Objective Qing Fu Juan Bi Tang(QFJBT)is an anti-arthritic Chinese medicine formula consisting of five herbs:Aconiti Lateralis Radix Praeparata(Fu Zi,附子),Sinomenii Caulis(Qing Feng Teng,青风藤),Astragali Radix(Huang ...Objective Qing Fu Juan Bi Tang(QFJBT)is an anti-arthritic Chinese medicine formula consisting of five herbs:Aconiti Lateralis Radix Praeparata(Fu Zi,附子),Sinomenii Caulis(Qing Feng Teng,青风藤),Astragali Radix(Huang Qi,黄芪),Paeoniae Radix Alba(Bai Shao,白芍)and Moutan Cortex(Mu Dan Pi,牡丹皮),which have well-established histories of use for treatment of rheumatic and arthritic diseases.We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis(RA).Methods The combinative approaches of chemical assessment,toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT.Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents,potent anti-inflammatory and antinociceptive activities,and favorable safety profile.Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography(HPLC)demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent.General toxicological studies showed a favorable safety profile of QFJBT.The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose.In the chronic oral toxicity study,the results of laboratory investigation showed that QFJBT at doses of 3.89,6.80 and 9.72 g/kg body weight(equivalent to 40,70 and 100-fold clinical doses,respectively)caused no changes in all hematological parameters and blood biochemical parameters of rats.No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT.Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.展开更多
Objective To establish a rat model of Spinal Cord Injury(SCI)with the pathopattern of Qi-deficiency and Blood-stasis(QDBS)in Traditional Chinese Medicine(TCM),and then assess its feasibility.Methods Swimming exhaustio...Objective To establish a rat model of Spinal Cord Injury(SCI)with the pathopattern of Qi-deficiency and Blood-stasis(QDBS)in Traditional Chinese Medicine(TCM),and then assess its feasibility.Methods Swimming exhaustion method and Rubrospinal Tract(RST)transection were combined to establish arat model of SCI with pathopattern of QDBS in TCM.Macroscopic representation,including the body weight,food intake and tongue scores,was recorded.Behavioristics was scored with spontaneous vertical exploration test.Hemorrheology was analyzed using hemorheological analyzer and morphology of spinal cord was observed.The feasibility of the model was confirmed on the basis of the reversion caused by administration of Bu Yang Huan Wu Decoction(BYHWD).Results The findings in the QDBS group were consistent with the symptoms of QDBS syndrome,including reduced body weight,food intake,and forelimb utilization rate and increased tongue scores.However,the corresponding findings in the BYHWD group were superior to those in the QDBS group after35d(P<0.05).In comparison with the control group,the QDBS group showed higher whole blood viscosity and hematocrit values(P<0.05)and a lower red blood cell(RBC)deformability index(P<0.05),while the corresponding findings in the BYHWD group were close to those in the control group.An eminence or induration appeared in the injured spinal cord,which was suspected to be vacuoles or a scar.Hematoxylin-eosin staining showed that the R/T ratio in the BYHWD group was higher than that in the QDBS group(P<0.05).Conclusion Swimming exhaustion method combined with RST transection operation can successfully establish a rat model of SCI with pathopattern of QDBS.展开更多
Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiti...Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.展开更多
We aimed to access if acute graft-versus-host disease （aGVHD） in liver transplantation recipients of hepatocellular carcinoma （HCC） might develop a graft-versus-tumor effect （GVT） other than immunological damage...We aimed to access if acute graft-versus-host disease （aGVHD） in liver transplantation recipients of hepatocellular carcinoma （HCC） might develop a graft-versus-tumor effect （GVT） other than immunological damage which would benefit prophylaxis of tumor recurrence. Methods： Dynamic observation of 3 cases of liver transplantation recipients of HCC and cirrhosis, which developed manifestations of fever, skin rash, watery diarrhea, pancytopenia and were finally diagnosed as aGVHD. Two of which got recovered from intravenously pulse methylprednisolone, high-dose intravenous immunoglobulin, antibiotics administration simultaneously and promptly withdrawal of oral immunosuppressants. Two survivors were follow-up regularly with biological monitoring and imaging surveillance for tumor recurrence thereafter. Results： Two recipients survived healthily with stable liver graft function and normal serum AFP level and blood routine test. No sign of tumor recurrence was found in repeat imaging examinations for liver graft, lung, brain and other tissue or organs within a period of 96 months and 17 months to date, respectively. Conclusien： Despite of the fatal damage to according organs and tissue, it suggest that aGVHD in liver recipients of HCC may also develop a GVT effect and benefit prophylaxis of tumor recurrence and result in a long-term healthy recipients survival.展开更多
Chinese Medicine(CM)has been widely used as an important avenue for disease prevention and treatment in China especially in the form of CM prescriptions combining sets of herbs to address patients’symptoms and syndro...Chinese Medicine(CM)has been widely used as an important avenue for disease prevention and treatment in China especially in the form of CM prescriptions combining sets of herbs to address patients’symptoms and syndromes.However,the selection and compatibility of herbs are complex and abstract due to intrinsic relationships between herbal properties and their overall functions.Network analysis is applied to demonstrate the complex relationships between individual herbal efficacy and the overall function of CM prescriptions.To illustrate their connections and correlations,prescription function(PF),prescription herb(PH),and herbal efficacy(HE)intranetworks are proposed based on CM theory to identify relationships between herbs and prescriptions.These three networks are then connected by PF-PH and PH-HE interlayer networks adopting herb dosage to form a multidimensional heterogeneous network,a Prescription-Herb-Function Network(PHFN).The network is applied to 112 classic prescriptions from Treatise on Exogenous Febrile and Miscellaneous Diseases to illustrate the application of PHFN.The PHFN is constructed including 146 functions in PF intra network,89 herbs in the PH intra network,and 163 herbal efficacies in the HE intra network.The results show that herb pairs with synergistic actions have stronger relevance,such as licorice-cassia twig,licorice-Chinese date,fresh ginger-Chinese date,etc.The integration of dosage to the network helps to indicate the main herbs for cluster analysis and automatic formulation.PHFN also reveals the internal relationships between the functions of prescriptions and composed herbal efficacies.展开更多
When longitudinal data contains outliers, the classical least-squares approach is known to be not robust. To solve this issue, the exponential squared loss (ESL) function with a tuning parameter has been investigated ...When longitudinal data contains outliers, the classical least-squares approach is known to be not robust. To solve this issue, the exponential squared loss (ESL) function with a tuning parameter has been investigated for longitudinal data. However, to our knowledge, there is no paper to investigate the robust estimation procedure against outliers within the framework of mean-covariance regression analysis for longitudinal data using the ESL function. In this paper, we propose a robust estimation approach for the model parameters of the mean and generalized autoregressive parameters with longitudinal data based on the ESL function. The proposed estimators can be shown to be asymptotically normal under certain conditions. Moreover, we develop an iteratively reweighted least squares (IRLS) algorithm to calculate the parameter estimates, and the balance between the robustness and efficiency can be achieved by choosing appropriate data adaptive tuning parameters. Simulation studies and real data analysis are carried out to illustrate the finite sample performance of the proposed approach.展开更多
Angiogenesis is critical from early development through the progression of life-threatening diseases.In rheu-matoid arthritis(RA),angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the ...Angiogenesis is critical from early development through the progression of life-threatening diseases.In rheu-matoid arthritis(RA),angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the progression of synovitis.However,the intricate mechanisms underlying these changes remain poorly under-stood.Despite the development of numerous anti-angiogenic agents,their clinical efficacy is often compromised by adverse effects and the emergence of adaptive resistance,leading to disease relapse or progression.Nano-medicine has gained significant attention owing to its excellent biocompatibility,precise biological targeting,and enhanced therapeutic outcomes.Anti-angiogenic nanoagents have shown transformative potential in treating cancer and retinal diseases.Nevertheless,a comprehensive review addressing the fundamental mech-anisms of anti-angiogenic nanoagents in RA has yet to be undertaken.Herein,this review provides an in-depth description of the unique structural and functional aspects of pathological angiogenesis in RA and its negative consequences.The mechanisms of pro-angiogenic mediators contributing to RA angiogenesis are further explored.Subsequently,biological activities of nanomedicines for the treatment of RA are summarized.Finally,the cutting-edge developments in the anti-angiogenic nanoagents of RA engineered based on these mechanisms and bioactivities are outlined.A helpful introduction to anti-angiogenic strategies for treatment of RA,which may offer novel perspectives for the development of nanoagents,is opening a new horizon in the fight against RA.展开更多
基金support from the National Natural Science Foundation of China(No.81704065)China Postdoctoral Science Foundation(No.2016M600632 and No.2017T100604)+3 种基金Hunan Provincial Natural Science Foundation(No.2017JJ3239 and No.2018JJ2293)Hunan Education Department’s Science&Research Project(No.17K069)Hunan Provincial Science&Research Project of Chinese Medicine(No.201790)National First-class Disciple Construction Project of Chinese Medicine of Hunan University of Chinese Medicine
文摘Objective Qing Fu Juan Bi Tang(QFJBT)is an anti-arthritic Chinese medicine formula consisting of five herbs:Aconiti Lateralis Radix Praeparata(Fu Zi,附子),Sinomenii Caulis(Qing Feng Teng,青风藤),Astragali Radix(Huang Qi,黄芪),Paeoniae Radix Alba(Bai Shao,白芍)and Moutan Cortex(Mu Dan Pi,牡丹皮),which have well-established histories of use for treatment of rheumatic and arthritic diseases.We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis(RA).Methods The combinative approaches of chemical assessment,toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT.Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents,potent anti-inflammatory and antinociceptive activities,and favorable safety profile.Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography(HPLC)demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent.General toxicological studies showed a favorable safety profile of QFJBT.The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose.In the chronic oral toxicity study,the results of laboratory investigation showed that QFJBT at doses of 3.89,6.80 and 9.72 g/kg body weight(equivalent to 40,70 and 100-fold clinical doses,respectively)caused no changes in all hematological parameters and blood biochemical parameters of rats.No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT.Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.
基金funding support from the National Natural Science Foundation of China (No. 81302899, 81373551 and 81603512)the Key Science and Research Program of Hunan Department of Science and Technology (No. 2012TF-1005)
文摘Objective To establish a rat model of Spinal Cord Injury(SCI)with the pathopattern of Qi-deficiency and Blood-stasis(QDBS)in Traditional Chinese Medicine(TCM),and then assess its feasibility.Methods Swimming exhaustion method and Rubrospinal Tract(RST)transection were combined to establish arat model of SCI with pathopattern of QDBS in TCM.Macroscopic representation,including the body weight,food intake and tongue scores,was recorded.Behavioristics was scored with spontaneous vertical exploration test.Hemorrheology was analyzed using hemorheological analyzer and morphology of spinal cord was observed.The feasibility of the model was confirmed on the basis of the reversion caused by administration of Bu Yang Huan Wu Decoction(BYHWD).Results The findings in the QDBS group were consistent with the symptoms of QDBS syndrome,including reduced body weight,food intake,and forelimb utilization rate and increased tongue scores.However,the corresponding findings in the BYHWD group were superior to those in the QDBS group after35d(P<0.05).In comparison with the control group,the QDBS group showed higher whole blood viscosity and hematocrit values(P<0.05)and a lower red blood cell(RBC)deformability index(P<0.05),while the corresponding findings in the BYHWD group were close to those in the control group.An eminence or induration appeared in the injured spinal cord,which was suspected to be vacuoles or a scar.Hematoxylin-eosin staining showed that the R/T ratio in the BYHWD group was higher than that in the QDBS group(P<0.05).Conclusion Swimming exhaustion method combined with RST transection operation can successfully establish a rat model of SCI with pathopattern of QDBS.
基金funded by grants from the National Natural Science Foundation of China(Grant No.:82274506)the China Postdoctoral Science Foundation(Grant No.:2022M721128)+6 种基金the Science and Technology Innovation Program of Hunan,China(Grant No.:2021RC4035)the Natural Science Foundation of Hunan,China(Grant No.:2023JJ40477)the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine(HNUCM),China(Grant No.:22JBZ003)was financially supported by the Furong Distinguished Scholar Program of Hunan,China(Program No.:XJT[2020]58)the 121 Training Project for Innovative Talents of Hunan,China(Project No.:XRSH[2019]192)the Chinese Academy of Engineering Academician Liang Liu's Workstation Project,China(Project No.:KH[2023]3-23YS001)the World First-class Discipline Incubation Project of HNUCM,China(Project No.:XJF[2022]57)。
文摘Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(t_(1/2)),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.
文摘We aimed to access if acute graft-versus-host disease （aGVHD） in liver transplantation recipients of hepatocellular carcinoma （HCC） might develop a graft-versus-tumor effect （GVT） other than immunological damage which would benefit prophylaxis of tumor recurrence. Methods： Dynamic observation of 3 cases of liver transplantation recipients of HCC and cirrhosis, which developed manifestations of fever, skin rash, watery diarrhea, pancytopenia and were finally diagnosed as aGVHD. Two of which got recovered from intravenously pulse methylprednisolone, high-dose intravenous immunoglobulin, antibiotics administration simultaneously and promptly withdrawal of oral immunosuppressants. Two survivors were follow-up regularly with biological monitoring and imaging surveillance for tumor recurrence thereafter. Results： Two recipients survived healthily with stable liver graft function and normal serum AFP level and blood routine test. No sign of tumor recurrence was found in repeat imaging examinations for liver graft, lung, brain and other tissue or organs within a period of 96 months and 17 months to date, respectively. Conclusien： Despite of the fatal damage to according organs and tissue, it suggest that aGVHD in liver recipients of HCC may also develop a GVT effect and benefit prophylaxis of tumor recurrence and result in a long-term healthy recipients survival.
文摘Chinese Medicine(CM)has been widely used as an important avenue for disease prevention and treatment in China especially in the form of CM prescriptions combining sets of herbs to address patients’symptoms and syndromes.However,the selection and compatibility of herbs are complex and abstract due to intrinsic relationships between herbal properties and their overall functions.Network analysis is applied to demonstrate the complex relationships between individual herbal efficacy and the overall function of CM prescriptions.To illustrate their connections and correlations,prescription function(PF),prescription herb(PH),and herbal efficacy(HE)intranetworks are proposed based on CM theory to identify relationships between herbs and prescriptions.These three networks are then connected by PF-PH and PH-HE interlayer networks adopting herb dosage to form a multidimensional heterogeneous network,a Prescription-Herb-Function Network(PHFN).The network is applied to 112 classic prescriptions from Treatise on Exogenous Febrile and Miscellaneous Diseases to illustrate the application of PHFN.The PHFN is constructed including 146 functions in PF intra network,89 herbs in the PH intra network,and 163 herbal efficacies in the HE intra network.The results show that herb pairs with synergistic actions have stronger relevance,such as licorice-cassia twig,licorice-Chinese date,fresh ginger-Chinese date,etc.The integration of dosage to the network helps to indicate the main herbs for cluster analysis and automatic formulation.PHFN also reveals the internal relationships between the functions of prescriptions and composed herbal efficacies.
文摘When longitudinal data contains outliers, the classical least-squares approach is known to be not robust. To solve this issue, the exponential squared loss (ESL) function with a tuning parameter has been investigated for longitudinal data. However, to our knowledge, there is no paper to investigate the robust estimation procedure against outliers within the framework of mean-covariance regression analysis for longitudinal data using the ESL function. In this paper, we propose a robust estimation approach for the model parameters of the mean and generalized autoregressive parameters with longitudinal data based on the ESL function. The proposed estimators can be shown to be asymptotically normal under certain conditions. Moreover, we develop an iteratively reweighted least squares (IRLS) algorithm to calculate the parameter estimates, and the balance between the robustness and efficiency can be achieved by choosing appropriate data adaptive tuning parameters. Simulation studies and real data analysis are carried out to illustrate the finite sample performance of the proposed approach.
基金the National Natural Science Foundation of China,China(82274506,82373871)the Science and Technology Innovation Program of Hunan Province,China,Hunan(2020SK1020,2021RC4035)+6 种基金the Natural Science Foundation of Hunan,China,Hunan(2024JJ5298)the Key Research and Development Pro-gram of Hunan Province,China,Hunan(2024JK2114)the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine(HNUCM),China,Hunan(22JBZ003)the Furong Distinguished Scholar Program of Hunan,China,Hunan(XJT[2020]58)the 121 Training Project for Innovative Talents of Hunan,China,Hunan(XRSH[2019]192)the Chinese Academy of Engineering Academician Liang Liu’s Workstation of HNUCM,China,Hunan(KH[2023]3-23YS001)the World First-class Discipline Incubation Project of HNUCM,China,Hunan(XJF[2022]57).
文摘Angiogenesis is critical from early development through the progression of life-threatening diseases.In rheu-matoid arthritis(RA),angiogenesis is markedly heightened and undergoes aberrant changes that exacerbate the progression of synovitis.However,the intricate mechanisms underlying these changes remain poorly under-stood.Despite the development of numerous anti-angiogenic agents,their clinical efficacy is often compromised by adverse effects and the emergence of adaptive resistance,leading to disease relapse or progression.Nano-medicine has gained significant attention owing to its excellent biocompatibility,precise biological targeting,and enhanced therapeutic outcomes.Anti-angiogenic nanoagents have shown transformative potential in treating cancer and retinal diseases.Nevertheless,a comprehensive review addressing the fundamental mech-anisms of anti-angiogenic nanoagents in RA has yet to be undertaken.Herein,this review provides an in-depth description of the unique structural and functional aspects of pathological angiogenesis in RA and its negative consequences.The mechanisms of pro-angiogenic mediators contributing to RA angiogenesis are further explored.Subsequently,biological activities of nanomedicines for the treatment of RA are summarized.Finally,the cutting-edge developments in the anti-angiogenic nanoagents of RA engineered based on these mechanisms and bioactivities are outlined.A helpful introduction to anti-angiogenic strategies for treatment of RA,which may offer novel perspectives for the development of nanoagents,is opening a new horizon in the fight against RA.
