Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the ...Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the large penetration depth in tissue.However,the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application.Due to the long lifespan and transmission distance of therapeutic gas molecules,we design a multi-functional gas generator that combines aPDT as well as O_(2) and CO gas release function,which can solve the problem of hypoxia(O_(2))in PDT and the problem of inflammation regulation(CO)in the distal part of peri‑implant inflammation under near-infrared(NIR)irradiation.In the composite nanoplatform that spin-coated on the surface of titanium implants,up-conversion nanoparticles(UCNPs)were involved in converting the NIR to visible,which further excites the partially oxidized stannic sulfide(SnS_(2)),realizing the therapeutic gas release.Indocyanine green(ICG)was further integrated to enhance the aPDT performance(Ti-U@SnS_(2)/I).Therefore,reactive oxygen species(ROS),CO,and O_(2) can be controllably administered via a composite nano-platform mediated by a single NIR light(808 nm).This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions,such as relieving the anoxic microenvironment and reaching deep infection sites,providing a viable antibiotic-free technique to combat peri‑implantitis.展开更多
Dear Editor,Previous studies have proved that regulatory T cell(Treg)insufficiency contributed to the development of autoimmune conditions including systemic lupus erythematosus(SLE).Conventional immunosuppressive tre...Dear Editor,Previous studies have proved that regulatory T cell(Treg)insufficiency contributed to the development of autoimmune conditions including systemic lupus erythematosus(SLE).Conventional immunosuppressive treatment was reported to downregulate beneficial Tregs together with pathogenic effector immune cells,which may impede a rapid achievement of optimal therapeutic effects.展开更多
Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a ther...Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.展开更多
Objective:A retrospective study was performed to compare the difference in platelet count(PLT),prothrombin time(PT),international normalized ratio(INR),and activated partial thromboplastin time(APTT),between cirrhotic...Objective:A retrospective study was performed to compare the difference in platelet count(PLT),prothrombin time(PT),international normalized ratio(INR),and activated partial thromboplastin time(APTT),between cirrhotic patients with and without acute upper gastrointestinal bleeding(AUGIB)or acute oesophageal variceal bleeding(AEVB).Methods:Between January 2012 and June 2014,a total of 1734 cirrhotic patients were enrolled and were classified into‘AUGIB’(n=497)and‘no AUGIB’(n=1237)groups according to their disease history.They were further divided into‘AEVB’(n=297)and‘no AEVB’(n=1259)groups according to the endoscopic findings.Additionally,178 patients with AUGIB were not assigned to either the‘AEVB’or‘no AEVB’groups due to the absence of any endoscopic findings.Results:Compared with the‘no AUGIB’group,the‘AUGIB’group had similar PLT(99.99689.90 vs.101.47683.03;P=0.734)and APTT(42.96±15.20 vs.43.77611.01;P=0.219),but significantly higher PT(17.30±5.62 vs.16.03±64.68;P<0.001)and INR(1.45±0.69 vs.1.316±0.59;P<0.001).A lower PT was independently associated with the absence of AUGIB(OR=0.968;95%CI:0.942–0.994).Compared with the‘no AEVB’group,the‘AEVB’group had significantly lower PLT(86.87662.14 vs.101.74683.62;P=0.004)and APTT(40.98±67.9 vs.43.72±10.97;P<0.001),but similar PT(16.53±3.71 vs.16.04±4.68;P=0.088)and INR(1.35±0.41 vs.1.31±0.59;P=0.225).A higher PLT was independently associated with the absence of AEVB(OR=1.004;95%CI:1.002–1.006;P=0.001).Conclusions:PLT was associated with the occurrence of portal hypertension-related bleeding in liver cirrhosis.展开更多
Description logics （DLs） are widely employed in recent semantic web application systems. However, classical description logics are limited when dealing with imprecise concepts and roles, thus providing the motivatio...Description logics （DLs） are widely employed in recent semantic web application systems. However, classical description logics are limited when dealing with imprecise concepts and roles, thus providing the motivation for this work. In this paper, we present a type-2 fuzzy attributive concept language with complements （ALC） and provide its knowledge representation and reasoning algorithms. We also propose type-2 fuzzy web ontology language （OWL） to build a fuzzy ontology based on type- 2 fuzzy ALC and analyze the soundness, completeness, and complexity of the reasoning algorithms. Compared to type-1 fuzzy ALC, type-2 fuzzy ALC can describe imprecise knowledge more meticulously by using the membership degree interval. We implement a semantic search engine based on type-2 fuzzy ALC and carry out experiments on real data to test its performance. The results show that the type-2 fuzzy ALC can improve the precision and increase the number of relevant hits for imprecise information searches.展开更多
There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune diseases.Here we investigated the inhibitory effect and possible mechanism of an altered influ...There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune diseases.Here we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin(HA)-derived peptide in collagen-induced arthritis(CIA).CIA was induced in DBA/1 mice by immunisation with type II collagen(CII).Altered HA308-317,wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis onset.Clinical and histological scores were assessed,and cytokine levels in the serum or supernatants from splenocytes were determined.The percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in vitro.Our results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated CIA.The therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon(IFN)-c,interleukin(IL)-6,monocyte chemoattractant protein(MCP)-1,anti-CII IgG,IgG1 and IgG2a antibodies,and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 peptide.The percentage of Th2(CD41IL-41)cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1(T helper 1;CD41INF-c1)cells both in vivo and in vitro.These findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis(RA)treatment.展开更多
Background:A specific feature of the autoimmune response in rheumatoid arthritis(RA)is the presence of anti-citrullinated protein antibodies(ACPAs)in patient sera.These antibodies can appear several years before disea...Background:A specific feature of the autoimmune response in rheumatoid arthritis(RA)is the presence of anti-citrullinated protein antibodies(ACPAs)in patient sera.These antibodies can appear several years before disease onset and are involved in the development of RA.Objective:We performed proteomic analysis by mass spectroscopy to identify novel citrullinated antigens and autoantibodies in RA patients.Methods:Polypeptides isolated from the sera of RA patients were identified by Orbitrap high-precision mass spectrometry and then citrulline-containing proteins were selected.The levels of ACPAs against these newly identified citrullinated autoantigens in sera of 100 RA patients and 50 healthy controls were determined by enzyme-linked immunosorbent assays.Results:A total of 135 proteins were identified in RA patients and the protein profile included 11 citrulline-containing antigens.Three of the 11 citrullinated proteins had been reported in previous studies.ACPAs against the novel citrullinated epitopes from these proteins were increased in sera from the RA patients compared with those from healthy controls.Autoantibodies against one of the citrullinated antigens,lipopolysaccharide-binding protein(LBP),was significantly increased in RA patients and associated with disease activities.The titer of anti-citrullinated LBP antibodies(anti-cLBP)was closely related to the infection incidence in RA patients.Conclusion:Serum protein analysis by high-precision proteomic technology is a feasible method to identify novel citrullinated epitopes in RA patients.Anti-cLBP antibodies are associated with disease severity and infection in RA patients.展开更多
基金the National Natural Science Foundation of China(Nos.82170998,82201102,62205122)the Postdoctoral Science Foundation Project of China(No.2022M721316)+4 种基金the General program of the Natural Science Foundation of Jilin Province(Nos.YDZJ202201ZYTS017,20220203145SF,20210203087SF,YDZJ202201ZYTS274,YDZJ202201ZYTS080)Hygiene and Health Appropriate Technology Promotion Project of Jilin Province(No.2020S014)the Science and Technology Project of Jilin Province Financial Department(Nos.jcsz202189321,jcsz2021893-15,Zkjc D105181350043103358)Science and Technology Project of Jilin Province Education Department(No.JJKH20221098KJ)the Health Department Research Projects of Jilin Province(No.2022JC076)for financial support.
文摘Antimicrobial photodynamic therapy(aPDT)has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis,especially the aPDT triggered by near-infrared(NIR)light due to the large penetration depth in tissue.However,the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application.Due to the long lifespan and transmission distance of therapeutic gas molecules,we design a multi-functional gas generator that combines aPDT as well as O_(2) and CO gas release function,which can solve the problem of hypoxia(O_(2))in PDT and the problem of inflammation regulation(CO)in the distal part of peri‑implant inflammation under near-infrared(NIR)irradiation.In the composite nanoplatform that spin-coated on the surface of titanium implants,up-conversion nanoparticles(UCNPs)were involved in converting the NIR to visible,which further excites the partially oxidized stannic sulfide(SnS_(2)),realizing the therapeutic gas release.Indocyanine green(ICG)was further integrated to enhance the aPDT performance(Ti-U@SnS_(2)/I).Therefore,reactive oxygen species(ROS),CO,and O_(2) can be controllably administered via a composite nano-platform mediated by a single NIR light(808 nm).This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions,such as relieving the anoxic microenvironment and reaching deep infection sites,providing a viable antibiotic-free technique to combat peri‑implantitis.
基金supported by the Natural Science Foundation of China (81971520,32141004,82171775)Project (RDGS2022-05) supported by Peking University People's Hospital Scientific Research Development FundsBeijing Children's Hospital Young Investigator Program.
文摘Dear Editor,Previous studies have proved that regulatory T cell(Treg)insufficiency contributed to the development of autoimmune conditions including systemic lupus erythematosus(SLE).Conventional immunosuppressive treatment was reported to downregulate beneficial Tregs together with pathogenic effector immune cells,which may impede a rapid achievement of optimal therapeutic effects.
基金National Natural Science Foundation of China(U1903210,31530020,81701598,31570880,81471601,81801617)Beijing SciTech Program(Z171100000417007,Z191100006619114)Macao Science and Technology Fund(0094/2018/A3).
文摘Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.
基金This study was partially supported by the grant from the National Natural Science Foundation of China(no.81500474)Natural Science Foundation of Liaoning Province(no.2015020409).
文摘Objective:A retrospective study was performed to compare the difference in platelet count(PLT),prothrombin time(PT),international normalized ratio(INR),and activated partial thromboplastin time(APTT),between cirrhotic patients with and without acute upper gastrointestinal bleeding(AUGIB)or acute oesophageal variceal bleeding(AEVB).Methods:Between January 2012 and June 2014,a total of 1734 cirrhotic patients were enrolled and were classified into‘AUGIB’(n=497)and‘no AUGIB’(n=1237)groups according to their disease history.They were further divided into‘AEVB’(n=297)and‘no AEVB’(n=1259)groups according to the endoscopic findings.Additionally,178 patients with AUGIB were not assigned to either the‘AEVB’or‘no AEVB’groups due to the absence of any endoscopic findings.Results:Compared with the‘no AUGIB’group,the‘AUGIB’group had similar PLT(99.99689.90 vs.101.47683.03;P=0.734)and APTT(42.96±15.20 vs.43.77611.01;P=0.219),but significantly higher PT(17.30±5.62 vs.16.03±64.68;P<0.001)and INR(1.45±0.69 vs.1.316±0.59;P<0.001).A lower PT was independently associated with the absence of AUGIB(OR=0.968;95%CI:0.942–0.994).Compared with the‘no AEVB’group,the‘AEVB’group had significantly lower PLT(86.87662.14 vs.101.74683.62;P=0.004)and APTT(40.98±67.9 vs.43.72±10.97;P<0.001),but similar PT(16.53±3.71 vs.16.04±4.68;P=0.088)and INR(1.35±0.41 vs.1.31±0.59;P=0.225).A higher PLT was independently associated with the absence of AEVB(OR=1.004;95%CI:1.002–1.006;P=0.001).Conclusions:PLT was associated with the occurrence of portal hypertension-related bleeding in liver cirrhosis.
基金Acknowledgements This work was supported by the National Natural Science Foundation of China （Grant Nos. 60873225, 60873083, and 70771043）, the National High Technology Research and Development Program of China （2007AA01Z403）, the Natural Science Foundation of Hubei Province （2009CDB298）, the Natural Science Foundation of Hubei Province for Distinguished Young Scholars （2008CDB351）, the Wuhan Youth Science and Technology Chenguang Program （200950431171）, the Open Foundation of State Key Laboratory of Software Engineering （SKLSE20080718）, the Innovation Fund of Huazhong University of Science and Technology （2010MS068, Q2009021）.
文摘Description logics （DLs） are widely employed in recent semantic web application systems. However, classical description logics are limited when dealing with imprecise concepts and roles, thus providing the motivation for this work. In this paper, we present a type-2 fuzzy attributive concept language with complements （ALC） and provide its knowledge representation and reasoning algorithms. We also propose type-2 fuzzy web ontology language （OWL） to build a fuzzy ontology based on type- 2 fuzzy ALC and analyze the soundness, completeness, and complexity of the reasoning algorithms. Compared to type-1 fuzzy ALC, type-2 fuzzy ALC can describe imprecise knowledge more meticulously by using the membership degree interval. We implement a semantic search engine based on type-2 fuzzy ALC and carry out experiments on real data to test its performance. The results show that the type-2 fuzzy ALC can improve the precision and increase the number of relevant hits for imprecise information searches.
基金grants from the National Major Scientific and Technological Specialized Project(2009ZX09103-746)National Program on Key Basic Research Project(2010CB529100)National Natural Science Foundation of China(30700751).
文摘There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune diseases.Here we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin(HA)-derived peptide in collagen-induced arthritis(CIA).CIA was induced in DBA/1 mice by immunisation with type II collagen(CII).Altered HA308-317,wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis onset.Clinical and histological scores were assessed,and cytokine levels in the serum or supernatants from splenocytes were determined.The percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in vitro.Our results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated CIA.The therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon(IFN)-c,interleukin(IL)-6,monocyte chemoattractant protein(MCP)-1,anti-CII IgG,IgG1 and IgG2a antibodies,and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 peptide.The percentage of Th2(CD41IL-41)cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1(T helper 1;CD41INF-c1)cells both in vivo and in vitro.These findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis(RA)treatment.
基金Peking University People's Hospital Research and Development Funds,Grant/Award Number:RDX2019-03National Natural Science Foundation of China,Grant/Award Numbers:81971520,U1903210,81671602Beijing Municipal Science and Technology Project,Grant/Award Numbers:Z191100006619112,Z191100006619110。
文摘Background:A specific feature of the autoimmune response in rheumatoid arthritis(RA)is the presence of anti-citrullinated protein antibodies(ACPAs)in patient sera.These antibodies can appear several years before disease onset and are involved in the development of RA.Objective:We performed proteomic analysis by mass spectroscopy to identify novel citrullinated antigens and autoantibodies in RA patients.Methods:Polypeptides isolated from the sera of RA patients were identified by Orbitrap high-precision mass spectrometry and then citrulline-containing proteins were selected.The levels of ACPAs against these newly identified citrullinated autoantigens in sera of 100 RA patients and 50 healthy controls were determined by enzyme-linked immunosorbent assays.Results:A total of 135 proteins were identified in RA patients and the protein profile included 11 citrulline-containing antigens.Three of the 11 citrullinated proteins had been reported in previous studies.ACPAs against the novel citrullinated epitopes from these proteins were increased in sera from the RA patients compared with those from healthy controls.Autoantibodies against one of the citrullinated antigens,lipopolysaccharide-binding protein(LBP),was significantly increased in RA patients and associated with disease activities.The titer of anti-citrullinated LBP antibodies(anti-cLBP)was closely related to the infection incidence in RA patients.Conclusion:Serum protein analysis by high-precision proteomic technology is a feasible method to identify novel citrullinated epitopes in RA patients.Anti-cLBP antibodies are associated with disease severity and infection in RA patients.
