Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic chang...Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.展开更多
OBJECTIVE： To investigate the traditional Chinese Medicine （TCM） etiology and pathogenesis of ac- quired immune deficiency syndrome （AIDS） by 18-month observation of Chinese rhesus macaques infected with simian i...OBJECTIVE： To investigate the traditional Chinese Medicine （TCM） etiology and pathogenesis of ac- quired immune deficiency syndrome （AIDS） by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus （SIV） mac239. METHODS： Thirty-five healthy Chinese rhesus ma- caques were divided into a model group （n=30） and a control group （n=5）. The model was estab- lished by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV in- fection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lym-phocyte subsets, plasma triiodothyronine （T3）, tet- raiodothyronine （14）, adrenocorticotropic hormone （ACTH） and cortisol （Cor） were tested periodically during the experiment. RESULTS： During the acute infection period of SIV, model monkeys temporarily showed clinical symp- toms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4~ T-lymphocytes were observed but levels of T3, 14, Cot, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infec- tion showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed nor- mal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of 13 and Cot. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3appeared. CONCLUSION： The results suggest that the rhesus monkey SIWSAIDS model can be applied to re- search on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the in- vasion of SIV virus, incubation of the virus, balance between virus and healthy ＂Qi＂, damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.展开更多
OBJECTIVE:To explore the efficacy of integrating Traditional Chinese Medicine(TCM)and anti-retroviral therapy(ART),a customized combination of different classes of medications which was also called cock-tail treatment...OBJECTIVE:To explore the efficacy of integrating Traditional Chinese Medicine(TCM)and anti-retroviral therapy(ART),a customized combination of different classes of medications which was also called cock-tail treatment,on the immunological nonresponse(INR)in people living with human immunodeficiency virus(HIV)(PLWH).METHODS:Relevant literature in databases such as China National Knowledge Infrastructure Database(CNKI),Wanfang Digital Journal,Chinese Medical Journal Database(CMJD),Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane,and Embase was reviewed by two independent investigators.Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3.RESULTS:Nine randomized controlled trials(RCTs)with 1078 patients were analyzed.Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group[mean difference(MD)=13.51,95%confidence interval(CI):7.42-19.60,P<0.0001].There was no significant difference between the treated and control groups after 3 months(MD=25.31,95%CI:-2.78 to 53.41,P=0.08).However,after 6 and 12 months,the response of the treatment group was superior to the control group(MD=27.45,95%CI:7.09-47.81,P=0.008 and MD=27.34,95%CI:6.31–48.37,P=0.01,respectively).The clinical efficacy of the treatment group was also higher than that of the control group(RR=1.75,95%CI:1.16-2.65,P=0.007).However,CD45 RO and CD45 RA T cell counts did not differ significantly between the two groups(MD=12.37,95%CI:-6.71 to 31.45,P=0.20 and MD=5.67,95%CI:-3.00 to14.35,P=0.20,respectively).CONCLUSION:The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus,is beneficial and has potential use for improving INR in PLWH.However,large-scale RCTs are required to provide evidence for optimal intervention strategies.展开更多
OBJECTIVE:To evaluate the effects of the Wenshen Jianpi recipe(温肾健脾方,WJR)on immune reconstruction and natural killer(NK)cells in immunological non-responders(INRs)of people living with human immunodeficiency viru...OBJECTIVE:To evaluate the effects of the Wenshen Jianpi recipe(温肾健脾方,WJR)on immune reconstruction and natural killer(NK)cells in immunological non-responders(INRs)of people living with human immunodeficiency virus(HIV)(PLWH)and propose new therapeutic strategies for HIV.METHODS:Based on Traditional Chinese Medicine treatment principle“invigorating Qi and warming Yang in the spleen and kidneys”,WJR combined with antiretroviral therapy(ART)therapy was performed in a randomized,double-blind,placebo-controlled study of 60 patients with non-responders.The randomized process was executed by the Clinical Evaluation Center of China Academy of Chinese Medical Sciences.Sixty patients who met the inclusion criteria obtained random numbers(that is the drug number)was randomly divided into a treatment group and a placebo control group according to a 1∶1 ratio.CD4+T cell counts and natural killer(NK)cells counts were evaluated at baseline and 12-week,24-week follow-ups.RESULTS:Four participants received random numbers and did not enter the group due to the patient’s own reasons.A total of 56 patients were enrolled,including 28 in the treatment group and 28 in the control group.CD4+T cell counts in the treatment group were significantly increased at week 24(P=0.01<0.05),which were significantly higher than those in the control group(P=0.01<0.05).Although no significant differences were observed between two groups,the CD56bri CD16-NK cell counts in the treatment group were significantly increased after duration.and CD56dim CD16+NK cell counts in the treatment group were significantly higher than those in the control group after 24 weeks of treatment(P=0.025<0.05).As compared with the control group,the treatment group had significantly lower CD56neg CD16+NK cell counts after 24 weeks of treatment(P=0.023<0.05).CONCLUSIONS:WJR promotes the immune reconstruction of INRs and redistribution of NK cell subsets,notably decreasing CD56neg CD16+NK cell counts in INRs.However,the redistribution of NK cell subsets is not beneficial for immune reconstruction in INRs.Further large-scale RCTs are required to evaluate the effect of WJR on immune recovery in INRs and decipher the underlying mechanism.展开更多
AIM To compare high-resolution computed tomography(HRCT) findings between humoral primary immunodeficiencies(hPIDs) subtypes; to correlate these findings to pulmonary function tests(PFTs).METHODS We retrospectively id...AIM To compare high-resolution computed tomography(HRCT) findings between humoral primary immunodeficiencies(hPIDs) subtypes; to correlate these findings to pulmonary function tests(PFTs).METHODS We retrospectively identified 52 consecutive adult patients with hPIDs who underwent 64-row HRCT and PFTs at the time of diagnosis. On a per-patient basis, an experienced radiologist recorded airway abnormalities(bronchiectasis,airway wall thickening, mucus plugging, tree-in-bud, and air-trapping) and parenchymal-interstitial abnormalities(consolidations, ground-glass opacities,linear and/or irregular opacities, nodules, and bullae/cysts) found on HRCT.The chi-square test was performed to compare the prevalence of each abnormality among patients with different subtypes of hPIDs. Overall logistic regression analysis was performed to assess whether HRCT findings predicted obstructive and/or restrictive PFTs results(absent-to-mild vs moderate-tosevere).RESULTS Thirty-eight of the 52 patients with hPIDs showed common variable immunodeficiency disorders(CVID), while the remaining 14 had CVID-like conditions(i.e., 11 had isolated IgG subclass deficiencies and 3 had selective IgA deficiencies). The prevalence of most HRCT abnormalities was not significantly different between CVID and CVID-like patients(P > 0.05), except for linear and/or irregular opacities(prevalence of 31.6% in the CVID group and 0 in the CVID-like group; P = 0.0427). Airway wall thickening was the most frequent HRCT abnormality found in both CVID and CVID-like patients(71% of cases in both groups). The presence of tree-in-bud abnormalities was an independent predictor of moderate-to-severe obstructive defects at PFTs(Odds Ratio, OR, of 18.75, P < 0.05), while the presence of linear and/or irregular opacities was an independent predictor of restrictive defects at PFTs(OR = 13.00; P < 0.05).CONCLUSION CVID and CVID-like patients showed similar HRCT findings. Tree-in-bud and linear and/or irregular opacities predicted higher risks of, respectively,obstructive and restrictive defects at PFTs.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82271963(to HJL),81771806(to HJL),61936013(to HJL),82001914(to ZCT),81871511(to HZ)National Key R&D Program of China,No.2021YFA1301603(to ZCT)the Natural Science Foundation of Beijing,No.7212051(to HJL).
文摘Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.
基金Supported by the National Science and Technology Major Project "Optimization for prescription of anti-HIV Chinese medicine and the study on animal model for AIDS with TCM symptoms(No.2008ZX10005-005)National Key Discipline Construction funding for clinical basic of TCM in Guangzhou university of Chinese Medicine
文摘OBJECTIVE： To investigate the traditional Chinese Medicine （TCM） etiology and pathogenesis of ac- quired immune deficiency syndrome （AIDS） by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus （SIV） mac239. METHODS： Thirty-five healthy Chinese rhesus ma- caques were divided into a model group （n=30） and a control group （n=5）. The model was estab- lished by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV in- fection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lym-phocyte subsets, plasma triiodothyronine （T3）, tet- raiodothyronine （14）, adrenocorticotropic hormone （ACTH） and cortisol （Cor） were tested periodically during the experiment. RESULTS： During the acute infection period of SIV, model monkeys temporarily showed clinical symp- toms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4~ T-lymphocytes were observed but levels of T3, 14, Cot, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infec- tion showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed nor- mal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of 13 and Cot. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3appeared. CONCLUSION： The results suggest that the rhesus monkey SIWSAIDS model can be applied to re- search on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the in- vasion of SIV virus, incubation of the virus, balance between virus and healthy ＂Qi＂, damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.
基金Supported by National Science and Technology Major Project of China During the 13th Five-year Plan Period:New Adjuvant Strategies of Traditional Chinese Medicine on Immune Reconstruction for Long-term ART-treated People Living with HIV(No.2017ZX10205501)Study of AIDS-related Early Biomarkers for Disease Progression and Epidemic Predicting Model(No.2017ZX10201101)the Beijing Excellent Talent Plan(No.2018000021223ZK04)。
文摘OBJECTIVE:To explore the efficacy of integrating Traditional Chinese Medicine(TCM)and anti-retroviral therapy(ART),a customized combination of different classes of medications which was also called cock-tail treatment,on the immunological nonresponse(INR)in people living with human immunodeficiency virus(HIV)(PLWH).METHODS:Relevant literature in databases such as China National Knowledge Infrastructure Database(CNKI),Wanfang Digital Journal,Chinese Medical Journal Database(CMJD),Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane,and Embase was reviewed by two independent investigators.Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3.RESULTS:Nine randomized controlled trials(RCTs)with 1078 patients were analyzed.Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group[mean difference(MD)=13.51,95%confidence interval(CI):7.42-19.60,P<0.0001].There was no significant difference between the treated and control groups after 3 months(MD=25.31,95%CI:-2.78 to 53.41,P=0.08).However,after 6 and 12 months,the response of the treatment group was superior to the control group(MD=27.45,95%CI:7.09-47.81,P=0.008 and MD=27.34,95%CI:6.31–48.37,P=0.01,respectively).The clinical efficacy of the treatment group was also higher than that of the control group(RR=1.75,95%CI:1.16-2.65,P=0.007).However,CD45 RO and CD45 RA T cell counts did not differ significantly between the two groups(MD=12.37,95%CI:-6.71 to 31.45,P=0.20 and MD=5.67,95%CI:-3.00 to14.35,P=0.20,respectively).CONCLUSION:The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus,is beneficial and has potential use for improving INR in PLWH.However,large-scale RCTs are required to provide evidence for optimal intervention strategies.
基金Supported by National Science and Technology Major Project of China During the 13th Five-year Plan Period:New Adjuvant Strategies of Traditional Chinese Medicine on Immune Reconstruction for Longterm ART-treated People Living with HIV(2017ZX10205501)Effects of Traditional Chinese Medicine on Intestinal Bacterial Community Structure of AIDS Patients(2017ZX10205501-001-010)National Natural Science Foundation of China:Immune Mechanism of Immunological Non-responders of HIV/AIDS Treated with Traditional Chinese Medicine from Immune Activation and Toll like Receptor Signal Pathway(No.81503571)。
文摘OBJECTIVE:To evaluate the effects of the Wenshen Jianpi recipe(温肾健脾方,WJR)on immune reconstruction and natural killer(NK)cells in immunological non-responders(INRs)of people living with human immunodeficiency virus(HIV)(PLWH)and propose new therapeutic strategies for HIV.METHODS:Based on Traditional Chinese Medicine treatment principle“invigorating Qi and warming Yang in the spleen and kidneys”,WJR combined with antiretroviral therapy(ART)therapy was performed in a randomized,double-blind,placebo-controlled study of 60 patients with non-responders.The randomized process was executed by the Clinical Evaluation Center of China Academy of Chinese Medical Sciences.Sixty patients who met the inclusion criteria obtained random numbers(that is the drug number)was randomly divided into a treatment group and a placebo control group according to a 1∶1 ratio.CD4+T cell counts and natural killer(NK)cells counts were evaluated at baseline and 12-week,24-week follow-ups.RESULTS:Four participants received random numbers and did not enter the group due to the patient’s own reasons.A total of 56 patients were enrolled,including 28 in the treatment group and 28 in the control group.CD4+T cell counts in the treatment group were significantly increased at week 24(P=0.01<0.05),which were significantly higher than those in the control group(P=0.01<0.05).Although no significant differences were observed between two groups,the CD56bri CD16-NK cell counts in the treatment group were significantly increased after duration.and CD56dim CD16+NK cell counts in the treatment group were significantly higher than those in the control group after 24 weeks of treatment(P=0.025<0.05).As compared with the control group,the treatment group had significantly lower CD56neg CD16+NK cell counts after 24 weeks of treatment(P=0.023<0.05).CONCLUSIONS:WJR promotes the immune reconstruction of INRs and redistribution of NK cell subsets,notably decreasing CD56neg CD16+NK cell counts in INRs.However,the redistribution of NK cell subsets is not beneficial for immune reconstruction in INRs.Further large-scale RCTs are required to evaluate the effect of WJR on immune recovery in INRs and decipher the underlying mechanism.
基金funded by Department of Medicine, University of Udine (Udine, Italy) in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)
文摘AIM To compare high-resolution computed tomography(HRCT) findings between humoral primary immunodeficiencies(hPIDs) subtypes; to correlate these findings to pulmonary function tests(PFTs).METHODS We retrospectively identified 52 consecutive adult patients with hPIDs who underwent 64-row HRCT and PFTs at the time of diagnosis. On a per-patient basis, an experienced radiologist recorded airway abnormalities(bronchiectasis,airway wall thickening, mucus plugging, tree-in-bud, and air-trapping) and parenchymal-interstitial abnormalities(consolidations, ground-glass opacities,linear and/or irregular opacities, nodules, and bullae/cysts) found on HRCT.The chi-square test was performed to compare the prevalence of each abnormality among patients with different subtypes of hPIDs. Overall logistic regression analysis was performed to assess whether HRCT findings predicted obstructive and/or restrictive PFTs results(absent-to-mild vs moderate-tosevere).RESULTS Thirty-eight of the 52 patients with hPIDs showed common variable immunodeficiency disorders(CVID), while the remaining 14 had CVID-like conditions(i.e., 11 had isolated IgG subclass deficiencies and 3 had selective IgA deficiencies). The prevalence of most HRCT abnormalities was not significantly different between CVID and CVID-like patients(P > 0.05), except for linear and/or irregular opacities(prevalence of 31.6% in the CVID group and 0 in the CVID-like group; P = 0.0427). Airway wall thickening was the most frequent HRCT abnormality found in both CVID and CVID-like patients(71% of cases in both groups). The presence of tree-in-bud abnormalities was an independent predictor of moderate-to-severe obstructive defects at PFTs(Odds Ratio, OR, of 18.75, P < 0.05), while the presence of linear and/or irregular opacities was an independent predictor of restrictive defects at PFTs(OR = 13.00; P < 0.05).CONCLUSION CVID and CVID-like patients showed similar HRCT findings. Tree-in-bud and linear and/or irregular opacities predicted higher risks of, respectively,obstructive and restrictive defects at PFTs.
