and its role in cervical squamous cell cancer are unknown.This study aim...Background:Protein tyrosine kinase 6(PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis.However,PTK6 expression status and its role in cervical squamous cell cancer are unknown.This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen,early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues.The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed,paraffin-embedded,early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections.Results:The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues.Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells.The level of PTK6 expression was significantly associated with tumor grade(P = 0.020).The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression(81.3%vs.96.2%,P = 0.008).Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival(hazard ratio = 5.999,95%confidence interval 1.622-22.191,P< 0.05).Conclusions:PTK6 is overexpressed in cervical squamous ceil cancer.Increased PTK6 expression is associated with reduced 5-year overall survival.PTK6 expression is an independent prognostic predictor for cervical cancer.展开更多
The role of chemokines in murine hepatitis virus strain 3 (MHV-3) induced fulminant hepatic failure (FHF) is not well defined. In this study, we investigated the role of the CXC chemokine receptor 3 (CXCR3)- associate...The role of chemokines in murine hepatitis virus strain 3 (MHV-3) induced fulminant hepatic failure (FHF) is not well defined. In this study, we investigated the role of the CXC chemokine receptor 3 (CXCR3)- associated chemokine [monokine induced by IFN-gamma (Mig/CXCL9) and interferon-gamma-inducible protein 10 (IP-10/CXCL10)] in the recruitment of intrahepatic lymphocytes and subsequent fulminant hepatic failure induced by MHV-3. Balb/cJ mice (6-8 weeks, female) were intraperitioneally injected with 100 PFU MHV-3.The proportions and numbers of T cells and NK cells as well as the expression of CXCR3 on T cells and NK cells in the liver, spleen and blood were analyzed by flow cytometry. The hepatic mRNA level of the CXCR3-associated chemokines (CXCL9 and CXCL10) was detected by realtime PCR. A transwell migration assay was used to assess the chemotactic effect of MHV-3-infected hepatocytes on the splenic lymphocytes. Following MHV-3 infection, the number of hepatic NK cells and T cells and the frequencies of hepatic NK cells and T cells expressing CXCR3 increased markedly; however, in the spleen and peripheral blood, they both decreased significantly. Moreover, the hepatic mRNAs levels of CXCL9 and CXCL10 were significantly elevated post infection. The transwell migration assay demonstrated that MHV-3-infected hepatocytes have the capacity to attract and recruit the splenic NK cells and T cells, and CXCL10 plays a key role in lymphocyte mobilization from the spleen. These results suggest that the CXCR3- associated chemokines (CXCL9 and CXCL10) may play animportant role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and hepatic failure in MHV-3 infection.展开更多
AIM:To assess and teach cultural competency skills at the fellowship training level through the use of objective structured clinical examinations(OSCEs).METHODS:We revised four scenarios to infuse a specific focus on ...AIM:To assess and teach cultural competency skills at the fellowship training level through the use of objective structured clinical examinations(OSCEs).METHODS:We revised four scenarios to infuse a specific focus on cross-cultural care,and to render them appropriate for gastroenterology fellows.Three are discussed here:(1)Poor Health Literacy;(2)Disclosing/Apologizing for a Complication to a Patient Who Mistrusts the Healthcare System;and(3)Breaking Bad News to a Fatalistic Patient.A fourth case emphasizing shared decision-making will be described elsewhere.Four stations were completed by fellows and observed live by four faculty members,and the fellows’performance was assessed.RESULTS:Eleven fellows from four programs participated in the four OSCE.In the"Poor Health Literacy"case,18%(2/11)of participants recognized that the standardized patient(SP)had below-basic health literacy.None successfully evaluated the SP’s reading skills in a culturally-sensitive manner.In"Disclosing/Apologizing for a Complication",4/11(36%)personally apologized for the complication.1/11 recognized the SP’s mistrust of the medical system.With"Breaking Bad News",27%(3/11)explored the patient’s values to identify her fatalistic beliefs.CONCLUSION:OSCEs can be used to assess deficiencies in culturally-competent care at the fellowship level.OSCEs also afford fellowships the opportunity to inform future training curricula.展开更多
The development of metal sulfide catalysts with remarkable activity toward efficient overall photocatalytic water splitting remains challenging owing to the dominant charge recombination and deficient catalytic active...The development of metal sulfide catalysts with remarkable activity toward efficient overall photocatalytic water splitting remains challenging owing to the dominant charge recombination and deficient catalytic active sites.Moreover,in the process of water oxidation catalysis,the inhibition of severe photocorrosion is an immense task,requiring effective photogenic hole-transfer kinetics.Herein,stratified Co-MnO_(2)@CdS/CoS hollow cubes with spatially separated catalytic sites were rationally designed and fabricated as highly efficient controllable catalysts for photocatalytic overall water splitting.The unique self-templated method,including a continuous anion/cation-exchange reaction,integrates a Co-doped oxidation co-catalyst(Co-MnO_(2))and a reduction co-catalyst(CoS)on the nanocubes with uniform interface contact and ultrathin two-dimensional(2D)nanometer sheets.We demonstrate that the stratified Co-MnO_(2)@CdS/CoS hollow cubes can provide an abundance of active sites for surface redox reactions and contribute to the separation and migration of the photoionization charge carriers.In particular,CoS nanoparticles dispersed on the walls of CdS hollow cubes were identified as reduction co-catalysts accelerating hydrogen generation,while Co-MnO_(2) nanosheets attached to the inner walls of the CdS hollow cube were oxidation co-catalysts,promoting oxygen evolution dynamics.Benefiting from the desirable structural and compositional advantages,optimized stratification of Co-MnO_(2)@CdS/CoS nanocubes provided a catalytic system devoid of precious metals,which exhibited a remarkable overall photocatalytic water-splitting rate(735.4(H_(2))and 361.1(O_(2))μmol h^(−1) g^(−1)),being among the highest values reported thus far for CdS-based catalysts.Moreover,an apparent quantum efficiency(AQE)of 1.32%was achieved for hydrogen evolution at 420 nm.This study emphasizes the importance of rational design on the structure and composition of photocatalysts for overall water splitting.展开更多
To assess first-year gastroenterology fellows’ ability to address difficult interpersonal situations in the workplace using objective structured clinical examinations (OSCE).METHODSTwo OSCEs (“distracted care team”...To assess first-year gastroenterology fellows’ ability to address difficult interpersonal situations in the workplace using objective structured clinical examinations (OSCE).METHODSTwo OSCEs (“distracted care team” and “frazzled intern”) were created to assess response to disruptive behavior. In case 1, a fellow used a colonoscopy simulator while interacting with a standardized patient (SP), nurse, and attending physician all played by actors. The nurse and attending were instructed to display specific disruptive behavior and disregard the fellow unless requested to stop the disruptive behavior and focus on the patient and procedure. In case 2, the fellow was to calm an intern managing a patient with massive gastrointestinal bleeding. The objective in both scenarios was to assess the fellows’ ability to perform their duties while managing the disruptive behavior displayed by the actor. The SPs used checklists to rate fellows’ performances. The fellows completed a self-assessment survey.RESULTSTwelve fellows from four gastrointestinal fellowship training programs participated in the OSCE. In the “distracted care team” case, one-third of the fellows interrupted the conflict and refocused attention to the patient. Half of the fellows were able to display professionalism despite the heated discussion nearby. Fellows scored lowest in the interprofessionalism portion of post-OSCE surveys, measuring their ability to handle the conflict. In the “frazzled intern” case, 68% of fellows were able to establish a calm and professional relationship with the SP. Despite this success, only half of the fellows were successfully communicate a plan to the SP and only a third scored “well done” in a domain that focused on allowing the intern to think through the case with the fellow’s guidance.CONCLUSIONFellows must receive training on how to approach disruptive behavior. OSCEs are a tool that can assess fellow skills and set a culture for open discussion.展开更多
In order to consider the influence of the continuous rotary motor electro-hydraulic servo system parameters change on its performance,the design method of backstepping adaptive controller is put forward.The mathematic...In order to consider the influence of the continuous rotary motor electro-hydraulic servo system parameters change on its performance,the design method of backstepping adaptive controller is put forward.The mathematical model of electro-hydraulic servo system of continuous rotary motor is established,and the whole system is decomposed into several lower order subsystems,and the virtual control signal is designed for each subsystem from the final subsystem with motor angular displacement to the subsystem with system control input voltage. Based on Lyapunov method and the backstepping theory,an adaptive backstepping controller is designed with the changed parameters adaptive law. It is proved that the system reaches the global asymptotic stability,and the system tracking error asymptotically tends to zero. The simulation results show that the backstepping adaptive controller based on the adaptive law of the changed parameters can improve the performance of continuous rotary motor,and the proposed control strategy is feasible.展开更多
Objective:To evaluate the effect of individualized nutritional intervention therapy in patients with gestational diabetes mellitus(GDM).Methods:80 GDM inpatients admitted to the First Affiliated Hospital of Hainan Med...Objective:To evaluate the effect of individualized nutritional intervention therapy in patients with gestational diabetes mellitus(GDM).Methods:80 GDM inpatients admitted to the First Affiliated Hospital of Hainan Medical College from December 2015 to June 2018 were enrolled.According to the random number table method,the patients were divided into 4 groups,with 20 cases in each group.Group 1 used food exchange combined glycemic index method,group 2 used food exchange combined blood glucose load method,group 3 used glycemic index combined with blood glucose load method,group 4 combined glycemic index and blood glucose load method based on food exchange.After the intervention,the changes of blood glucose level,biochemical indexes and fetal growth and development indexes of the four groups were observed.Results:After nutritional intervention,the blood glucose levels of the four groups of patients decreased to varying degrees compared with before the intervention.The difference was statistically significant(P<0.05).In order to evaluate the advantages and disadvantages of the four methods,the blood glucose levels of the four groups of patients were further compared between groups:compared with group 1,group 2,group 4 and group 3,the differences were statistically significant(P<0.01 or 0.05).There was significant difference in blood glucose 2 hours after dinner between group 4 and group 1 and group 2(P<0.05).Comparing the biochemical indexes and fetal growth and development indexes of the four groups,the differences were not statistically significant(P>0.05).Conclusion:Individualized nutritional intervention therapy can significantly improve the blood glucose level of GDM patients,and at the same time meet the needs of the mother's own physiology and fetal growth and development.Among them,the nutrition intervention method that combines the glycemic index and the blood glucose load on the basis of the food exchange portion has a better effect on improving the blood glucose level of the patient.展开更多
The effects of Mn addition(0.005,0.01,0.03,0.05,and 0.07 wt.%)on microstructure,shear mechanical behavior,and interfacial thermal stabilities of SAC305 joints were investigated under isothermal aging temperatures of 1...The effects of Mn addition(0.005,0.01,0.03,0.05,and 0.07 wt.%)on microstructure,shear mechanical behavior,and interfacial thermal stabilities of SAC305 joints were investigated under isothermal aging temperatures of 170 C with different aging time(0,250,500,and 750 h).It is found that Mn addition can increase fracture energy of joints without decreasing the shear strength.And the microstructures have transformed from the eutectic net-like structure in SAC305 solder joints into the structures based onβ-Sn matrix with intermetallic compounds(IMCs)distributed.By doping 0.07 wt.%Mn,the Cu_(6)Sn_(5) growth along the SAC305/Cu interface during thermal aging can be inhibited to some extent.During isothermal aging at 170°C,the maximum shear force of solder joint decreases continuously with aging time increasing,while the fracture energy rises first and then decreases,reaching the maximum at 500 h compared by that with the microstructure homogenization.Cu_(3)Sn growth between Cu_(3)Sn_(5)/Cu interface has been retarded most at the aging time of 250 h with 0.07 wt.%Mn-doped joints.With the aging time prolonging,the inhibition effect of Mn on CusSn IMC layer becomes worse.The strengthening effect of Mn can be explained by precipitation strengthening,and its mechanical behavior can be predicted by particle strengthening model proposed by Orowan.展开更多
Adjusting the interfacial transport efficiency of photogenerated electrons and the free energy of hydrogen adsorption through interface engineering is an effective means of improving the photocatalytic activity of sem...Adjusting the interfacial transport efficiency of photogenerated electrons and the free energy of hydrogen adsorption through interface engineering is an effective means of improving the photocatalytic activity of semiconductor photocatalysts.Herein,hollow ZnS/NiS nanocages with ohmic contacts containing Zn vacancy(V_(Zn)-ZnS/NiS)are synthesized using ZIF-8 as templates.An internal electric field is constructed by Fermi level flattening to form ohmic contacts,which increase donor density and accelerate electron transport at the V_(Zn)-ZnS/NiS interface.The experimental and DFT results show that the tight interface and V_(Zn) can rearrange electrons,resulting in a higher charge density at the interface,and optimizing the Gibbs free energy of hydrogen adsorption.The optimal hydrogen production activity of V_(Zn)-ZnS/NiS is 10,636 mmol h^(-1) g^(-1),which is 31.9 times that of V_(Zn)-ZnS.This study provides an idea for constructing sulfide heterojunctions with ohmic contacts and defects to achieve efficient photocatalytic hydrogen production.展开更多
Chlorophyll fluorescence and antioxidative capability in detached leaves of the wild type Arabidopsis thaliana L. ecotype Landsberg erecta （Ler） and three mutants deficient in anthocyanins biosynthesis （tt3, tt4, a...Chlorophyll fluorescence and antioxidative capability in detached leaves of the wild type Arabidopsis thaliana L. ecotype Landsberg erecta （Ler） and three mutants deficient in anthocyanins biosynthesis （tt3, tt4, and tt3tt4） were investigated during treatment with temperatures ranging 25-45 ℃. In comparison with the wild type, chlorophyll fluorescence parameters Fv/Fm, φps,, electron transport rate （ETR）, Fv/Fo and qP in three anthocyanin-deficient mutants showed a more rapidly decreasing rate when the temperature was over 35 ℃. Non-photochemical quenching （NPQ） in these mutants was almost completely lost at 44 ℃, whereas the content of heat stable protein dropped and the rate of the membrane leakage increased. Fo-temperature curves were obtained by monitoring Fo levels with gradually elevated temperatures from 22 ℃ to 72 ℃ at 0.5 ℃/min. The inflexion temperatures of Fo were 45.8 ℃ in Ler, 45.1℃ in tt3, 44.1℃ in tt4 and 42.3 ℃ in tt3tt4, respectively. The temperatures of maximal Fo in three mutants were 1.9-3.8℃ lower than the wild type plants. Meanwhile, three mutants had lower activities of superoxide dismutase （SOD） and ascorbate peroxidase （APX） and an inferior scavenging capability to DPPH （1.1-diphenyl-2-picrylhy.drazyl） radical under heat stress, and in particular tt3tt4 had the lowest antioxidative potential. The results of the diaminobenzidine-H2O2 histochemical staining showed that H2O2 was accumulated in the leaf vein and mesophyll cells of mutants under treatment at 40 ℃, and it was significantly presented in leaf cells of tt3tt4. The sensitivity of Arabidopsis anthocyanins-deficient mutants to high temperatures has revealed that anthocyanins in normal plants might provide protection from high temperature injury, by enhancing its antioxidative capability under high temperature stress.展开更多
A new sesquiterpene lactone(1)and a new aromatic glycoside(2),together with three known compounds(3–5)were isolated from the stem bark of Illicium difengpi K.I.B et K.I.M.Their structures were determined by spectrosc...A new sesquiterpene lactone(1)and a new aromatic glycoside(2),together with three known compounds(3–5)were isolated from the stem bark of Illicium difengpi K.I.B et K.I.M.Their structures were determined by spectroscopic methods,including 1D and 2D NMR,HRESIMS,and chemical methods.The absolute configuration of the secondary alcohol in 1 was confirmed by Mosher’s method.Compound 2 exhibited significant anti-inflammatory activity with IC50 value of 6.72 mmol/L.展开更多
Oral mucositis, a severe oral ulceration, is a common toxic effect of radioor chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at l...Oral mucositis, a severe oral ulceration, is a common toxic effect of radioor chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body radiation, develop oral mucositis. To date, there is no FDA approved drug to treat oral mucositis in cancer patients. The key challenges for oral mucositis treatment are to repair and protect ulcerated oral mucosa without promoting cancer cell growth. Oral mucositis is the result of complex, multifaceted pathobiology, involving a series of signaling pathways and a chain of interactions between the epithelium and submucosa. Among those pathways and interactions, the activation of nuclear factor-kappa B （NF-KB） is critical to the inflamma- tion process of oral mucositis. We recently found that activation of TGFβ （transforming growth factor β） signaling is associated with the development of oral mucositis. Smad7, the negative regulator of TGFβ signaling, inhibits both NF-KB and TGFβ activation and thus plays a pivotal role in the prevention and treatment of oral mucositis by attenuating growth inhibition, apoptosis, and inflammation while promoting epithelial migration. The major objective of this review is to evaluate the known functions of Smad7, with a particular focus on its molecular mechanisms and its function in blocking multiple pathological processes in oral mucositis.展开更多
In this paper,a model of mumps transmission with quarantine measure is proposed and then the control reproduction number Rc of the model is obtained.This model admits a unique endemic equilibrium P*if and only if Rc&g...In this paper,a model of mumps transmission with quarantine measure is proposed and then the control reproduction number Rc of the model is obtained.This model admits a unique endemic equilibrium P*if and only if Rc>1,while the disease-free equilibrium P0 always exists.By using the technique of constructing Lyapunov functions and the generalized Lyapunov-LaSalle theorem,we first show that the equilibrium P0 is globally asymptotically stable(GAS)if Rc≤1;second,we prove that the equilibrium P*is GAS if Rc>1.Our results reveal that mumps can be eliminated from the community for Rc≤1 and it will be persistent for Rc>1,and quarantine measure can also effectively control the mumps transmission.展开更多
One new sesquiterpene compound, namely, illihenlactone A（1）, and one new prenylated C6–C3 compound, illihenryione H（2）, along with three known sesquiterpenes（3–5） were isolated from the stems of Illicium henry...One new sesquiterpene compound, namely, illihenlactone A（1）, and one new prenylated C6–C3 compound, illihenryione H（2）, along with three known sesquiterpenes（3–5） were isolated from the stems of Illicium henryi. The structures of 1 and 2 were elucidated by spectroscopic evidence including NMR, HRESIMS and circular dichroism（CD）. Compound 2 exhibited a weak inhibitory ratio for bglucuronidase release induced by platelet-activating factor（PAF） in rat polymorphonuclear leukocytes（PMNs） in vitro.展开更多
Background:Coronavirus disease 2019(COVID-19)is a serious and even lethal respiratory illness.The mortality of critically ill patients with COVID-19,especially short term mortality,is considerable.It is crucial and ur...Background:Coronavirus disease 2019(COVID-19)is a serious and even lethal respiratory illness.The mortality of critically ill patients with COVID-19,especially short term mortality,is considerable.It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage,which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.Methods:In this retrospective observational study,we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12,2020.Demographic,clinical and laboratory data were collected and analyzed.A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95%confidence interval for assessing the risk factors for 30-day mortality.Results:The 30-day mortality was 11.8%(112 of 949 patients).Forty-nine point nine percent(474)patients had one or more comorbidities,with hypertension being the most common(359[37.8%]patients),followed by diabetes(169[17.8%]patients)and coronary heart disease(89[9.4%]patients).Age above 50 years,respiratory rate above 30 beats per minute,white blood cell count of more than 10×109/L,neutrophil count of more than 7×109/L,lymphocyte count of less than 0.8×109/L,platelet count of less than 100×109/L,lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19.A predictive CAPRL score was proposed integrating independent risk factors.The 30-day mortality were 0%(0 of 156),1.8%(8 of 434),12.9%(26 of 201),43.0%(55 of 128),and 76.7%(23 of 30)for patients with 0,1,2,3,≥4 points,respectively.Conclusions:We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19.It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.展开更多
基金Supported by the National Science and Technology Major Project,No.2017ZX10202201and the National Natural Science Foundation of China,No.NSFC 81700529。
文摘BACKGROUND Heterogeneous macrophages play an important role in multiple liver diseases,including viral fulminant hepatitis(VFH).Fibrinogen-like protein 2(FGL2)is expressed on macrophages and regulates VFH pathogenesis;however,the underlying mechanism remains unclear.AIM To explore how FGL2 regulates macrophage function and subsequent liver injury during VFH.METHODS Murine hepatitis virus strain 3(MHV-3)was used to induce VFH in FGL2-deficient(Fgl2-/-)and wild-type(WT)mice.The dynamic constitution of hepatic macrophages was examined.Adoptive transfer of Fgl2-/-or WT bone marrowderived macrophages(BMDMs)into WT recipients with macrophages depleted prior to infection was carried out and the consequent degree of liver damage was compared.The signaling cascades that may be regulated by FGL2 were detected in macrophages.RESULTS Following MHV-3 infection,hepatic macrophages were largely replenished by proinflammatory monocyte-derived macrophages(MoMFs),which expressed high levels of FGL2.In Fgl2-/-mice,the number of infiltrating inflammatory MoMFs was reduced compared with that in WT mice after viral infection.Macrophage depletion ameliorated liver damage in WT mice and further alleviated liver damage in Fgl2-/-mice.Adoptive transfer of Fgl2-/-BMDMs into macrophage-removed recipients significantly reduced the degree of liver damage.Inhibition of monocyte infiltration also significantly ameliorated liver damage.Functionally,Fgl2 deletion impaired macrophage phagocytosis and the antigen presentation potential and attenuated the proinflammatory phenotype.At the molecular level,FGL2 deficiency impaired IRF3,IRF7,and p38 phosphorylation,along with NF-κB activation in BMDMs in response to viral infection.CONCLUSION Infiltrated MoMFs represent a major source of hepatic inflammation during VFH progression,and FGL2 expression on MoMFs maintains the proinflammatory phenotype via p38-dependent positive feedback,contributing to VFH pathogenesis.
文摘Background:Protein tyrosine kinase 6(PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis.However,PTK6 expression status and its role in cervical squamous cell cancer are unknown.This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen,early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues.The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed,paraffin-embedded,early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections.Results:The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues.Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells.The level of PTK6 expression was significantly associated with tumor grade(P = 0.020).The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression(81.3%vs.96.2%,P = 0.008).Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival(hazard ratio = 5.999,95%confidence interval 1.622-22.191,P< 0.05).Conclusions:PTK6 is overexpressed in cervical squamous ceil cancer.Increased PTK6 expression is associated with reduced 5-year overall survival.PTK6 expression is an independent prognostic predictor for cervical cancer.
基金the National Key Basic Research Program of China (2007CB512900, 2005CB522901, 2005CB 522507)the National Science Fund of China (NSFC 30672380, 30571643)
文摘The role of chemokines in murine hepatitis virus strain 3 (MHV-3) induced fulminant hepatic failure (FHF) is not well defined. In this study, we investigated the role of the CXC chemokine receptor 3 (CXCR3)- associated chemokine [monokine induced by IFN-gamma (Mig/CXCL9) and interferon-gamma-inducible protein 10 (IP-10/CXCL10)] in the recruitment of intrahepatic lymphocytes and subsequent fulminant hepatic failure induced by MHV-3. Balb/cJ mice (6-8 weeks, female) were intraperitioneally injected with 100 PFU MHV-3.The proportions and numbers of T cells and NK cells as well as the expression of CXCR3 on T cells and NK cells in the liver, spleen and blood were analyzed by flow cytometry. The hepatic mRNA level of the CXCR3-associated chemokines (CXCL9 and CXCL10) was detected by realtime PCR. A transwell migration assay was used to assess the chemotactic effect of MHV-3-infected hepatocytes on the splenic lymphocytes. Following MHV-3 infection, the number of hepatic NK cells and T cells and the frequencies of hepatic NK cells and T cells expressing CXCR3 increased markedly; however, in the spleen and peripheral blood, they both decreased significantly. Moreover, the hepatic mRNAs levels of CXCL9 and CXCL10 were significantly elevated post infection. The transwell migration assay demonstrated that MHV-3-infected hepatocytes have the capacity to attract and recruit the splenic NK cells and T cells, and CXCL10 plays a key role in lymphocyte mobilization from the spleen. These results suggest that the CXCR3- associated chemokines (CXCL9 and CXCL10) may play animportant role in the recruitment of intrahepatic lymphocytes and subsequent necroinflammation and hepatic failure in MHV-3 infection.
文摘AIM:To assess and teach cultural competency skills at the fellowship training level through the use of objective structured clinical examinations(OSCEs).METHODS:We revised four scenarios to infuse a specific focus on cross-cultural care,and to render them appropriate for gastroenterology fellows.Three are discussed here:(1)Poor Health Literacy;(2)Disclosing/Apologizing for a Complication to a Patient Who Mistrusts the Healthcare System;and(3)Breaking Bad News to a Fatalistic Patient.A fourth case emphasizing shared decision-making will be described elsewhere.Four stations were completed by fellows and observed live by four faculty members,and the fellows’performance was assessed.RESULTS:Eleven fellows from four programs participated in the four OSCE.In the"Poor Health Literacy"case,18%(2/11)of participants recognized that the standardized patient(SP)had below-basic health literacy.None successfully evaluated the SP’s reading skills in a culturally-sensitive manner.In"Disclosing/Apologizing for a Complication",4/11(36%)personally apologized for the complication.1/11 recognized the SP’s mistrust of the medical system.With"Breaking Bad News",27%(3/11)explored the patient’s values to identify her fatalistic beliefs.CONCLUSION:OSCEs can be used to assess deficiencies in culturally-competent care at the fellowship level.OSCEs also afford fellowships the opportunity to inform future training curricula.
文摘The development of metal sulfide catalysts with remarkable activity toward efficient overall photocatalytic water splitting remains challenging owing to the dominant charge recombination and deficient catalytic active sites.Moreover,in the process of water oxidation catalysis,the inhibition of severe photocorrosion is an immense task,requiring effective photogenic hole-transfer kinetics.Herein,stratified Co-MnO_(2)@CdS/CoS hollow cubes with spatially separated catalytic sites were rationally designed and fabricated as highly efficient controllable catalysts for photocatalytic overall water splitting.The unique self-templated method,including a continuous anion/cation-exchange reaction,integrates a Co-doped oxidation co-catalyst(Co-MnO_(2))and a reduction co-catalyst(CoS)on the nanocubes with uniform interface contact and ultrathin two-dimensional(2D)nanometer sheets.We demonstrate that the stratified Co-MnO_(2)@CdS/CoS hollow cubes can provide an abundance of active sites for surface redox reactions and contribute to the separation and migration of the photoionization charge carriers.In particular,CoS nanoparticles dispersed on the walls of CdS hollow cubes were identified as reduction co-catalysts accelerating hydrogen generation,while Co-MnO_(2) nanosheets attached to the inner walls of the CdS hollow cube were oxidation co-catalysts,promoting oxygen evolution dynamics.Benefiting from the desirable structural and compositional advantages,optimized stratification of Co-MnO_(2)@CdS/CoS nanocubes provided a catalytic system devoid of precious metals,which exhibited a remarkable overall photocatalytic water-splitting rate(735.4(H_(2))and 361.1(O_(2))μmol h^(−1) g^(−1)),being among the highest values reported thus far for CdS-based catalysts.Moreover,an apparent quantum efficiency(AQE)of 1.32%was achieved for hydrogen evolution at 420 nm.This study emphasizes the importance of rational design on the structure and composition of photocatalysts for overall water splitting.
文摘To assess first-year gastroenterology fellows’ ability to address difficult interpersonal situations in the workplace using objective structured clinical examinations (OSCE).METHODSTwo OSCEs (“distracted care team” and “frazzled intern”) were created to assess response to disruptive behavior. In case 1, a fellow used a colonoscopy simulator while interacting with a standardized patient (SP), nurse, and attending physician all played by actors. The nurse and attending were instructed to display specific disruptive behavior and disregard the fellow unless requested to stop the disruptive behavior and focus on the patient and procedure. In case 2, the fellow was to calm an intern managing a patient with massive gastrointestinal bleeding. The objective in both scenarios was to assess the fellows’ ability to perform their duties while managing the disruptive behavior displayed by the actor. The SPs used checklists to rate fellows’ performances. The fellows completed a self-assessment survey.RESULTSTwelve fellows from four gastrointestinal fellowship training programs participated in the OSCE. In the “distracted care team” case, one-third of the fellows interrupted the conflict and refocused attention to the patient. Half of the fellows were able to display professionalism despite the heated discussion nearby. Fellows scored lowest in the interprofessionalism portion of post-OSCE surveys, measuring their ability to handle the conflict. In the “frazzled intern” case, 68% of fellows were able to establish a calm and professional relationship with the SP. Despite this success, only half of the fellows were successfully communicate a plan to the SP and only a third scored “well done” in a domain that focused on allowing the intern to think through the case with the fellow’s guidance.CONCLUSIONFellows must receive training on how to approach disruptive behavior. OSCEs are a tool that can assess fellow skills and set a culture for open discussion.
基金Sponsored by the National Natural Science Foundation of China(Grant No.51305108)Foundation for the Heilongjiang Province Ordinary University Youth Academic Backbone Support Program(Grant No.1254G025)China Postdoctoral Science Foundation(Grant No.2012M510982)
文摘In order to consider the influence of the continuous rotary motor electro-hydraulic servo system parameters change on its performance,the design method of backstepping adaptive controller is put forward.The mathematical model of electro-hydraulic servo system of continuous rotary motor is established,and the whole system is decomposed into several lower order subsystems,and the virtual control signal is designed for each subsystem from the final subsystem with motor angular displacement to the subsystem with system control input voltage. Based on Lyapunov method and the backstepping theory,an adaptive backstepping controller is designed with the changed parameters adaptive law. It is proved that the system reaches the global asymptotic stability,and the system tracking error asymptotically tends to zero. The simulation results show that the backstepping adaptive controller based on the adaptive law of the changed parameters can improve the performance of continuous rotary motor,and the proposed control strategy is feasible.
基金National Natural Science Foundation(No.81860836)Research Cultivation Fund of the First Affiliated Hospital of Hainan Medical College(No.HYFYPY201602)
文摘Objective:To evaluate the effect of individualized nutritional intervention therapy in patients with gestational diabetes mellitus(GDM).Methods:80 GDM inpatients admitted to the First Affiliated Hospital of Hainan Medical College from December 2015 to June 2018 were enrolled.According to the random number table method,the patients were divided into 4 groups,with 20 cases in each group.Group 1 used food exchange combined glycemic index method,group 2 used food exchange combined blood glucose load method,group 3 used glycemic index combined with blood glucose load method,group 4 combined glycemic index and blood glucose load method based on food exchange.After the intervention,the changes of blood glucose level,biochemical indexes and fetal growth and development indexes of the four groups were observed.Results:After nutritional intervention,the blood glucose levels of the four groups of patients decreased to varying degrees compared with before the intervention.The difference was statistically significant(P<0.05).In order to evaluate the advantages and disadvantages of the four methods,the blood glucose levels of the four groups of patients were further compared between groups:compared with group 1,group 2,group 4 and group 3,the differences were statistically significant(P<0.01 or 0.05).There was significant difference in blood glucose 2 hours after dinner between group 4 and group 1 and group 2(P<0.05).Comparing the biochemical indexes and fetal growth and development indexes of the four groups,the differences were not statistically significant(P>0.05).Conclusion:Individualized nutritional intervention therapy can significantly improve the blood glucose level of GDM patients,and at the same time meet the needs of the mother's own physiology and fetal growth and development.Among them,the nutrition intervention method that combines the glycemic index and the blood glucose load on the basis of the food exchange portion has a better effect on improving the blood glucose level of the patient.
基金support received from Yunnan Fundamental Research Projects(Grant No.202101BC070001-007)the Jiangsu Province Industry-University-Research Cooperation Project(No.BY2022832)the National Natural Science Foundation of China(No.52275339).
文摘The effects of Mn addition(0.005,0.01,0.03,0.05,and 0.07 wt.%)on microstructure,shear mechanical behavior,and interfacial thermal stabilities of SAC305 joints were investigated under isothermal aging temperatures of 170 C with different aging time(0,250,500,and 750 h).It is found that Mn addition can increase fracture energy of joints without decreasing the shear strength.And the microstructures have transformed from the eutectic net-like structure in SAC305 solder joints into the structures based onβ-Sn matrix with intermetallic compounds(IMCs)distributed.By doping 0.07 wt.%Mn,the Cu_(6)Sn_(5) growth along the SAC305/Cu interface during thermal aging can be inhibited to some extent.During isothermal aging at 170°C,the maximum shear force of solder joint decreases continuously with aging time increasing,while the fracture energy rises first and then decreases,reaching the maximum at 500 h compared by that with the microstructure homogenization.Cu_(3)Sn growth between Cu_(3)Sn_(5)/Cu interface has been retarded most at the aging time of 250 h with 0.07 wt.%Mn-doped joints.With the aging time prolonging,the inhibition effect of Mn on CusSn IMC layer becomes worse.The strengthening effect of Mn can be explained by precipitation strengthening,and its mechanical behavior can be predicted by particle strengthening model proposed by Orowan.
基金financially supported by the Natural National Science Foundation of China(22178084)the Natural Science Foundation for Distinguished Young Scholars of Hebei Province(No.B2015208010)+2 种基金Fundamental Research Funds for the Central Universitiesthe Foundation for Innovative Research Groups of the Natural Science Foundation of Hebei Province(No.B2021208005)National Key R&D Program of China(2022YFE0101800).
文摘Adjusting the interfacial transport efficiency of photogenerated electrons and the free energy of hydrogen adsorption through interface engineering is an effective means of improving the photocatalytic activity of semiconductor photocatalysts.Herein,hollow ZnS/NiS nanocages with ohmic contacts containing Zn vacancy(V_(Zn)-ZnS/NiS)are synthesized using ZIF-8 as templates.An internal electric field is constructed by Fermi level flattening to form ohmic contacts,which increase donor density and accelerate electron transport at the V_(Zn)-ZnS/NiS interface.The experimental and DFT results show that the tight interface and V_(Zn) can rearrange electrons,resulting in a higher charge density at the interface,and optimizing the Gibbs free energy of hydrogen adsorption.The optimal hydrogen production activity of V_(Zn)-ZnS/NiS is 10,636 mmol h^(-1) g^(-1),which is 31.9 times that of V_(Zn)-ZnS.This study provides an idea for constructing sulfide heterojunctions with ohmic contacts and defects to achieve efficient photocatalytic hydrogen production.
基金the National Natural Science Foundation of China(30470282).
文摘Chlorophyll fluorescence and antioxidative capability in detached leaves of the wild type Arabidopsis thaliana L. ecotype Landsberg erecta （Ler） and three mutants deficient in anthocyanins biosynthesis （tt3, tt4, and tt3tt4） were investigated during treatment with temperatures ranging 25-45 ℃. In comparison with the wild type, chlorophyll fluorescence parameters Fv/Fm, φps,, electron transport rate （ETR）, Fv/Fo and qP in three anthocyanin-deficient mutants showed a more rapidly decreasing rate when the temperature was over 35 ℃. Non-photochemical quenching （NPQ） in these mutants was almost completely lost at 44 ℃, whereas the content of heat stable protein dropped and the rate of the membrane leakage increased. Fo-temperature curves were obtained by monitoring Fo levels with gradually elevated temperatures from 22 ℃ to 72 ℃ at 0.5 ℃/min. The inflexion temperatures of Fo were 45.8 ℃ in Ler, 45.1℃ in tt3, 44.1℃ in tt4 and 42.3 ℃ in tt3tt4, respectively. The temperatures of maximal Fo in three mutants were 1.9-3.8℃ lower than the wild type plants. Meanwhile, three mutants had lower activities of superoxide dismutase （SOD） and ascorbate peroxidase （APX） and an inferior scavenging capability to DPPH （1.1-diphenyl-2-picrylhy.drazyl） radical under heat stress, and in particular tt3tt4 had the lowest antioxidative potential. The results of the diaminobenzidine-H2O2 histochemical staining showed that H2O2 was accumulated in the leaf vein and mesophyll cells of mutants under treatment at 40 ℃, and it was significantly presented in leaf cells of tt3tt4. The sensitivity of Arabidopsis anthocyanins-deficient mutants to high temperatures has revealed that anthocyanins in normal plants might provide protection from high temperature injury, by enhancing its antioxidative capability under high temperature stress.
基金supported by the National Science and Technology Project of China(No.2009ZX09311-004)the Natural Science Foundation of China(No.21072234).
文摘A new sesquiterpene lactone(1)and a new aromatic glycoside(2),together with three known compounds(3–5)were isolated from the stem bark of Illicium difengpi K.I.B et K.I.M.Their structures were determined by spectroscopic methods,including 1D and 2D NMR,HRESIMS,and chemical methods.The absolute configuration of the secondary alcohol in 1 was confirmed by Mosher’s method.Compound 2 exhibited significant anti-inflammatory activity with IC50 value of 6.72 mmol/L.
文摘Oral mucositis, a severe oral ulceration, is a common toxic effect of radioor chemoradio-therapy and a limiting factor to using the maximum dose of radiation for effective cancer treatment. Among cancer patients, at least 40% and up to 70%, of individuals treated with standard chemotherapy regimens or upper-body radiation, develop oral mucositis. To date, there is no FDA approved drug to treat oral mucositis in cancer patients. The key challenges for oral mucositis treatment are to repair and protect ulcerated oral mucosa without promoting cancer cell growth. Oral mucositis is the result of complex, multifaceted pathobiology, involving a series of signaling pathways and a chain of interactions between the epithelium and submucosa. Among those pathways and interactions, the activation of nuclear factor-kappa B （NF-KB） is critical to the inflamma- tion process of oral mucositis. We recently found that activation of TGFβ （transforming growth factor β） signaling is associated with the development of oral mucositis. Smad7, the negative regulator of TGFβ signaling, inhibits both NF-KB and TGFβ activation and thus plays a pivotal role in the prevention and treatment of oral mucositis by attenuating growth inhibition, apoptosis, and inflammation while promoting epithelial migration. The major objective of this review is to evaluate the known functions of Smad7, with a particular focus on its molecular mechanisms and its function in blocking multiple pathological processes in oral mucositis.
基金This work is supported in part by the National Natural Science Foundation of China(Nos.11901027 and 11871093)the Scientific Research Project of Beijing Municipal Education Commission(No.KM201910016001)+2 种基金the Pyramid Talent Training Project of BUCEA(JDYC20200327)the Bill&Melinda Gates Foundation(INV-005834)the Fundamental Research Funds for Beijing Universities(X20083).
文摘In this paper,a model of mumps transmission with quarantine measure is proposed and then the control reproduction number Rc of the model is obtained.This model admits a unique endemic equilibrium P*if and only if Rc>1,while the disease-free equilibrium P0 always exists.By using the technique of constructing Lyapunov functions and the generalized Lyapunov-LaSalle theorem,we first show that the equilibrium P0 is globally asymptotically stable(GAS)if Rc≤1;second,we prove that the equilibrium P*is GAS if Rc>1.Our results reveal that mumps can be eliminated from the community for Rc≤1 and it will be persistent for Rc>1,and quarantine measure can also effectively control the mumps transmission.
基金supported by the Natural Science Foundation of China(No.21132009)the National Science and Technology Project of China(No.2012ZX09301002-002)
文摘One new sesquiterpene compound, namely, illihenlactone A（1）, and one new prenylated C6–C3 compound, illihenryione H（2）, along with three known sesquiterpenes（3–5） were isolated from the stems of Illicium henryi. The structures of 1 and 2 were elucidated by spectroscopic evidence including NMR, HRESIMS and circular dichroism（CD）. Compound 2 exhibited a weak inhibitory ratio for bglucuronidase release induced by platelet-activating factor（PAF） in rat polymorphonuclear leukocytes（PMNs） in vitro.
基金This work was funded by grants from the Tongji Hospital for Pilot Scheme Project and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology(No.2017ZX10202201)。
文摘Background:Coronavirus disease 2019(COVID-19)is a serious and even lethal respiratory illness.The mortality of critically ill patients with COVID-19,especially short term mortality,is considerable.It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage,which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.Methods:In this retrospective observational study,we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12,2020.Demographic,clinical and laboratory data were collected and analyzed.A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95%confidence interval for assessing the risk factors for 30-day mortality.Results:The 30-day mortality was 11.8%(112 of 949 patients).Forty-nine point nine percent(474)patients had one or more comorbidities,with hypertension being the most common(359[37.8%]patients),followed by diabetes(169[17.8%]patients)and coronary heart disease(89[9.4%]patients).Age above 50 years,respiratory rate above 30 beats per minute,white blood cell count of more than 10×109/L,neutrophil count of more than 7×109/L,lymphocyte count of less than 0.8×109/L,platelet count of less than 100×109/L,lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19.A predictive CAPRL score was proposed integrating independent risk factors.The 30-day mortality were 0%(0 of 156),1.8%(8 of 434),12.9%(26 of 201),43.0%(55 of 128),and 76.7%(23 of 30)for patients with 0,1,2,3,≥4 points,respectively.Conclusions:We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19.It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.
