1.The development of anti-HIV-1 drugs.
Acta Pharmaceutica Sinica 2010;45(2):165-76
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immunodeficiency disease syndrome (AIDS). After over 26 years of efforts, there is still not a therapeutic cure or an effective vaccine against HIV/AIDS. The clinical management of HIV-1 infected people largely relies on antiretroviral therapy (ART). Although highly active antiretroviral therapy (HAART) has provided an effective way to treat AIDS patients, the huge burden of ART in developing countries, together with the increasing incidence of drug resistant viruses among treated people, calls for continuous efforts for the development of anti-HIV-1 drugs. Currently, four classes of over 30 licensed antiretrovirals (ARVs) and combination regimens of these ARVs are in use clinically including: reverse transcriptase inhibitors (RTIs) (e.g. nucleoside reverse transcriptase inhibitors, NRTIs; and non-nucleoside reverse transcriptase inhibitors, NNRTIs), protease inhibitors (PIs), integrase inhibitors and entry inhibitors (e.g. fusion inhibitors and CCR5 antagonists). Here, we intend to provide updated information of currently available antiretroviral drugs for ART to promote the development of novel anti-HIV-1 drugs.
2.Effect of Tourniquet Modified Strapping on Venipuncture in Tumor Patients
Modern Hospital 2017;17(5):778-780
Objective To investigate the effect of tourniquet modified strapping on venipuncture in tumor patients.Methods 120 tumor patients whose veins were exposed hard in radiotherapy department from October 2016 to March 2017, randomly divided into the control group and the observation group equally.The control group was treated with the traditional single strapping tourniquet to have venipuncture and the observation group with tourniquet modified strapping.Results The venous filling degree, the success rate of first puncture, and the satisfaction of the patients in the observation group were significantly higher than those in the control group (P<0.05).Conclusion The use of tourniquet modified strapping in tumor patients whose veins were exposed hard can significantly improve the venous filling degree, the success rate of puncture, the satisfaction of patients and the quality of nursing service, and thus it is worthy of clinical promotion.
3.Characteristics of CD8+ stem memory T cells in patients with chronic HIV-1 infection during antiretroviral therapy
Xiaofan LU ; Huan XIA ; Bin SU ; Hao WU ; Tong ZHANG
Chinese Journal of Microbiology and Immunology 2017;37(4):250-254
Objective To investigate the characteristics of CD8+ stem memory T cells (CD8+Tscm) in patients with chronic HIV-1 infection before and after antiretroviral therapy (ART) and to analyze their associations with progression of HIV-1 infection.Methods Thirty-six patients with chronic HIV-1 infection and 20 healthy subjects were enrolled in this study.Flow cytometry was performed to detect the percentages and absolute numbers of CD8+Tscm in patients with chronic HIV-1 infection before and after antiretroviral therapy (ART) as well as in healthy subjects.Correlation analysis was used to demonstrate the relationships between CD8+Tscm and markers for progression of HIV-1 infection (CD4+T cell count, HIV-1 viral load and level of activated T cells).Results The percentages and the absolute numbers of CD8+Tscm in patients with chronic HIV-1 infection had no significant change before and after ART.They were respectively positively correlated with the percentages and the absolute numbers of CD4+Tscm.The percentage of CD8+Tscm was proportional to the percentage of CD8+ central memory T cells (CD8+Tcm), but was inversely proportional to the percentage of CD8+ effector memory T cells (CD8+Tem).In addition, the percentages of CD8+Tscm in patients with HIV-1 infection were negatively correlated with the viral loads before ART.Conclusion CD8+Tscm are responsible for maintaining the homeostasis of other CD8+T cell subsets.CD8+Tscm play an important role in inhibiting viral replication.
4.HPLC enantioseparation, absolute configuration determination and anti-HIV-1 activity of (±)-F18 enantiomers.
Leilei ZHANG ; Hai XUE ; Li LI ; Xiaofan LU ; Zhiwei CHEN ; Gang LU
Acta Pharmaceutica Sinica 2015;50(6):733-7
Racemic (±)-F18 (10-chloromethyl-11-demethyl-12-oxo-calanolide A), an analog of nature product (+)-calanolide A, is a new anti-HIV-1 nonnucleoside reverse transcript inhibitor (NNRTI). A successful enantioseparation of (±)-F18 offering (R)-F18 and (S)-F18 was achieved by a chiral stationary phase prepared HPLC. Their absolute configurations were determined by measurement of their electronic circular dichroisms combined with modem quantum-chemical calculations. Further investigation revealed that (R)-F18 and (S)-F18 shared a similar anti-HIV activities, however, (R)-F18 was more potent than (S)-F18 against wild-type virus, K101E mutation and P225H mutation pseudoviruses.
5.Research on methods of continuous blood sampling from caudal vein of rat
Yang WANG ; Xiaofan LU ; Hangjie LI ; Zhaohuan WU ; Ya LI ; Xiaolin SONG
Journal of Regional Anatomy and Operative Surgery 2015;(5):505-507
Objective To continuously draw blood from caudal vein of SD rats which controlled by the homemade holder with an im-proved method, and the effects of this method was evaluated according to the relevant indicators. Methods The 24 SD rats should be drew the blood from the caudal vein by the improved disposable infusion needle and supplied physiological saline at the condition of ether inhala-tion anesthesia and once a day until to the thirteenth day,and then the times of draw blood and the number of survival rats only to calculate the success rate and survival rate of rats were record. Results In the 12 days,the tail vein blood of 24 SD rats were successfully collected. But a rat died of excessive ether inhalation anesthesia on the thirteenth day. The success rate was 99. 68% and the rat survival rate was 95. 83%. Conclusion The method that applying an improved disposable infusion needle and supplying physiological saline is safe and ef-fective,flexible and convenient,which is suitable for experimental study that needs to draw blood from caudal vein of the SD rat at the contin-uous time.
6.Phenotypes and HIV-1-specific T cell responses of KIR3DL1 positive CD8 cells in patients with early HIV-1 infection
Xin ZHANG ; Bin SU ; Xiaofan LU ; Zhiying LIU ; Yunxia JI ; Rui WANG ; Tong ZHANG ; Hao WU
Chinese Journal of Microbiology and Immunology 2016;36(9):699-703
Objective To investigate the phenotypes and the HIV-1-specific T cell responses of KIR3DL1 positive CD8 cells in patients with early HIV-1 infection. Methods Fifty-six HIV-1 antibody negative individuals and thirty-two patients with early HIV-1 infection were enrolled in the study. Fluores-cence-activated cell sorting (FACS) was performed to detect the phenotypes of KIR3DL1 receptor expressed on the surface of CD8 cells. The levels of IFN-γwere measured by intracellular cytokine staining assay after the PBMCs were stimulated with an HIV-1 Gag peptide pool. Results The percentages of KIR3DL1+CD8 T cells in HIV-1 negative individuals and patients with early HIV-1 infection were 1. 45% (0. 12%-8. 4%) and 0. 82% (0. 14%-6. 14%), respectively, and there was no significant difference between them. The percentages of KIR3DL1+CD8 Temra cells in HIV-1 negative individuals and patients with early HIV-1 infec-tion were (4. 55±3. 84)% and (6. 71±8. 50)%, respectively, which were significantly higher than the per-centages of KIR3DL1+CD8 Tem cells, which were (0. 50±0. 59)% and (1. 18±1. 39)%, respectively (all P<0. 01). Moreover, the percentages of KIR3DL1+CD8 Tem cells in patients with early HIV-1 infection were higher than those in HIV-1 negative individuals (P=0. 001 2). The percentage of KIR3DL1+CD8 Temra cells was positively correlated with the HIV-1 viral load in patients with early HIV-1 infection ( rs=0. 576,P=0. 000 9). The percentages of KIR3DL1+CD8 Temra cells in HIV-1 patients, whose viral loads were larger than 4. 0log, were much higher than those in HIV-1 patients with viral loads less than 4. 0 log (P=0. 002). Additionally, the levels of IFN-γsecreted by KIR3DL1 positive CD8 cells were much lesser than those secreted by KIR3DL1 negative CD8 cells (P<0. 000 1). Conclusion The receptor of KIR3DL1 was mainly expressed on CD8 Temra cells in both HIV-1 negative subjects and patients with early HIV-1 infec-tion. High HIV-1 viremia was associated with the high percentage of KIR3DL1+CD8 Temra cells. The KIR3DL1 positive CD8 cells induced lower HIV-1-specific T cell responses.
7.The Clinical Study on Expression of Midkine Gene in Childhood Acute Lymphoblastic Leukemia
Ronghua HU ; Ying LU ; Jianxiang WANG ; Xiaofan ZHU ; Qinghua LI ; Li MA ; Bin LI ; Tianxiang PANG
Tianjin Medical Journal 2009;37(10):817-819
Objective: To investigate the expression of midkine (MK) gene in childhood acute lymphoblastic leukemia (ALL) and the clinical significance of MK thereof. Methods: The real-time PCR was used to assay MK gene expression in bone marrow of 15 normal children and 124 childhood ALL patients, including 73 patients in progression and 51 patients in complete remission. Three stratifications of progressing patients were established by prognostic factors such as white blood cell count, age, immunopherotype and response to the 7-day prednisolone prephase. Results: The significant statistic difference in MK gene expression was found between the progression group, the complete remission group and the normal group (P< 0.01). The MK gene expression was over-expressed in B-ALL than that in normal group. Furthermore, there was statistic difference between B-ALL and T-ALL (P< 0.01). But there was no difference in MK mRNA expression between the normal control and T-ALL. The assay in risk stratifications showed that the levels of MK gene were higher in standard risk group and mid-risk group than that in high risk group (P< 0.01 and P< 0.05, respectively). There was no significant difference between standard risk group and mid -risk group (P = 0.32). No correlations were found between MK level and age, gender or lactate dehydrogenase level in serum. The expression of MK was significantly lower in the group with higher white blood cells(WBC≥ 25×10~9/L) than that with lower WBC (WBC<25×l0~9/L) in peripheral blood (P< 0.05). Conclusion: The high level of MK was a favorable prognostic factor in childhood acute lymphoblastic leukemia patients.
8.Effects of asymptomatic arteriovenous fistula closure on left ventricular morphology and function in renal transplant recipients-a prospective, randomized, controlled study
Wenjia DI ; Hongji YANG ; Yiping LU ; Qing RAN ; Yu ZHANG ; Xiaofan DENG ; Wei XIONG
Chinese Journal of Organ Transplantation 2012;(10):594-597
Objective To evaluate the effects of asymptomatic arteriovenous fistula closure on left ventricular morphology and function in renal transplant recipients.Methods Between March 2007 and March 2011,a total of 60 patients undergoing consecutive kidney transplantation with asymptomatic arteriovenous fistula were divided randomly into two groups: arteriovenous fistula closure group,and non-arteriovenous fistula closure group.By using echocardiography,the changes in CO,CI,EF,LVEDV and LVMI were analyzed.Results At 12th month after transplantation,the values of CO,LVEDV and LVMI were significantly lower than those before transplantation (P<0.05).The value of CI also showed a tendency to decrease (P>0.05),and the value of EF was increased significantly (P<0.05).At 6th month after arteriovenous fistula closure (18 months after transplantation),the values of CO,CI,LVEDV and LVMI were significantly lower than those before arteriovenous fistula closure (12 months after transplantation) (P<0.05),and the value of EF was increased significantly (P<0.05),but the values of CO,CI,EF,LVEDV and LVMI remained unc(b)anged in controls (P>0.05).At 18th month after transplantation,the values of CO (4.4 ±0.8 L/min),CI [3.0 ± 0.8 L·min-1·m-2],LVEDV (110.0 ± 17.4 ml) and LVMI (114.7 ± 42.5g/m2) in trial group were significantly lower than the values [CO: 5.1 ± 0.9 L/min,CI: 3.5 ± 1.0L·min-1·m-2,LVEDV: 121.4±19.3 mL,LVMI: 138.4±44.1 g/m2] in controls (P<0.05),and the value of EF (75.2% ± 7.4% vs.70.5% ± 8.2%) significantly higher (P<005).Conclusion In both groups,kidney transplantation benefits significantly the regression of cardiac mass,cardiac index and left ventricular dimensions,but closure of asymptomatic AVF induces more significant regression.
9.Cytotoxic role of γδT cells to latency cells in patients with early human immunodeficiency virus-1 infection
Zhen LI ; Xiaofan LU ; Jianping SUN ; Bin SU ; Hao WU ; Yonghong ZHANG ; Tong ZHANG
Basic & Clinical Medicine 2017;37(7):953-958
Objective To investigate the cytotoxicity of γδ T cells to HIV-1 latency cells in patients with early HIV-1 infection.Methods Sixteen early HIV-1-infected patients were enrolled in this study.Peripheral blood mononuclear cells (PBMCs) of patients were isolated and γδ T cells were expanded using zoledronate (5 μmol/L) and interleukin (IL)-2 (1 000 IU/mL) ex vivo.Lactic dehydrogenase (LDH) was used to detect the cytotoxic role of γδ T cells to HIV-1 latency cells(J-Lat Full Length Clonel0.6).The phenotype of γδ T cells before and after expansion and the intensity of GFP in HIV-1 latency cells were detected by flow cytometry.Results Zoledronate plus IL-2 stimulated rapid and large γδ T cells proliferation ex vivo (P<0.001).γδ T cells showed high cytotoxici ty to latency cells,and the intensity of GFP in latency cells was decreased significantly (P<0.05).Moreover,expanded γδ T cells displayed cytotoxic NK-like phenotype,the frequency of CD56+ Vδ2 T cells in patients with early HIV-1 infection was significantly higher than that of healthy controls.Conclusions γδ T cell has an ability to eradicate HIV-1 latency,and γδ T cell-based autologous or xenogenous adoptive immunotherapy will have promise prospects to cure HIV-1 infection.
10.Effect of Mitogen-Activated Protein Kinases on Cerebral Ischemia Induced by Photothrombosis in Swedish Amyloid Precursor Protein Transgenic Mice
Liangyu ZOU ; Yiguang RAO ; Wanzhu GU ; Xuejun FU ; Gang LI ; Xiaofan CHU ; Yi LU
Journal of Sun Yat-sen University(Medical Sciences) 2009;30(4):433-436,445
[Objective] To investigate the effect of mitogen-activated protein kinases (MAPK) on cerebral ischemia induced by photothrombosis in Swedish amyloid precursor protein (APP/SWE) transgenic mice.[Methods] In APP/SWE transgenic mice and non-transgenic mice (n = 12,respectively),photothrombotic stroke was induced,on 7 d after cerebral ischemia,the amount of the survival neuron in the penumbra was counted using Nissl staining (n = 6),and the activities of p38MAPK and JNK were measured by Western blot (n = 6).[Results] On 7 d after cerebral ischemia,ratio of amount of survival neuron over the penumbra in hippocampus in the ischemic side to that in the non-ischemic side in the non-transgenic mice group (78.3 ± 1.3)% was significantly higher than that in the APP/SWE transgenic mice group (70.5 ± 1.4)% (P < 0.05);compared with the non-ischemic hemisphere,the activities of p38 MAPK and JNK increased significantly in the ischemic hemisphere in the APP/SWE transgenic mice group (P < 0.05),whereas,there was no significant difference between ischemic and non-ischemic hemisphere in the non-transgenic mice group (P > 0.05).[Conclusion] Photothrombosis causes more severe damage in the APP/SWE transgenic mice group than that in the non-transgenic mice group.The possible mechanism includes the increased activities of MAPK which enhance the process of neuronal cell apoptosis.