1.A Twenty Four Week Clinical Trial Using Didonosine, Stavudine and Nevirapine for Highly Active Antiretrioviral Therapy
Huaying ZHOU ; Yuhuang ZHENG ; Xu YANG
Journal of Chinese Physician 2000;0(12):-
Objective To obserre antiviral effect, immune rebuilding efficacy and side effects of didonosine, stavudine and nevirapine combination therapy for human immunodeficiency virus (HIV) type 1 infection. Methods Three medicines were administered for 8 HIV-1 infected cases. Plasma HIV RNA load, and the levels of CD 4 + T cell and CD 8 + T cell were detected before starting treatment and 4,12 and 24 weeks after starting treatment. Side effects and changes in laboratory's examinations were observed during the trial. Results After 12 and 24 week treatment, the plasma HIV-1 level reduced 2 28 logs and 2 63 logs, from a mean baseline of (283,125?187,217) copies/ml to (1,501?930) copies/ml and (669?477) copies/ml, the CD 4 + T cell counts increased from a mean baseline of (337?221) cells/ml to (393?301) cells/ml and (414?284) cells/ml, and CD 8 + T cell counts decreased from a mean baseline of (918?371) cells/ml to (823?315) cells/ml (812?305) cells/ml, respectively. Part of cases occurred mild or medium rash, nausea, headache, fatique, abdomina1 pain and diarrhea, and had blood transaminase increased, and leucocyte and hemoglobin decreased. Conclusions Didonosine, stavudine and nevirapine showed high anti-HIV and immune rebuilding effects in highly active antiretroviral therapy (HAART). The medicine regimen was well tolerated in a six-month clinical trial.
2.Immune reconstitution inflammatory syndrome and its risk factors in highly active antiretroviral therapy
Guoqiang ZHOU ; Min WANG ; Yuhuang ZHENG ; Meng LIU ; Gang XIAO
Chinese Journal of Clinical Infectious Diseases 2010;03(4):213-216
Objective To determine the incidence, clinical manifestation and risk factors of immune reconstitution inflammatory syndromes (IRIS) in highly active antirctroviral therapy (HAART) for HIV/AIDS patients. Methods Two hundred and twelve HIV/AIDS patients received HAART, and were followed up for 6 months. The incidence time and disease spectrum of IRIS were observed. Multiple logistic regression analysis was performed to identify the risk factors for IRIS. Results Among 212 patients, there were 59 (27.8%) experienced an IRIS event during the first 6 months of HAART, 2 of which died (2/59,3.39% ). Median time of IRIS onset was 21 days form HAART initiation. The disease spectrum included tuberculosis, herpes virus infections, pneumocystis jirovecii pneumonia, cryptococcal meningitis and penicillium marneffei infection. Risk factors of IRIS included baseline infections ( OR = 1. 655, P =0.010),fever during HAART ( OR = 2. 344, P= 0.006), and baseline CD4 + count ( OR = 1. 556, P = 0. 034).Conclusions IRIS usually occurred within the first month from HAART initiation, and tuberculosis and herpes virus infection are most common. The occurrence of IRIS is associated with the antigens burden and the decreased baseline CD4 + count.
3.The study on clinical manifestations and T lyphokine levels of HAART associated immune reconstitution inflammatory syndrome
Guoqiang ZHOU ; Yuhuang ZHENG ; Meng LIU ; Min WANG ; Gang XIAO ; Yan HE ; Huaying ZHOU ; Zi CHEN
Journal of Chinese Physician 2010;12(9):1158-1161
Objective To determine the incidence, clinical manifestation and part of lymphokines which represent the balance of Th1 and Th2 in the role of the immunologic mechanisms for IRIS(immune restoration inflammatory syndromes)in patients initiating HAART(Highly Active Antiretroviral Therapy).Methods A prospective study of all patients initiating HAART was performed. A period of six months tracking initiating HAART was performed. The incidence of IRIS, time of occurrence and clinical disease spectrum were recorded. The main T lymphokines including IL-2, INF-γ, IL-4, IL-10 which on behalf of the balance of Th1 and Th2 were detected. To explore the immunopathologic mechanisms for IRIS, the levels of T lymphokines at pre-HAART, initiating HAART for 1 month, 3months and 6 months were compared in IRIS group and non-IRIS group, healthy group. Results A total of 212 patients were enrolled in this study. 59 patients were diagnosed as IRIS at a median of 21 days after HAART initiation (QR 19 days).The main disease spectrum included tuberculosis, herpes virus infections, pneumocystis jirovecii pneumonia. No matter in the IRIS group or non-IRIS group, the main lymphokines baseline of IL-2, INF-γ reduced and IL-4, IL-10 increased before HAART compared to healthy group (P < 0. 05), which had the tendency to restore balance relations initiating HAART. The lymphokines levels had significant difference between baseline and 6 months initiating HAART (P < 0. 05). The changed levels of lymphokines between IRIS group and non-IRIS group before HAART had significant difference compared to healthy group. IL-2, INF-γ increased level[(11.68 ± 2. 89) pg/ml vs (8.52 ±2.26) pg/ml; (22. 19 ± 6. 22) pg/ml vs (18.34 ±5. 35) pg/ml] and IL-10 decreased level [(19. 21 ± 4. 03) pg/ml vs (23. 19 ± 5.92) pg/ml] had significant difference between IRIS group and non-IRIS group initiating HAART I month(P <0. 05). Conclusions The incidence of IRIS during 6 months initiating HAART in HIV/AIDS was 27. 8%, IRIS usually occurred in 1 month initiating HAART. The most common disease spectrum was infectious disease, including tuberculosis and herpes virus infection. Lymphokine of Th1 and Th2 existed unbalance in IRIS group and non-IRIS group before HAART. The unbalance tendency in IRIS group was more obvious. All lymphokines had the trend to recover balance. IL-2, INF-γ significantly increased and IL-10 significantly decreased, which might involve the occurrence of the IRIS.
4.IL-21 level in Chinese HIV infected individuals and its dynamics undergoing HAART
Liwen ZHENG ; Mamadou DIALLO ; Xia CHEN ; Yuhuang ZHENG ; Yan HE ; Huaying ZHOU ; Zi CHEN ; Yan LUO
Journal of Central South University(Medical Sciences) 2011;36(11):1059-1064
To investigate the dynamics of interleukin-21 (IL-21) cytokine in the Chinese HIV patients undergoing highly active antiretroviral therapy (HAAPT).Methods A total of 25 adults with chronic HIV infections,responding to combined highly active antiretroviral therapy (HAART) guideline criteria were enrolled for a 1-year follow-up.After signing an informed consent,20 mL blood was collected from each patient at the base line,6 month and 12 month,respectively.CD4 and CD8 cell count was quantified by flux cytometry,serum HIV RNA quantified by real time PCR and IL-21 concentrations by ELISA.Results IL-21 levels increased gradually during the follow-up but did not reach the healthy levels.IL-21 correlated positively with the CD4 cells but not with CD8 T cells.HIV RNA correlated negatively with CD4 cell count but did not show any relationship with the CD8 cells.Conclusion IL-21 has potential role in the immunopathogenesis of HIV,and might be an important factor in immune construction during HAART.
5.Prospect of IL-2, IL-7, IL-15 and IL-21 for HIV immune-based therapy
Mamadou DIALLO ; Yuhuang ZHENG ; Xia CHEN ; Yan HE ; Huaying ZHOU ; Zi CHEN
Journal of Central South University(Medical Sciences) 2011;36(11):1037-1045
Although highly active antiretroviral therapy (HAART) can effectively reduce the HIV replication,complete recovery of CD4+ T cells does not always occur,even among patients with high virological control.Current researches on γ-chain cytokines have understood the biology and their crucial roles in initiating,maintaining,and regulating the immunologic homeostasis and the inflammatory processes.Due to the multiple functions such as the regulatory and effector cellular function in healthy and disease state,these molecules,their receptors,and their signal transduction pathways are promising candidates for therapeutic interference.The common γ-chain cytokines IL-2,IL-7,IL-15,and IL-21 are primary regulators of T cell homeostasis and thus have been considered prime immunotherapeutic candidates,both for increasing T cell levels/function and augmenting vaccine-elicited viral-specific T cell responses in immunocompromised AIDS patients.The objective of this review is to update the role of the common γ-chain cytokines IL-2,IL-7,IL-15,and IL-21 in HIV AIDS pathogenesis.
6.Regulatory effects of IFN-γ on Treg cells from HIV/AIDS patients receiving HAART for one year
Quan ZHANG ; Yunhai YAO ; Yan HE ; Quan ZHOU ; Yuhuang ZHENG ; Si ZENG
Chinese Journal of Microbiology and Immunology 2014;34(1):15-18
Objective To investigate the regulatory effects of IFN-γon Treg cells from HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) for one year.Methods Thirty HIV/A1DS patients whose CD4+T cells were below 350/μ1 were recruited for HAART therapy.Blood samples were collected at the time points of 0,24,48 weeks after HAART.PBMCs were isolated and randomly divided into two culture groups.One group was cultured directly in medium and another group was co-cultured with IFN-γ (40 pg/ml).The supernatants and cells were separated after 5 days of culture for analysis.The concentrations of IL-12 and CD4+CD25+Foxp3 Treg cells were measured by ELISA and flow cytometry,respectively.Results The levels of IL-12 in the supernatants from the culture without IFN-γ at time points of 0,24,48 weeks after HAART were lower than those from the co-cultured group [(37.02±12.76) vs (41.79± 15.02),t=2.336,P=0.03; (41.76±17.01) vs (47.2±14.26),t=2.702,P=0.014; (48.01± 11.84) vs (53.44± 11.30),t =3.14,P =0.003].The percentages of CD4+ CD25 + Foxp3 Treg cells in CD4+ T cells from the direct-cultured group were higher than those from the co-cultured group at the three time points [(10.41±1.10)% vs (2.40±1.11)%,t=13.89,P=0.000; (8.33±2.03)% vs (1.99± 0.86)%,t=12.93,P=0.000; (5.65±1.55)% vs (1.32±0.73)%,t=10.61,P=0.000].Moreover,the results within the same group at the time points of 0,24,48 weeks upon HAART were also significantly different.Conclusion With the interference of HAART,IL-12 levels were increased,while CD4+CD25+ Foxp3 Treg cells were decreased in patients with HIV/AIDS.IFN-γ plays an important role in this process.
7.Application and obstacles of ANAMMOX process.
Jin RENCUN ; Zhengzhe ZHANG ; Yuxin JI ; Hui CHEN ; Qiong GUO ; Yuhuang ZHOU ; Conghui WU ; Rencun JIN
Chinese Journal of Biotechnology 2014;30(12):1804-1816
Anaerobic ammonium oxidation (ANAMMOX), as its essential advantages of high efficiency and low cost, is a promising novel biological nitrogen elimination process with attractive application prospects. Over the past two decades, many processes based on the ANAMMOX reaction have been continuously studied and applied to practical engineering, with the perspective of reaching 100 full-scale installations in operation worldwide by 2014. Our review summarizes various forms of ANAMMOX processes, including partial nitritation-ANAMMOX, completely autotrophic nitrogen removal over nitrite, oxygen limited autotrophic nitrification and denitrification, denitrifying ammonium oxidation, aerobic deammonification, simultaneous partial nitrification, ANAMMOX and denitrification, single-stage nitrogen removal using ANAMMOX and partial nitritation. We also compare the operating conditions for one-stage and two-stage processes and summarize the obstacles and countermeasures in engineering application of ANAMMOX systems, such as moving bed biofilm reactor, sequencing batch reactor and granular sludge reactor. Finally, we discuss the future research and application direction, which should focus on the optimization of operating conditions and applicability of the process to the actual wastewater, especially on automated control and the impact of special wastewater composition on process performance.
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Bioreactors
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Denitrification
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Nitrification
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Nitrites
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chemistry
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chemistry
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Oxygen
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chemistry
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chemistry
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Waste Disposal, Fluid
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chemistry
8.The changes of Th17, Tr cells and IL-17 in the process of antiviral treatment of Hunan AIDS patients
Jing LI ; Yan HE ; Yuhuang ZHENG ; Huaying ZHOU ; Zi CHEN ; Xia CHEN ; Yan LUO ; Yunhai YAO ; Mei HE
Chinese Journal of Microbiology and Immunology 2011;31(6):512-516
Objective To observe the Th17, IL-17 and Tr cells equilibrium state as well as their changes of HIV infected or AIDS suffered patients in one-year HAART treatment. Methods Select 33 HIV/AIDS patients received HAART treatment while 33 healthy volunteers as controls. Flow cytometry was used to analyze Th17 and Tr cells in venous blood at the time of pre-therapy, 6th, 12th month when IL-17 levels in serum are tested by ELISA. Results The ratio of Th17 cells in CD4 cells in HIV/AIDS patients and volunteers were (1.20±0.37)%, (2.50±1.03)%, (3.70±1.56)%, (4.70±1.43)%, respectively; The ratio of Tr cells were (9.16±3.33)%, (7.19±2.91)%, (5.53±1.88)%, (4.43±0.97)%, respectively; The levels of IL-17 in serum were (5.3±2.5) pg/ml, (7.7±2.4) pg/ml, (10.4±3.1) pg/ml, (17.7±6.6) pg/ml respectively. The Th17 cells' level was positively correlative with the amount of CD4 cells, negatively correlate with the count of viral load. However, the Tr cells level is positively correlative with the count of viral load, negatively relate to the quantity of CD4 cells. Conclusion HIV could make IL-17, Th17 cells and Tr cells lost their balance, but the immune equilibrium state may gradually recover after HAART treatment. Which indicates the IL-17, Th17 cells and Treg cells may play an important role in the pathogenesis of AIDS, and they are likely to be the effective indexes to observe the progress of AIDS and the treatment effect of highly active antiretroviral therapy(HAART).
9.Study on effects of G_2 arrest and apoptosis in Jurkat cell by HTV-1 Vpr
Chun LIU ; Yuhuang ZHENG ; Huaying ZHOU ; Yan HE ; Yongfang JIANG ; Yonghong ZHANG ; Zi CHEN ; Meng LIU ; Xia CHEN ; Liwen ZHENG
Chinese Journal of Microbiology and Immunology 2009;29(11):1025-1030
Objective To explore ability of the vpr gene of human immunodeficiency virus type 1 ( HIV-1 vpr) to induce cell G_2 arrest and apoptosis, and the influence when it mutated, the relationship between Vpr-induced G_2 arrest and apoptosis inductions. Methods Fourteen mutant vpr fragments selected from Chinese patients with HIV. Both eukaryotic expression vector pcDNA3.1( + ) and PCR products purified, double-cut by Hind Ⅲ and BamH Ⅰ and the cut products legated and transformed into competent cells JM109. The 14 reconstructed plasmids electronically transfected into Jurkat-cells, and established cells with pcDNA3. 1-vpr , pcDNA3. 1-vpr-Fs and pcDNA3. 1 blank cells, and without pcDNA3. 1 cell. Cells were harvested after 24 h. mRNA expression was detected by RT-PCR, the DNA content and percentage of apoptosis were monitored by flow cytometry. Results Transfected with 14 mutant HIV-1 Vpr protein, cells display different G_2 percentage and apoptosis ratio. HIV-1 vpr induce cell cycle G_2 arrest and apoptosis, wherase Vpr Fs with a C-terminal end truncation, vector pcDNA3.1( + ) and the blank cells can not. The G_2 percentage and apoptosis ratio reduced when transfected with vpr expressing mutating of 70V, 85P, 86G, 94G compared to the wild type. Subtype AE has a weaker potential to induce cell cycle G_2 arrest and apoptosis. Preliminary, we find that the higher G_2 percentage followed the higher ratio of apoptosis. Conclusion HIV-1 vpr can induce cell cycle G_2 arrest and apoptosis, wherase Vpr Fs with a C-terminal end truncation can not. We firstly found that mutated sites of 70V, 85P, 86G, 94G may reduce the ability of Vpr to induce cell cycle G_2 arrest and apoptosis, subtype AE of vpr in Chinese HIV-1 patients has a weaker potential to induce cell cycle G_2 arrest and apoptosis. Analysis of various mutations in the vpr gene revealed that the extent of Vpr-induced G_2 arrest correlated with the levels of apoptosis. And investigate the pathegenesis of HIV vpr. This can also make a good foundation for further study on gene therapy.
10.Dynamics of IL-2 and IL-7 levels during Highly active antiretroviral therapy and their significance
Ma DIALLO ; Xia CHEN ; Yuhuang ZHENG ; Yah HE ; Bo HE ; Huaying ZHOU ; Zi CHEN ; Yan LUO ; Si ZENG
Journal of Chinese Physician 2012;14(3):308-312,317
Objective The objective of this study was to investigate the course of certain common gamma cytokines ( IL-2 and IL-7 ) and their role on the control of the viral infection in a short term antiviral therapy.Methods A total of 35 adults with chronic HIV infection,responding to combined antiretroviral therapy (cART) guideline criteria were enrolled in this one year follow-up study.After signing an informed consent,20 ml blood were collected from each patient at base line,week 0,week 24 and week 48.1 ml serum collected from each patient was kept at -80 * C until use.Serum concentration of IL-2 and IL-7 was determined using ELISA kit from ebioscience Beijing.CD4 and CD8 cells were counted and quantified using flux cytometry,and serum HIV RNA was quantified using real time PCR.Results All patients had a mean baseline IL-2 level [ (9.67 ± 2.6 ) pg/ml ]lower than the controls [ ( 27.36 ± 5.05 ) pg/ml ].After treatment for 48 weeks,IL-2 increased[ ( 19.8 ± 3.3 ) pg/ml ].However,the mean baseline 1L-7 [ ( 81.74± 20.47 ) pg/ml ]in patients was higher than controls [ ( 2.06 ± 1.52 ) pg/ml ].After treatment for 48 weeks,IL-7 decreased [ (8.36 ± 2.16)pg/ml ].IL-2 showed a significant increase and positive correlation with CD4 cells after HAART initiation (0week:R =0.21,P =0.063,24week:R =0.24,P =0.033,48week:R =0.19,P =0.103; IL-7 showed a significant decrease after HAART initiation but it did not show correlation with CD4 cells.We noted there was a negative correlation between IL-2 and CD4 count in HAART baseline (R =0.28,P =0.012 ),but no correlation between IL-7 and CD4 count from 6 month after HAART.IL-2 showed negative correlation with HIV RNA ( R =- 0.17,P =0.032),but IL-7 showed a relationship with the HIV RNA Conclusions The increase of IL-2 coupled with the decrease of IL-7 revealed a partial restoration of immune response during HAART.However,the absence of relationship with HIV RNA suggested that these cytokines might not be directly involved in the reduction of viral load.