BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory ...BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory bowel disease(IBD)patients,are still controversial.AIM To determine the efficacy and safety of anti-TNF-αmonoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM interventions.METHODS As of July 2023,we searched for randomized controlled trials(RCTs)and observa-tional studies in PubMed,Embase,and the Cochrane Library to compare anti-TNF-αmonoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric therapy.Pairwise and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for surgery.RESULTS This systematic review and meta-analysis yielded 13 studies after exclusion,and the baseline indicators were balanced.We found a significant increase in the number of patients who achieved clinical remission in the ADA[odds ratio(OR)=1.416,95%confidence interval(CI):1.196-1.676]and RCT(OR=1.393,95%CI:1.182-1.641)subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive(OR=0.237,95%CI:0.101-0.558)and IFX+ADA(OR=0.137,95%CI:0.032-0.588)subgroups,and the overall risk of adverse events was reduced(OR=0.579,95%CI:0.391-0.858)according to the pairwise meta-analysis.Moreover,the network meta-analysis results suggested that patients with IBD treated with ADA(OR=1.39,95%CI:1.19-1.63)were more likely to undergo TDM,especially in comparison with patients with reactive TDM(OR=1.38,95%CI:1.07-1.77).CONCLUSION Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive TDM.We recommend proactive TDM in IBD patients who are treated with ADA.展开更多
Background： Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma.Trials comparing efficacy of standard melphalan and prednisone （MP） therapy with MP plus thali...Background： Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma.Trials comparing efficacy of standard melphalan and prednisone （MP） therapy with MP plus thalidomide （MPT） in transplant-ineligible or elderly patients with multiple myeloma （MM） have provided conflicting evidence.This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.Methods： Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology （1995-2014）, the American Society of Clinical Oncology （1995-2014）, and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings ＆quot;MM＆quot; and ＆quot;thalidomide＆quot;.Trials were assessed by two reviewers for eligibility.Meta-analysis was conducted using a fixed effects model.Sensitivity analysis was performed to test the robustness of the findings.Results： Overall, seven trials were identified, covering a total of 1821 subjects.The summary hazard ratio （thalidomide vs.control） was 0.82 （95% confidence interval [CI]： 0.72-0.94） for overall survival （OS）, and 0.65 （95% CI： 0.58-0.73） for progression-free survival, in favor of thalidomide treated group.The risk ratio of complete response with induction thalidomide was 3.48 （95% CI： 2.24-5.41）.A higher rate of Ⅲ/Ⅳ adverse events were observed in MPT arm compared with the MP arm.However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms （RR =1.47, 95% CI： 0.43-5.07, P =0.54）.Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms （RR =1.24, 95% CI： [0.95-1.63], P =0.120）.Conclusion： Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.展开更多
Objective: Parkinson’s disease(PD) is characterized by the loss of dopaminergic neurons in substantia nigra(SN). Our previous study demonstrated kukoamine A(KuA) to exhibit strong neuroprotective effects through anti...Objective: Parkinson’s disease(PD) is characterized by the loss of dopaminergic neurons in substantia nigra(SN). Our previous study demonstrated kukoamine A(KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP+-induced PD models in vivo and in vitro. It is necessary to evaluate the efficacy of the anti-PD effects under various models.Methods: In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex. Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD.Results: Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential(MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of a-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxininduced PD due to the apoptosis inhibition and iron homeostasis maintaining.Conclusion: KuA treatment might represent a neuroprotective treatment for PD.展开更多
Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer＇s disease, and Parkinson＇s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity ...Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer＇s disease, and Parkinson＇s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity plays an important role in neurodegenerative diseases. Glutamate toxicity seems to be mediated by excessive influx of Ca^（2＋） into neuronal cells through activation of N-methyl-D-aspartate（NMDA） receptor. To search for potential NMDA receptor inhibitors in traditional Chinese medicine. Methods A series of computer methods including drug-likeness evaluation, ADMET tests as well as molecular docking have been used. Results 1,5-O-dicaffeoyl-quinic acid was identified as NMDA receptor inhibitor by virtual screening. Its neuroprotective activity was further confirmed by in vitro test. 1,5-O-dicaffeoyl-quinic acid showed strong neuroprotection against NMDA-induced cell injury. Conclusion 1,5-O-Dicaffeoylquinic acid may be regarded as a potential NMDA receptor inhibitor for the prevention and treatment of neurodegenerative disorders.展开更多
Objective： The present study, for the first time, was designed to examine the antifibrosis effects of Shenge Yangfei Capsules（SGYF） on bleomycin-induced pulmonary injury and fibrosis in rats.Methods： Animals were ...Objective： The present study, for the first time, was designed to examine the antifibrosis effects of Shenge Yangfei Capsules（SGYF） on bleomycin-induced pulmonary injury and fibrosis in rats.Methods： Animals were divided into six groups randomly： saline control group, model group（bleomycin5 mg/kg）, and positive control group（Dexamethasone 5 mg/kg）, and SGYF（70, 420, and 850 mg/kg/d, ig）group. Effects of SGYF on body weight and lung index were evaluated. For histological evaluation of lungs injury and fibrosis, lung specimens were stained with hematoxylin and eosin（HE） and Masson trichrome.Body weight and lung index from various groups were measured, and the concentrations of monoamine（MAO） and transforming growth factor-β1（TGF-β1） were also detected in lung homogenates.Results： SGYF attenuated the bleomycin-induced weight loss and the lung index. Histologica levidence showed the ability of SGYF to decrease bleomycin-induced lung fibrosis and consolidation. SGYF reduced MAO and TGF-β1 activity in lung tissues.Conclusions： These findings suggest that SGYF may be a promising candidate to prevent bleomycininduced lung damage or other interstitial lesions.展开更多
基金Supported by National College Students Innovation and Entrepreneurship Training Program of Shenyang Pharmaceutical University,No.202210163003.
文摘BACKGROUND The efficacy and safety of anti-tumor necrosis factor-α(TNF-α)monoclonal antibody therapy[adalimumab(ADA)and infliximab(IFX)]with therapeutic drug monitoring(TDM),which has been proposed for inflammatory bowel disease(IBD)patients,are still controversial.AIM To determine the efficacy and safety of anti-TNF-αmonoclonal antibody therapy with proactive TDM in patients with IBD and to determine which subtype of IBD patients is most suitable for proactive TDM interventions.METHODS As of July 2023,we searched for randomized controlled trials(RCTs)and observa-tional studies in PubMed,Embase,and the Cochrane Library to compare anti-TNF-αmonoclonal antibody therapy with proactive TDM with therapy with reactive TDM or empiric therapy.Pairwise and network meta-analyses were used to determine the IBD patient subtype that achieved clinical remission and to determine the need for surgery.RESULTS This systematic review and meta-analysis yielded 13 studies after exclusion,and the baseline indicators were balanced.We found a significant increase in the number of patients who achieved clinical remission in the ADA[odds ratio(OR)=1.416,95%confidence interval(CI):1.196-1.676]and RCT(OR=1.393,95%CI:1.182-1.641)subgroups and a significant decrease in the number of patients who needed surgery in the proactive vs reactive(OR=0.237,95%CI:0.101-0.558)and IFX+ADA(OR=0.137,95%CI:0.032-0.588)subgroups,and the overall risk of adverse events was reduced(OR=0.579,95%CI:0.391-0.858)according to the pairwise meta-analysis.Moreover,the network meta-analysis results suggested that patients with IBD treated with ADA(OR=1.39,95%CI:1.19-1.63)were more likely to undergo TDM,especially in comparison with patients with reactive TDM(OR=1.38,95%CI:1.07-1.77).CONCLUSION Proactive TDM is more suitable for IBD patients treated with ADA and has obvious advantages over reactive TDM.We recommend proactive TDM in IBD patients who are treated with ADA.
文摘Background： Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma.Trials comparing efficacy of standard melphalan and prednisone （MP） therapy with MP plus thalidomide （MPT） in transplant-ineligible or elderly patients with multiple myeloma （MM） have provided conflicting evidence.This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma.Methods： Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology （1995-2014）, the American Society of Clinical Oncology （1995-2014）, and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings ＆quot;MM＆quot; and ＆quot;thalidomide＆quot;.Trials were assessed by two reviewers for eligibility.Meta-analysis was conducted using a fixed effects model.Sensitivity analysis was performed to test the robustness of the findings.Results： Overall, seven trials were identified, covering a total of 1821 subjects.The summary hazard ratio （thalidomide vs.control） was 0.82 （95% confidence interval [CI]： 0.72-0.94） for overall survival （OS）, and 0.65 （95% CI： 0.58-0.73） for progression-free survival, in favor of thalidomide treated group.The risk ratio of complete response with induction thalidomide was 3.48 （95% CI： 2.24-5.41）.A higher rate of Ⅲ/Ⅳ adverse events were observed in MPT arm compared with the MP arm.However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms （RR =1.47, 95% CI： 0.43-5.07, P =0.54）.Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms （RR =1.24, 95% CI： [0.95-1.63], P =0.120）.Conclusion： Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.
基金supported by the Natural Science Foundation of Liaoning Province,China.(Project number:20170540945)。
文摘Objective: Parkinson’s disease(PD) is characterized by the loss of dopaminergic neurons in substantia nigra(SN). Our previous study demonstrated kukoamine A(KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP+-induced PD models in vivo and in vitro. It is necessary to evaluate the efficacy of the anti-PD effects under various models.Methods: In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex. Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD.Results: Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential(MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of a-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxininduced PD due to the apoptosis inhibition and iron homeostasis maintaining.Conclusion: KuA treatment might represent a neuroprotective treatment for PD.
基金Key National Science and Technology Specific Project of China(2014ZX09J14101-05C)
文摘Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer＇s disease, and Parkinson＇s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity plays an important role in neurodegenerative diseases. Glutamate toxicity seems to be mediated by excessive influx of Ca^（2＋） into neuronal cells through activation of N-methyl-D-aspartate（NMDA） receptor. To search for potential NMDA receptor inhibitors in traditional Chinese medicine. Methods A series of computer methods including drug-likeness evaluation, ADMET tests as well as molecular docking have been used. Results 1,5-O-dicaffeoyl-quinic acid was identified as NMDA receptor inhibitor by virtual screening. Its neuroprotective activity was further confirmed by in vitro test. 1,5-O-dicaffeoyl-quinic acid showed strong neuroprotection against NMDA-induced cell injury. Conclusion 1,5-O-Dicaffeoylquinic acid may be regarded as a potential NMDA receptor inhibitor for the prevention and treatment of neurodegenerative disorders.
基金financially supported by Guanghua Fund(No.413FZ08)
文摘Objective： The present study, for the first time, was designed to examine the antifibrosis effects of Shenge Yangfei Capsules（SGYF） on bleomycin-induced pulmonary injury and fibrosis in rats.Methods： Animals were divided into six groups randomly： saline control group, model group（bleomycin5 mg/kg）, and positive control group（Dexamethasone 5 mg/kg）, and SGYF（70, 420, and 850 mg/kg/d, ig）group. Effects of SGYF on body weight and lung index were evaluated. For histological evaluation of lungs injury and fibrosis, lung specimens were stained with hematoxylin and eosin（HE） and Masson trichrome.Body weight and lung index from various groups were measured, and the concentrations of monoamine（MAO） and transforming growth factor-β1（TGF-β1） were also detected in lung homogenates.Results： SGYF attenuated the bleomycin-induced weight loss and the lung index. Histologica levidence showed the ability of SGYF to decrease bleomycin-induced lung fibrosis and consolidation. SGYF reduced MAO and TGF-β1 activity in lung tissues.Conclusions： These findings suggest that SGYF may be a promising candidate to prevent bleomycininduced lung damage or other interstitial lesions.
