Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcut...Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freund’s adjuvant to the left hind sole. Forty Wistar rats were randomly divided into the model group, the low frequency (2 Hz) EA group, the high frequency EA (100 Hz) group and the body acupuncture group. After being modeled except the model group, the other three groups were treated with EA or body acupuncture in Yanglingquan points (bilateral) for 3 weeks, the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin, sectioning and staining with HE. Results: Obvious inflammatory cell infiltration, loosened synovial tissue, damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats.展开更多
Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applicat...Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications,the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems.Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation.Ac2–26,a 25-amino acid peptide derived from Annexin A(a pro-resolving mediator),has shown good efficacy in the treatment of inflammatory disorders.However,the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo.In this paper,we formed PEGylated lipid nanoparticles(LDNPs)by the co-assembly of l-ascorbyl palmitate(L-AP)and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn–glycero-3-phosphoethanolamine(DSPE-PEG 2 k)to encapsulate and deliver Ac2–26 peptides to the arthritic rats.They showed good stability and biocompatibility.After being intravenously administrated,Ac2–26 peptide-loaded PEGylated lipid nanoparticles(ADNPs)showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites.In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology.Therefore,the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.展开更多
BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understa...BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.展开更多
Rheumatoid arthritis is a chronic,systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate.Several drugs have been used for the treatment of rheumatoid arth...Rheumatoid arthritis is a chronic,systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate.Several drugs have been used for the treatment of rheumatoid arthritis,but their use is limited by suboptimal bioavailability,serious adverse effects,and nonnegligible first-pass effects.In contrast,transdermal drug delivery systems(TDDSs)can avoid these drawbacks and improve patient compliance,making them a promising option for the treatment of rheumatoid arthritis(RA).Of course,TDDSs also face unique challenges,as the physiological barrier of the skin makes drug delivery somewhat limited.To overcome this barrier and maximize drug delivery efficiency,TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology,and different generations of TDDSs have been derived,which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery.In this review,we summarize the different generations of transdermal drug delivery systems,the corresponding transdermal strategies,and their applications in the treatment of RA.展开更多
Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heteroge...Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.展开更多
文摘Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freund’s adjuvant to the left hind sole. Forty Wistar rats were randomly divided into the model group, the low frequency (2 Hz) EA group, the high frequency EA (100 Hz) group and the body acupuncture group. After being modeled except the model group, the other three groups were treated with EA or body acupuncture in Yanglingquan points (bilateral) for 3 weeks, the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin, sectioning and staining with HE. Results: Obvious inflammatory cell infiltration, loosened synovial tissue, damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats.
基金supported by the National Natural Science Foundation of China(No.82003661)。
文摘Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications,the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems.Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation.Ac2–26,a 25-amino acid peptide derived from Annexin A(a pro-resolving mediator),has shown good efficacy in the treatment of inflammatory disorders.However,the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo.In this paper,we formed PEGylated lipid nanoparticles(LDNPs)by the co-assembly of l-ascorbyl palmitate(L-AP)and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn–glycero-3-phosphoethanolamine(DSPE-PEG 2 k)to encapsulate and deliver Ac2–26 peptides to the arthritic rats.They showed good stability and biocompatibility.After being intravenously administrated,Ac2–26 peptide-loaded PEGylated lipid nanoparticles(ADNPs)showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites.In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology.Therefore,the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.
文摘BACKGROUND Hematopoietic stem cell(HSC)transplantation(HSCT)is being accepted as a standard of care in various inflammatory diseases.The treatment of rheumatoid arthritis(RA)has been closely evolving with the understanding of disease pathogenesis.With the rising resistance to the traditional disease-modifying antirheumatic drugs and targeted biological therapy,researchers are in pursuit of other methods for disease management.Since the ultimate goal of the ideal treatment of RA is to restore immune tolerance,HSCT attracts much attention considering its reparative,paracrine,and anti-inflammatory effects.However,a systematic review of studies on HSCT in RA is lacking.AIM To investigate the role of HSCT in the management of RA.METHODS A detailed search of PubMed,Scopus,EMBASE,Cochrane,and the Web of Science databases was made to identify the relevant articles till September 2020 following Cochrane and PRISMA guidelines.We extracted data including the number of patients,source of hematopoietic stem cells,their mobilization and conditioning regimens,results,and complications from the eligible studies.Results were dichotomized into success(ACR 50/70)and failure(ACR 20)based on the improvement from baseline characteristics.The methodological quality of the included studies was also assessed.Analysis was performed using OpenMeta[Analysis]software.RESULTS We included 17 studies(1 randomized controlled trial,11 prospective,and 5 retrospective studies)with 233 patients for analysis.HSCT provided a significantly beneficial overall improvement in the clinical grades of ACR criteria(Z=11.309,P<0.001).However,the remission was noted only till 24 mo and later on the significance of the result was lost(Z=1.737,P=0.082).A less than 1%treatmentrelated mortality was noted from the included studies.No major drug-related toxicities were noted in any of the included studies.All patients who underwent allogeneic HSCT received immunosuppression in the conditioning regimen to counteract the graft-vs-host reaction which made them vulnerable to infections.It is noted that the source of hematopoietic stem cells did not play a role in altering the functional outcome and both autologous(Z=9.972,P<0.001)and allogenic(Z=6.978,P<0.001)sources produced significant improvement in the outcome compared to the pre-operative state despite having a significant heterogeneity among the studies reporting them(I2=99.4,P<0.001).CONCLUSION Although the available literature is encouraging towards the use of HSCT in refractory cases with significant improvement from baseline till 2 years,the inclusion of HSCT into the standard of care of RA needs further exploration.
基金supported by the Scientific Research Project of Liaoning Province Education Department (2020LJC16),China。
文摘Rheumatoid arthritis is a chronic,systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate.Several drugs have been used for the treatment of rheumatoid arthritis,but their use is limited by suboptimal bioavailability,serious adverse effects,and nonnegligible first-pass effects.In contrast,transdermal drug delivery systems(TDDSs)can avoid these drawbacks and improve patient compliance,making them a promising option for the treatment of rheumatoid arthritis(RA).Of course,TDDSs also face unique challenges,as the physiological barrier of the skin makes drug delivery somewhat limited.To overcome this barrier and maximize drug delivery efficiency,TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology,and different generations of TDDSs have been derived,which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery.In this review,we summarize the different generations of transdermal drug delivery systems,the corresponding transdermal strategies,and their applications in the treatment of RA.
文摘Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.
