BACKGROUND Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis(SAP)-related acute lung injury(ALI).Inhibition of ...BACKGROUND Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis(SAP)-related acute lung injury(ALI).Inhibition of p38 by SB203580 blocked the inflammatory responses in SAP-ALI.However,the precise mechanism associated with p38 is unclear,particularly in pulmonary microvascular endothelial cell(PMVEC)injury.AIM To determine its role in the tumor necrosis factor-alpha(TNF-α)-induced inflammation and apoptosis of PMVECs in vitro.We then conducted in vivo experiments to confirm the effect of SB203580-mediated p38 inhibition on SAP-ALI.METHODS In vitro,PMVEC were transfected with mitogen-activated protein kinase kinase 6(Glu),which constitutively activates p38,and then stimulated with TNF-α.Flow cytometry and western blotting were performed to detect the cell apoptosis and inflammatory cytokine levels,respectively.In vivo,SAP-ALI was induced by 5%sodium taurocholate and three different doses of SB203580(2.5,5.0 or 10.0 mg/kg)were intraperitoneally injected prior to SAP induction.SAP-ALI was assessed by performing pulmonary histopathology assays,measuring myeloperoxidase activity,conducting arterial blood gas analyses and measuring TNF-α,interleukin(IL)-1βand IL-6 levels.Lung microvascular permeability was measured by determining bronchoalveolar lavage fluid protein concentration,Evans blue pulmonary cells was confirmed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis and examining the Bcl2,Bax,Bim and cle-caspase3 levels.The proteins levels of P-p38,NFκB,IκB,P-signal transducer and activator of transcription-3,nuclear factor erythroid 2-related factor 2,HO-1 and Myd88 were detected in the lungs to further evaluate the potential mechanism underlying the protective effect of SB203580.RESULTS In vitro,mitogen-activated protein kinase(Glu)transfection resulted in higher apoptotic rates and cytokine(IL-1βand IL-6)levels in TNF-α-treated PMVECs.In vivo,SB2035080 attenuated lung histopathological injury,decreased inflammatory activity(TNF-α,IL-1β,IL-6 and myeloperoxidase)and preserved pulmonary function.Furthermore,SB203580 significantly reversed changes in the bronchoalveolar lavage fluid protein concentration,Evans blue accumulation,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell numbers,apoptosis-related proteins(cle-caspase3,Bim and Bax)and endothelial microstructure.Moreover,SB203580 significantly reduced the pulmonary P-p38,NFκB,P-signal transducer and activator of transcription-3 and Myd88 levels but increased the IκB and HO-1 levels.CONCLUSION p38 inhibition may protect against SAP-ALI by alleviating inflammation and the apoptotic death of PMVECs.展开更多
Objective:To evaluate the effectiveness and safety of fire needling for herpes zoster from randomized clinical trials (RCTs).Methods:We searched Cochrane Central Register of Controlled Trials,Pubmed,Sino-Med,CNKI,VIP,...Objective:To evaluate the effectiveness and safety of fire needling for herpes zoster from randomized clinical trials (RCTs).Methods:We searched Cochrane Central Register of Controlled Trials,Pubmed,Sino-Med,CNKI,VIP,WanFang databases,and conference proceedings to November,2017.RCTs were eligible if they tested fire needling for treating herpes zoster more than 3 times.Two authors screened all references,assessed the risk of bias,extracted data,independently,and analyzed data using Trial Sequential Analysis (TSA).Treatment effects were presented as risk ratio (RR)for binary data and standardized mean difference (SMD) for continuous data with 95% confidence interval (CI).Results:We included 27 RCTs with a total of 1933 participants.Only one RCT had low risk of bias,and the others were of high or moderate risk of bias.For total effectiveness rate (proportion of total number of people who were cured or significant symptom improved),there was no significant difference between Western medicine (acyclovir,valacyclovir,adenosine cobalamin) and fire needling (risk ratio 1.05,95% CI 0.98 to 1.12;n =5).For pain relief (VAS scale):fire needling used alone showed lower scores than Western medicine (SMD-1.37,95% CI-1.77 to-0.97;n =2) or external medicine (diclofenac) (SMD-2.23,95% CI-2.81 to-1.64;n =1).Combination of fire needling and Western medicine was better than Western medicine alone in relieving pain (VAS scale) (SMD-2.19,95% CI-3.40 to-0.97,I2 =94%;n =4).Patients receiving fire needling had lower incidence of neuralgia than those receiving Western medicine (3.3% vs 26.7%,RR 0.09,95% Cl 0.01 to 0.82;n =1) at follow up for 30 days.No serious adverse events such as infection were reported.Conclusion:Fire needling appears to offer relief for alleviating pain in herpes zoster.As the sample size of included trials was small and the quality of studies was generally low,rigorous clinical trials with robust reporting and appropriate outcome measures are still needed.展开更多
The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the c...The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development.The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses,influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.展开更多
Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created...Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.展开更多
A Large-Scale Heterogeneous Network(LS-HetNet)integrates different networks into one uniform network system to provide seamless one-world network coverage.In LS-HetNet,various devices use different technologies to acc...A Large-Scale Heterogeneous Network(LS-HetNet)integrates different networks into one uniform network system to provide seamless one-world network coverage.In LS-HetNet,various devices use different technologies to access heterogeneous networks and generate a large amount of data.For dealing with a large number of access requirements,these data are usually stored in the HetNet Domain Management Server(HDMS)of the current domain,and HDMS uses a centralized Authentication/Authorization/Auditing(AAA)scheme to protect the data.However,this centralized method easily causes the data to be modified or disclosed.To address this issue,we propose a blockchain-empowered AAA scheme for accessing data of LS-HetNet.Firstly,the account address of the blockchain is used as the identity authentication,and the access control permission of data is redesigned and stored on the blockchain,then processes of AAA are redefined.Finally,the experimental model on Ethereum private chain is built,and the results show that the scheme is not only secure but also decentral,without tampering and trustworthiness.展开更多
Objective:With using natural language processing (NLP) technology to analyze and process the text of "Treatise on Febrile Diseases (TFDs)"for the sake of finding important information, this paper attempts to...Objective:With using natural language processing (NLP) technology to analyze and process the text of "Treatise on Febrile Diseases (TFDs)"for the sake of finding important information, this paper attempts to apply NLP in the field of text mining of traditional Chinese medicine (TCM)literature. Materials and Methods:Based on the Python language, the experiment invoked the NLP toolkit such as Jieba, nltk, gensim,and sklearn library, and combined with Excel and Word software. The text of "TFDs" was sequentially cleaned, segmented, and moved the stopped words, and then implementing word frequency statistics and analysis, keyword extraction, named entity recognition (NER) and other operations, finally calculating text similarity. Results:Jieba can accurately identify the herbal name in "TFDs." Word frequency statistics based on the word segmentation found that "warm therapy" is an important treatment of "TFDs." Guizhi decoction is the main prescription,and five core decoctions are identified. Keyword extraction based on the term "frequency-inverse document frequency" algorithm is ideal.The accuracy of NER in "TFDs" is about 86%;latent semantic indexing model calculating the similarity,"Understanding of Synopsis of Golden Chamber (SGC)" is much more similar with "SGC" than with "TFDs." The results meet expectation. Conclusions:It lays a research foundation for applying NLP to the field of text mining of unstructured TCM literature. With the combination of deep learning technology,NLP as an important branch of artificial intelligence will have broader application prospective in the field of text mining in TCM literature and construction of TCM knowledge graph as well as TCM knowledge services.展开更多
Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies(GWAS), these...Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies(GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body's immune system and is likely related to genetic mutations in systemic autoimmune diseases.Next-generation sequencing(NGS) technology, with high-throughput capacity and accuracy,provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.展开更多
基金National Natural Science Foundation of China,No.81873107,No.82004154 and No.81573766Science and Technology Planning Program of Sichuan,No.2019YFS0259.
文摘BACKGROUND Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis(SAP)-related acute lung injury(ALI).Inhibition of p38 by SB203580 blocked the inflammatory responses in SAP-ALI.However,the precise mechanism associated with p38 is unclear,particularly in pulmonary microvascular endothelial cell(PMVEC)injury.AIM To determine its role in the tumor necrosis factor-alpha(TNF-α)-induced inflammation and apoptosis of PMVECs in vitro.We then conducted in vivo experiments to confirm the effect of SB203580-mediated p38 inhibition on SAP-ALI.METHODS In vitro,PMVEC were transfected with mitogen-activated protein kinase kinase 6(Glu),which constitutively activates p38,and then stimulated with TNF-α.Flow cytometry and western blotting were performed to detect the cell apoptosis and inflammatory cytokine levels,respectively.In vivo,SAP-ALI was induced by 5%sodium taurocholate and three different doses of SB203580(2.5,5.0 or 10.0 mg/kg)were intraperitoneally injected prior to SAP induction.SAP-ALI was assessed by performing pulmonary histopathology assays,measuring myeloperoxidase activity,conducting arterial blood gas analyses and measuring TNF-α,interleukin(IL)-1βand IL-6 levels.Lung microvascular permeability was measured by determining bronchoalveolar lavage fluid protein concentration,Evans blue pulmonary cells was confirmed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis and examining the Bcl2,Bax,Bim and cle-caspase3 levels.The proteins levels of P-p38,NFκB,IκB,P-signal transducer and activator of transcription-3,nuclear factor erythroid 2-related factor 2,HO-1 and Myd88 were detected in the lungs to further evaluate the potential mechanism underlying the protective effect of SB203580.RESULTS In vitro,mitogen-activated protein kinase(Glu)transfection resulted in higher apoptotic rates and cytokine(IL-1βand IL-6)levels in TNF-α-treated PMVECs.In vivo,SB2035080 attenuated lung histopathological injury,decreased inflammatory activity(TNF-α,IL-1β,IL-6 and myeloperoxidase)and preserved pulmonary function.Furthermore,SB203580 significantly reversed changes in the bronchoalveolar lavage fluid protein concentration,Evans blue accumulation,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell numbers,apoptosis-related proteins(cle-caspase3,Bim and Bax)and endothelial microstructure.Moreover,SB203580 significantly reduced the pulmonary P-p38,NFκB,P-signal transducer and activator of transcription-3 and Myd88 levels but increased the IκB and HO-1 levels.CONCLUSION p38 inhibition may protect against SAP-ALI by alleviating inflammation and the apoptotic death of PMVECs.
文摘Objective:To evaluate the effectiveness and safety of fire needling for herpes zoster from randomized clinical trials (RCTs).Methods:We searched Cochrane Central Register of Controlled Trials,Pubmed,Sino-Med,CNKI,VIP,WanFang databases,and conference proceedings to November,2017.RCTs were eligible if they tested fire needling for treating herpes zoster more than 3 times.Two authors screened all references,assessed the risk of bias,extracted data,independently,and analyzed data using Trial Sequential Analysis (TSA).Treatment effects were presented as risk ratio (RR)for binary data and standardized mean difference (SMD) for continuous data with 95% confidence interval (CI).Results:We included 27 RCTs with a total of 1933 participants.Only one RCT had low risk of bias,and the others were of high or moderate risk of bias.For total effectiveness rate (proportion of total number of people who were cured or significant symptom improved),there was no significant difference between Western medicine (acyclovir,valacyclovir,adenosine cobalamin) and fire needling (risk ratio 1.05,95% CI 0.98 to 1.12;n =5).For pain relief (VAS scale):fire needling used alone showed lower scores than Western medicine (SMD-1.37,95% CI-1.77 to-0.97;n =2) or external medicine (diclofenac) (SMD-2.23,95% CI-2.81 to-1.64;n =1).Combination of fire needling and Western medicine was better than Western medicine alone in relieving pain (VAS scale) (SMD-2.19,95% CI-3.40 to-0.97,I2 =94%;n =4).Patients receiving fire needling had lower incidence of neuralgia than those receiving Western medicine (3.3% vs 26.7%,RR 0.09,95% Cl 0.01 to 0.82;n =1) at follow up for 30 days.No serious adverse events such as infection were reported.Conclusion:Fire needling appears to offer relief for alleviating pain in herpes zoster.As the sample size of included trials was small and the quality of studies was generally low,rigorous clinical trials with robust reporting and appropriate outcome measures are still needed.
基金"PUMC"Fellow award from Peking Union Medical Collage(PUMC)CAMS Initiative for Innovative Medicine(2016-I2M-1-006)
文摘The gut microbiota, the largest symbiotic ecosystem with the host, has been shown to play important roles in maintaining intestinal homeostasis. Dysbiosis of the gut microbiome is caused by the imbalance between the commensal and pathogenic microbiomes. The commensal microbiome regulates the maturation of the mucosal immune system, while the pathogenic microbiome causes immunity dysfunction, resulting in disease development.The gut mucosal immune system, which consists of lymph nodes, lamina propria and epithelial cells, constitutes a protective barrier for the integrity of the intestinal tract. The composition of the gut microbiota is under the surveillance of the normal mucosal immune system. Inflammation, which is caused by abnormal immune responses,influences the balance of the gut microbiome, resulting in intestinal diseases. In this review, we briefly outlined the interaction between the gut microbiota and the immune system and provided a reference for future studies.
基金supported by CAMS Initiative for Innovative Medicine of China,Grant/Award Number:No.2016-12M-1-006National Key R&D Program of China,Grant/Award Number:No.2017YFC1103603
文摘Background: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis. Methods: We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐ GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing. Results: Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia. Conclusion: Our mouse model of RA indicated that HFD increased ankle width and aggravated a therosclerosis a nd d yslipidemia, a nd t hat H CQ a lleviated t he d yslipidemia and atherosclerosis, but had no effect on ankle width.
基金This work was supported by National Natural Science Foundation of China(China)under grants 61373162Sichuan Science and Technology Support Project(China)under grants 2019YFG0183+1 种基金Visual Computing and Virtual Reality Sichuan Provincial Key Laboratory Project(China)under grants KJ201402was supported in part by the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid for Scientific Research(KAKENHI)(Japan)under Grant JP18K18044.
文摘A Large-Scale Heterogeneous Network(LS-HetNet)integrates different networks into one uniform network system to provide seamless one-world network coverage.In LS-HetNet,various devices use different technologies to access heterogeneous networks and generate a large amount of data.For dealing with a large number of access requirements,these data are usually stored in the HetNet Domain Management Server(HDMS)of the current domain,and HDMS uses a centralized Authentication/Authorization/Auditing(AAA)scheme to protect the data.However,this centralized method easily causes the data to be modified or disclosed.To address this issue,we propose a blockchain-empowered AAA scheme for accessing data of LS-HetNet.Firstly,the account address of the blockchain is used as the identity authentication,and the access control permission of data is redesigned and stored on the blockchain,then processes of AAA are redefined.Finally,the experimental model on Ethereum private chain is built,and the results show that the scheme is not only secure but also decentral,without tampering and trustworthiness.
文摘Objective:With using natural language processing (NLP) technology to analyze and process the text of "Treatise on Febrile Diseases (TFDs)"for the sake of finding important information, this paper attempts to apply NLP in the field of text mining of traditional Chinese medicine (TCM)literature. Materials and Methods:Based on the Python language, the experiment invoked the NLP toolkit such as Jieba, nltk, gensim,and sklearn library, and combined with Excel and Word software. The text of "TFDs" was sequentially cleaned, segmented, and moved the stopped words, and then implementing word frequency statistics and analysis, keyword extraction, named entity recognition (NER) and other operations, finally calculating text similarity. Results:Jieba can accurately identify the herbal name in "TFDs." Word frequency statistics based on the word segmentation found that "warm therapy" is an important treatment of "TFDs." Guizhi decoction is the main prescription,and five core decoctions are identified. Keyword extraction based on the term "frequency-inverse document frequency" algorithm is ideal.The accuracy of NER in "TFDs" is about 86%;latent semantic indexing model calculating the similarity,"Understanding of Synopsis of Golden Chamber (SGC)" is much more similar with "SGC" than with "TFDs." The results meet expectation. Conclusions:It lays a research foundation for applying NLP to the field of text mining of unstructured TCM literature. With the combination of deep learning technology,NLP as an important branch of artificial intelligence will have broader application prospective in the field of text mining in TCM literature and construction of TCM knowledge graph as well as TCM knowledge services.
基金supported by 2014‘‘PUMC Distinguished Professorship"research grant from Chinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)the Talent Recruitment Program from Institute of Laboratory Animal Sciences,CAMS and Comparative Medicine Center,PUMC,Beijing,China
文摘Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies(GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body's immune system and is likely related to genetic mutations in systemic autoimmune diseases.Next-generation sequencing(NGS) technology, with high-throughput capacity and accuracy,provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.
