National Free Traditional Chinese Medicine (TCM) HIV/AIDS Treatment Program had been carried out for more than 5 years, treating 9267 cases accumulately by 2009. We report the 3-year outcome on CD4+ lymphocyte count o...National Free Traditional Chinese Medicine (TCM) HIV/AIDS Treatment Program had been carried out for more than 5 years, treating 9267 cases accumulately by 2009. We report the 3-year outcome on CD4+ lymphocyte count of 807 cases of HIV/AIDS enrolled in the National Free TCM HIV/AIDS Treatment Pro- gram, the CD4+ lymphocyte count were measured every 6 month at 7 time points (0, 6, 12, 18, 24, 30, 36 month). The results showed that the overall CD4+ ly mphocyte count maintained stable at the 6th month and the 12th month, declined significantly at the 18th month, 24th month and 30th month, then elevated to the pre-treatment level at the 36th month. Patients with pre-treatment CD4+ lymphocyte count level 350/mm3 had CD4+ lymphocyte count declined significantly after all visits. In summary, combined treatment of Chinese herbal medicine and conventional therapy on HIV/AIDS suggested promising effect, but more evidences from larger, rigorous designed studies still needed to support the affirmative effect of TCM in the future.展开更多
The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are im...The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds.Here,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed.The antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction.In this reaction,the acrylate gelatin undergoes cross-linkage within seconds.Based on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential release.The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial strains.Moreover,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides.In a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization promotion.These results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.展开更多
Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor t...Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune response.On this basis,the editor can be combined with optical therapy to improve patient prognosis.In this study,the metal ratio was regulated in response to the nanocarrier of acid response type.Thus,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell membrane.Based on these results,the nanoparticles were cracked in an acidic environment and then released copper ions.Finally,the nanoparticles contributed to cuprotosis and immunogenic death.In addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without toxicity.The rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for immunotherapy.Moreover,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma.Above all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.展开更多
Osteoarthritis is associated with the significantly increased friction of the joint,which results in progressive and irreversible damage to the articular cartilage.A synergistic therapy integrating lubrication enhance...Osteoarthritis is associated with the significantly increased friction of the joint,which results in progressive and irreversible damage to the articular cartilage.A synergistic therapy integrating lubrication enhancement and drug delivery is recently proposed for the treatment of early-stage osteoarthritis.In the present study,bioinspired by the self-adhesion performance of mussels and super-lubrication property of articular cartilages,a biomimetic self-adhesive dopamine methacrylamide-poly(2-methacryloyloxyethyl phosphorylcholine)(DMA-MPC)copolymer was designed and synthesized via free radical polymerization.The copolymer was successfully modified onto the surface of biodegradable mesoporous silica nanoparticles(bMSNs)by the dip-coating method to prepare the dual-functional nanoparticles(bMSNs@DMA-MPC),which were evaluated using a series of surface characterizations including the transmission electron microscope(TEM),Fourier transform infrared(FTIR)spectrum,thermogravimetric analysis(TGA),X-ray photoelectron spectroscopy(XPS),etc.The tribological test and in vitro drug release test demonstrated that the developed nanoparticles were endowed with improved lubrication performance and achieved the sustained release of an anti-inflammatory drug,i.e.,diclofenac sodium(DS).In addition,the in vitro biodegradation test showed that the nanoparticles were almost completely biodegraded within 10 d.Furthermore,the dual-functional nanoparticles were biocompatible and effectively reduced the expression levels of two inflammation factors such as interleukin-1β(IL-1β)and interleukin-6(IL-6).In summary,the surface functionalized nanoparticles with improved lubrication and local drug release can be applied as a potential intra-articularly injected biolubricant for synergistic treatment of early-stage osteoarthritis.展开更多
To identify the chemical differences which lead to the different therapeutic effects of dried rehmannia root(DRR)and prepared rehmannia root(PRR),we compared the chemical composition of decoctions of randomly purchase...To identify the chemical differences which lead to the different therapeutic effects of dried rehmannia root(DRR)and prepared rehmannia root(PRR),we compared the chemical composition of decoctions of randomly purchased DRR and PRR using ultra performance liquid chromatography(UPLC)coupled with time-of-fight mass spectrometry and high performance liquid chromatography(HPLC)coupled with evaporative light scattering detection(ELSD)with the aid of multivariate statistical analysis.Both approaches clearly revealed compositional and quantitative differences between DRR and PRR.UPLC-MS data indicated stachyose,rehmaiono-side A(or rehmaionoside B),acteoside(or forsythiaside,or isoacteoside),6-O-coumaroylajugol(or 6-O-E-feruloylajugol,or 6-O-Z-feruloylajugol)as important discriminators between DRR and PRR decoctions.HPLC-ELSD analysis showed that the content of fructose in the decoctions of PRR was about four times greater than that of DRR(P<10^(-5)),while sucrose content in the decoctions of PRR was only about one seventh of that in DRR(P<0.01).Our results suggest that some compounds,such as fructose,stachyose and rehmaionoside,may be responsible for the differing therapeutic effects of DRR and PRR.Furthermore,improvements in quality control for PRR,which is currently lacking in the Chinese Pharmacopoeia,are recommended.展开更多
This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immun...This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treated continuously with TCM for 84 months. Information of 110 HIV/AIDS patients from 19 provinces and cities treated with TCM from 2004 to 2013 was collected. Changes in the indexes of CD4 counts ( ~〈 200, 201-350, 351-500 and 〉 500 cells/mm3) at five time points (0, 12, 36, 60 and 84 months) and different treatments [TCM and TCM plus antiretroviral therapy (ART)] were compared. Repeated measures test indicated no interaction between group and time (P 〉 0.05). Degrees of increasing and decreasing CD4 count of the two groups at four different frames were statistically significant compared with the baseline. The CD4 count between the two groups was not statistically significant. For CD4 count of ~〈 200 cells/ram3, the mean CD4 count changes were 21 and 28 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 201-350 celis/mm3, the mean CD4 count changes were 6 and 25 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 351 500 cells/mm3, the mean CD4 count changes were 13 and -7 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 〉 500 cells/mm3, the mean CD4 count changes were -34 and -17 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. Long-term use of TCM could maintain or slow the pace of declining CD4 counts in patients with HIV/AIDS, and may achieve lasting effectiveness.展开更多
Large-scale protein quantification has become a major proteomics application in many areas of biological and medical research.During the past years,different techniques have been developed,including gel-based such as ...Large-scale protein quantification has become a major proteomics application in many areas of biological and medical research.During the past years,different techniques have been developed,including gel-based such as differential in-gel electrophoresis(DIGE)and liquid chromatography-based such as isotope labeling and labelfree quantification.These quantitative proteomics tools hold significant promise for biomarker discovery,diagnostic and therapeutic applications.They are also important for research in functional genomics and systems biology towards basic understanding of molecular networks and pathway interactions.In this review,we summarize current technologies in quantitative proteomics and discuss recent applications of the technologies.展开更多
Movement of the renminbi (RMB) exchange rate is not only affected by economic factors, but also by political factors home and aboard. This paper analyzes the transmission mechanism of political cycles on the RMB exc...Movement of the renminbi (RMB) exchange rate is not only affected by economic factors, but also by political factors home and aboard. This paper analyzes the transmission mechanism of political cycles on the RMB exchange rate first, and then sets up a "political cycle spillover effect model" followed by an empirical analysis. We find that: (1) the US political cycle has a direct effect on the RMB exchange rate in the short run, which is mainly transmitted by capital flows and China's exchange rate policy control; (2) the RMB exchange rate changes periodically in accordance with the US presidential election and midterm election cycle, with the appreciation ratio significantly lower in the first year of the election cycle, while significantly higher in the year after the midterm election; (3) The effect of the political cycle will not be affected by which party holds power, though it will be affected if the president and parliament are ruled by the same party. This paper not only extends the research of the influencing factors of the RMB exchange rate to the political field, but also sets up a use theoretical model to analyze the impact of political issues on the RMB exchange rate, providing a new perspective to fully understand the external environment of RMB exchange rate reform.展开更多
文摘National Free Traditional Chinese Medicine (TCM) HIV/AIDS Treatment Program had been carried out for more than 5 years, treating 9267 cases accumulately by 2009. We report the 3-year outcome on CD4+ lymphocyte count of 807 cases of HIV/AIDS enrolled in the National Free TCM HIV/AIDS Treatment Pro- gram, the CD4+ lymphocyte count were measured every 6 month at 7 time points (0, 6, 12, 18, 24, 30, 36 month). The results showed that the overall CD4+ ly mphocyte count maintained stable at the 6th month and the 12th month, declined significantly at the 18th month, 24th month and 30th month, then elevated to the pre-treatment level at the 36th month. Patients with pre-treatment CD4+ lymphocyte count level 350/mm3 had CD4+ lymphocyte count declined significantly after all visits. In summary, combined treatment of Chinese herbal medicine and conventional therapy on HIV/AIDS suggested promising effect, but more evidences from larger, rigorous designed studies still needed to support the affirmative effect of TCM in the future.
基金support from the Research Foundation of Peking University School and Hospital of Stomatology(No.PKUSS20210113)the National Natural Science Foundation of China(Nos.51972003,and 52271127)+1 种基金the National Key Technologies R&D Program(No.2022YFC2403203-3)Intergovernmental International Cooperation Project of Beijing Municipal Science and Technology Commission(No.Z221100002722004).
文摘The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds.Here,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed.The antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction.In this reaction,the acrylate gelatin undergoes cross-linkage within seconds.Based on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential release.The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial strains.Moreover,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides.In a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization promotion.These results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.
基金the National Key Research and Development Program of China(No.2022YFC2403203-3)Jilin Province Department of Finance(No.jcsz2023481-13)+2 种基金the National Natural Science Foundation of China(Nos.51972003 and 52271127)the Intergovernmental International Co-operation Project of Beijing Municipal Science and Technology Commission(No.Z221100002722004)the 2023 Management Research Project(No.YS040223).
文摘Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic death.Here,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune response.On this basis,the editor can be combined with optical therapy to improve patient prognosis.In this study,the metal ratio was regulated in response to the nanocarrier of acid response type.Thus,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell membrane.Based on these results,the nanoparticles were cracked in an acidic environment and then released copper ions.Finally,the nanoparticles contributed to cuprotosis and immunogenic death.In addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without toxicity.The rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for immunotherapy.Moreover,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma.Above all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.
基金financially supported by the National Natural Science Foundation of China(52022043 and 21868011)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program(20191080593)+2 种基金Precision Medicine Foundation,Tsinghua University,China(10001020107)the National Key R&D Program of China(2017YFC1103800)Research Fund of State Key Laboratory of Tribology,Tsinghua University,China(SKLT2022C18).
文摘Osteoarthritis is associated with the significantly increased friction of the joint,which results in progressive and irreversible damage to the articular cartilage.A synergistic therapy integrating lubrication enhancement and drug delivery is recently proposed for the treatment of early-stage osteoarthritis.In the present study,bioinspired by the self-adhesion performance of mussels and super-lubrication property of articular cartilages,a biomimetic self-adhesive dopamine methacrylamide-poly(2-methacryloyloxyethyl phosphorylcholine)(DMA-MPC)copolymer was designed and synthesized via free radical polymerization.The copolymer was successfully modified onto the surface of biodegradable mesoporous silica nanoparticles(bMSNs)by the dip-coating method to prepare the dual-functional nanoparticles(bMSNs@DMA-MPC),which were evaluated using a series of surface characterizations including the transmission electron microscope(TEM),Fourier transform infrared(FTIR)spectrum,thermogravimetric analysis(TGA),X-ray photoelectron spectroscopy(XPS),etc.The tribological test and in vitro drug release test demonstrated that the developed nanoparticles were endowed with improved lubrication performance and achieved the sustained release of an anti-inflammatory drug,i.e.,diclofenac sodium(DS).In addition,the in vitro biodegradation test showed that the nanoparticles were almost completely biodegraded within 10 d.Furthermore,the dual-functional nanoparticles were biocompatible and effectively reduced the expression levels of two inflammation factors such as interleukin-1β(IL-1β)and interleukin-6(IL-6).In summary,the surface functionalized nanoparticles with improved lubrication and local drug release can be applied as a potential intra-articularly injected biolubricant for synergistic treatment of early-stage osteoarthritis.
基金The authors are grateful for financial support from the National Nature Science Foundation of China(Grant Nos.81073161,81130067 and 30730112)the National Basic Research Program of China(Grant No.2011CB505304)+1 种基金the Natural Science Foundation of Beijing(Grant No.7112110)for technical support from Mr.Yong Wang and other technologists of Waters China Ltd.
文摘To identify the chemical differences which lead to the different therapeutic effects of dried rehmannia root(DRR)and prepared rehmannia root(PRR),we compared the chemical composition of decoctions of randomly purchased DRR and PRR using ultra performance liquid chromatography(UPLC)coupled with time-of-fight mass spectrometry and high performance liquid chromatography(HPLC)coupled with evaporative light scattering detection(ELSD)with the aid of multivariate statistical analysis.Both approaches clearly revealed compositional and quantitative differences between DRR and PRR.UPLC-MS data indicated stachyose,rehmaiono-side A(or rehmaionoside B),acteoside(or forsythiaside,or isoacteoside),6-O-coumaroylajugol(or 6-O-E-feruloylajugol,or 6-O-Z-feruloylajugol)as important discriminators between DRR and PRR decoctions.HPLC-ELSD analysis showed that the content of fructose in the decoctions of PRR was about four times greater than that of DRR(P<10^(-5)),while sucrose content in the decoctions of PRR was only about one seventh of that in DRR(P<0.01).Our results suggest that some compounds,such as fructose,stachyose and rehmaionoside,may be responsible for the differing therapeutic effects of DRR and PRR.Furthermore,improvements in quality control for PRR,which is currently lacking in the Chinese Pharmacopoeia,are recommended.
文摘This study aimed to evaluate the therapeutic effect of traditional Chinese medicine (TCM) by observing the changes in CD4 T-lymphocyte cell count of 110 cases with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treated continuously with TCM for 84 months. Information of 110 HIV/AIDS patients from 19 provinces and cities treated with TCM from 2004 to 2013 was collected. Changes in the indexes of CD4 counts ( ~〈 200, 201-350, 351-500 and 〉 500 cells/mm3) at five time points (0, 12, 36, 60 and 84 months) and different treatments [TCM and TCM plus antiretroviral therapy (ART)] were compared. Repeated measures test indicated no interaction between group and time (P 〉 0.05). Degrees of increasing and decreasing CD4 count of the two groups at four different frames were statistically significant compared with the baseline. The CD4 count between the two groups was not statistically significant. For CD4 count of ~〈 200 cells/ram3, the mean CD4 count changes were 21 and 28 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 201-350 celis/mm3, the mean CD4 count changes were 6 and 25 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 351 500 cells/mm3, the mean CD4 count changes were 13 and -7 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. For CD4 count of 〉 500 cells/mm3, the mean CD4 count changes were -34 and -17 cells/mm3 per year for the TCM group and TCM plus ART group, respectively. Long-term use of TCM could maintain or slow the pace of declining CD4 counts in patients with HIV/AIDS, and may achieve lasting effectiveness.
基金The proteomics work in our collaborative group was supported by funding from the University of Florida,the National Science Foundation(MCB 0818051,CAREER 0845162)the National Institute of Health(1S10RR025418-01)of the USA to S CHEN,and the National Science Foundation of China(No.30871566)the Natural Science Foundation of Heilongjiang Province(No.C2007-37)to H LI.
文摘Large-scale protein quantification has become a major proteomics application in many areas of biological and medical research.During the past years,different techniques have been developed,including gel-based such as differential in-gel electrophoresis(DIGE)and liquid chromatography-based such as isotope labeling and labelfree quantification.These quantitative proteomics tools hold significant promise for biomarker discovery,diagnostic and therapeutic applications.They are also important for research in functional genomics and systems biology towards basic understanding of molecular networks and pathway interactions.In this review,we summarize current technologies in quantitative proteomics and discuss recent applications of the technologies.
文摘Movement of the renminbi (RMB) exchange rate is not only affected by economic factors, but also by political factors home and aboard. This paper analyzes the transmission mechanism of political cycles on the RMB exchange rate first, and then sets up a "political cycle spillover effect model" followed by an empirical analysis. We find that: (1) the US political cycle has a direct effect on the RMB exchange rate in the short run, which is mainly transmitted by capital flows and China's exchange rate policy control; (2) the RMB exchange rate changes periodically in accordance with the US presidential election and midterm election cycle, with the appreciation ratio significantly lower in the first year of the election cycle, while significantly higher in the year after the midterm election; (3) The effect of the political cycle will not be affected by which party holds power, though it will be affected if the president and parliament are ruled by the same party. This paper not only extends the research of the influencing factors of the RMB exchange rate to the political field, but also sets up a use theoretical model to analyze the impact of political issues on the RMB exchange rate, providing a new perspective to fully understand the external environment of RMB exchange rate reform.