Research progress in role of programmed cell death-1 on HIV infection, prevention and treatment / 中华微生物学和免疫学杂志

Programmed death-1 (PD-1) is an immunosuppressive molecule on the surface of several cells, and functions as a negative regulatory factor in cellular and humoral immune responses via interaction with its ligand PD-L1 or PD-L2. The expression of PD-1 on the peripheral blood lymphocytes of human immunodeficiency virus (HIV) infected people is commonly up-regulated, which not only affects the susceptibility of the virus to target cells and the host′s antiviral immune response, but also affects the effect of antiretroviral therapy. In vitro blocking PD-1/PD-L pathway showed improved HIV-specific immune response of host cells, and PD-1 blockade and/or PD-L1 blockade have been used as an auxiliary means to enhance the efficacy of antiviral therapy and HIV vaccines. This article reviews the progress of the studies on PD-1 in HIV infection, prevention and treatment.

Early Kinetics of Procalcitonin in Predicting Surgical Outcomes in Type A Aortic Dissection Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In cardiac surgery, elevation of procalcitonin (PCT) could be observed postoperatively in the absence of any evidence of infection and also seems to be a prognostic marker. PCT levels measured in patients undergoing Type A aortic dissection (TAAD) were used to determine prognostic values for complications and surgical outcomes.</p><p><b>METHODS</b>Measurements of PCT, C-reactive protein (CRP), and leukocyte count were observed in TAAD surgery patients (n = 251; average age: 49.02 ± 12.83 years; 78.5% male) at presurgery (T0) and 24 h (T1), 48 h (T2), and 7 days (T3) postsurgery. PCT clearance (PCTc) on days 2 and 7 was calculated: (PCTday1- PCTday2/day7)/PCTday1 × 100%. Endotracheal intubation duration, length of stay (LOS) in the Intensive Care Unit (ICU)/hospital, and complications were recorded.</p><p><b>RESULTS</b>PCT peaked 24 h postsurgery (median 2.73 ng/ml) before decreasing. Correlation existed between PCT levels at T1 and duration of cardiopulmonary bypass (P = 0.001, r = 0.278). Serum PCT concentrations were significantly higher in nonsurvivor and multiple organ dysfunction syndrome groups on all postoperative days. PCT levels at T1 correlated with length of time of ventilation support and ICU/hospital LOS. Comparing PCT values of survivors versus nonsurvivors, a PCT cutoff level of 5.86 ng/ml at T2 had high sensitivity (70.6%) and specificity (74.3%) in predicting in-hospital death. PCTc-day 2 and 7 were significantly higher in survivor compared with nonsurvivor patients (38% vs. 8%, P= 0.012, 83% vs. -39%, P< 0.001). A PCTc-day 7 cutoff point of 48.7% predicted survival with high sensitivity (77.8%) and specificity (81.8%).</p><p><b>CONCLUSIONS</b>PCT level and PCTc after TAAD surgery might serve as early prognostic markers to predict postoperative outcome. PCT measurement may help identify high-risk patients.</p>

Reply: The Characteristics about Our Study in Irritable Bowel Syndrome

No abstract available.

The Clinical Application Status and Development Trends of Hydrogen Peroxide Low Temperature Plasma Sterilizers / 中国医疗器械杂志

The hydrogen peroxide low temperature plasma sterilization technology solved the problems of thermo-sensitive materials' disinfection and sterilization based on its development and unique characteristics. This paper introduced the researches of clinical application quality control, and showed the hydrogen peroxide low temperature plasma sterilizers were being widely used in hospitals and highly recognized. According to the clinical data and the literatures of the domestic equipment in preliminary application, it could be concluded that the technology maturity of domestic hydrogen peroxide low temperature plasma sterilizers was in a high level. The advantages of using domestic hydrogen peroxide low temperature plasma sterilizers to do disinfection and sterilization included lower cost, safer, faster and non-toxic, etc. Also the management system should be improved and the clinical staff should master the technical essentials, obey the procedures strictly, verify periodically and offer full monitoring to upgrade the quality of sterilization.

Application of vaseline gauze and cotton piece in eye protection during otological surgery / 现代临床护理

Objective To explore the effects of vaseline gauze combined with brain cotton piece on eye protection during otological surgery . Methods From January to March in 2015 , 80 patients with otological surgery were set as the experiment group , where vaseline gauze and brain cotton piece were used to protect eyes . From October 2014 to December 2014 , another 80 patients with otological surgery were set as the control group , where aureomycin eye ointment was used for eye protection . The two groups were compared in terms of complications incidence . Result The complication incidence of the experiment group was significantly lower than that of control group ( P < 0 . 01 ) . Conclusion Vaseline gauze and brain cotton piece can effectively protect the eyes for patients undergoing otological surgery , lower the occurrence rate of fewer complications and improve patients′comfort .

Association between Diet and Lifestyle Habits and Irritable Bowel Syndrome: A Case-Control Study

BACKGROUND/AIMS: Recent papers have highlighted the role of diet and lifestyle habits in irritable bowel syndrome (IBS), but very few population-based studies have evaluated this association in developing countries. The aim of this study was to evaluate the association between diet and lifestyle habits and IBS. METHODS: A food frequency and lifestyle habits questionnaire was used to record the diet and lifestyle habits of 78 IBS subjects and 79 healthy subjects. Cross-tabulation analysis and logistic regression were used to reveal any association among lifestyle habits, eating habits, food consumption frequency, and other associated conditions. RESULTS: The results from logistic regression analysis indicated that IBS was associated with irregular eating (odds ratio [OR], 3.257), physical inactivity (OR, 3.588), and good quality sleep (OR, 0.132). IBS subjects ate fruit (OR, 3.082) vegetables (OR, 3.778), and legumes (OR, 2.111) and drank tea (OR, 2.221) significantly more frequently than the control subjects. After adjusting for age and sex, irregular eating (OR, 3.963), physical inactivity (OR, 6.297), eating vegetables (OR, 7.904), legumes (OR, 2.674), drinking tea (OR, 3.421) and good quality sleep (OR, 0.054) were independent predictors of IBS. CONCLUSIONS: This study reveals a possible association between diet and lifestyle habits and IBS.

Application of Onodera prognostic nutrition index in prognostic evaluation of elderly patients with colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the applied valuation of Onodera prognostic nutrition index (Onodera index) in elderly patients with colorectal cancer.</p><p><b>METHODS</b>Onodera indexes of 163 elderly patients with colorectal cancer were calculated and these patients were divided into better-nourished group (Onodera index ≥45) and under-nourished group (Onodera index <45). Correlations of Onodera index with general data, operation type, postoperative complication, recovery of gastrointestinal function, clinicopathological feature and prognosis were analyzed. Cox proportional hazards model was also established to identify the independent prognostic factors for prognosis of elderly patients with colorectal cancer.</p><p><b>RESULTS</b>Patients in better-nourished group had significantly higher radical resection rate [90.9% (70/77) vs. 62.8% (54/86), P<0.01], lower postoperative complication rate [17.1% (12/70) vs. 53.7% (29/54), P<0.01] and earlier postoperative defecation [(3.09±1.14) d vs. (3.43±1.98) d, P<0.05] than those in under-nourished group. Onodera index was found to be related to age, tumor location, tumor size, and operation type (all P<0.05). Better-nourished group had significantly better survival than worse-nourished group (5-year survival rate: 64% vs. 24%, P<0.01). Onodera index was identified as an independent prognostic factor for elderly patients with colorectal cancer (RR=0.888, 95%CI:0.800-0.985, P=0.025).</p><p><b>CONCLUSION</b>Onodera index is a valuable clinical marker in preoperative estimation as well as prognosis prediction for elderly patients with colorectal cancer.</p>

Efficacy analysis on the treatment of diabetic nephropathy with Shengqidihuang decoction combined with metformin / 国际中医中药杂志

Objective To observe the clinical effect of treating diabetic nephropathy with Shengqidihuang decoction combined with metformin. Methods 54 cases with diabetic nephropathy were randomly divided into two groups by means of random number table. Both groups were given diabetic routine treatment. The control group was treated with metformin, 0.25 mg each time, three times a day, based on the diabetic routine treatment for 8 weeks, and the treatment group was treated with Shengqidihuang decoction, once a day, 4 weeks as a course, continuously treated for 2 courses based on the control group. 24 h urinary protein (24hUAE) , serum creatinine (SCr) , blood urea nitrogen (BUN) and fasting blood glucose (FBG) were detected before and after the treatment. The clinical effect was observed between the two groups after the treatment. Results The total effective rate of the treatment group and the control group was 85.2% and 66.7% respectively, showing a significant difference (λ2=3.376, P<0.05). Compared with the control group, 24 hUA ,SCr, BUN and FBG in the treatment group decreased significantly (λ2=4.231, P<0.05) after the treatment.24hUAE, SCr, BUN and FBG decreased significantly after the treatment, especially in the treatment group, also showing a significant difference (λ2= 3.754, P<0.05). Conclusion The therapy of mefformin combined with Shengqidihuang decoction on diabetic nephropathy was better than metformin only.

Studying on the prevalence and mutation pattern of N348I which related to the resistance of HIV-1 / 中华流行病学杂志

Objective To elucidate the prevalence and the mutation pattern of N348I that related to the resistance seen in the AIDS patients, in China. Methods Partial pol gene of HIV-1 comprising of full protease (PR) and reverse transeriptase (RT) was obtained from plasma samples of therapy-failure individuals (n=614) and therapy-naive individuals (n=619) by using reverse transcription polymerase chain reaction(RT-PCR). 1233 sequences were then submitted to the HIV-1 drug resistance database of the Stanford University to analyze the prevalence and the emergence pattern of N348I. Results The prevalence of N348I was 6.5％ in the therapy-failure patients and 0.8％ in the naive individuals, respectively. The prevalence of N348I was more popular among those patients whose ART regimens containing zidovudine (AZT or ZDV) than those without AZT in regimens( 14.1％ vs. 4.7％, x2=10.21, P＜0.01 ). N3481 always emerged, and combined with others mutations among patients of ART, whose frequencies were: 85.0％ in combination with thymidine analog mutations (TAMs) and 52.5％ with M184V/I, respectively. Conclusion N348I was somehow prevalent in the therapy-failure patients when using the first-line antiretroviral drugs,and it emerged as unique patterns. This study laid the ground in improving the techaology of drug resistance genotypes detection and providing theoretical basis to study the mechanism of resistance and the law of molecular evolution.

Screening program on novel drug resistance mutations of subtype B' in human immunodeficiency virus type 1 in China / 中华流行病学杂志

Objective To screen the level of novel drug resistance mutations in subtype B' in China. Methods 451 pol sequences collected from the previous study, which including 354 AIDS patients who had received antiretroviral treatment(ART)and 97 the untreated patients. Entire protease gene(codous 1-99)and full-length reverse transcriptase gene(codons 1-560)were included.Variation of mutations between the treated and the untreated patients with consensus/ancestral sequences were compared and the mutations with higher frequencies in the treated patients than in the untreated patients were screened before submitting the mutations to the Stanford HIV Drug Resistance Database(SHDB)(http://hivdb.stanford.edu/). Relation between the mutations and resistance preliminarily was then analyzed, according to the information including SHDB. Results Frequencies of 7 mutations at 6 positions, DI23E, V292I, K366R, T369A, T369V, A371V and 1375V, 2 at DNA polymerase domain and 5 at connection domain of reverse transcriptase(RT)were higher in the treated patients than in the untreated patients. The information of 7 mutations including the SHDB showed that 7 mutations were major variants at corresponding positions, and theirs frequencies were higher in the treated patients using some drugs, than in the untreated patients. Conclusion 7mutations being screened from the China subtype B were possibly associated with the resistance,which called for the construction of mutated viruses by site-directed mutagenesis to identify their effects on the susceptivity of different drugs.

Antiviral effect of lamivudine on HIV-1 targeting MT2 cells influenced by morphine / 中华流行病学杂志

Objective To determine whether morphine having the ability to influence the antiviral effect of lamivudine(3TC)in vitro study.Methods MT2 cells were randomly assigned into morphine+3TC treatment group,morphine+naloxone+3TC treatment group,naloxone+3TC treatment group.Both 3TC and virus control groups were set up.The corresponding MT2 cells were treated with opiates antagonist(naloxone)for 0.5 hours before the 24-hours morphine treatment program was implemented while all of the groups were then infected with equal amounts of cell-free HIV-1 ⅢB strain and 3TC.HIV-1 p24 antigen in culture supernatants collected at days 3,4,5 and 6after infection status was tested and the inhibition of 3TC anti-HIV-1 p24 antigen of various treatment groups calculated.Results Inhibition of 3TC anti-HIV-1 p24 antigen of Morphine+3TC treatment group was the lowest when HIV-1 infected cells at 3rd and 4th day and showed significant difierence (P<0.05)when compared to the 3TC control.However,there was no statistically significant difference among them(P>0.05),when virus was infected the cells at 5th and 6th day.The difference of 3TC anti-HIV-1 p24 antigen inhibition between the morphine+naloxone+3TC treatment group and the naloxone+3TC treatment group was not significant(P>0.05).Similar results were obtained when these two groups were compared to the 3TC control group(P>0.05),respectively.The 3TC anti-HIV-1 p24 antigen inhibition of each treatment group reduced as the time of infection prolonged,showing a significant and time-course effbct.Conclusion The 3TC antiviral effect was reduced by morphine in the early stage of infection,and could be blocked by naloxone.

Allele-specific real-time PCR testing for minor HIV-1 drug resistance mutations: assay preparation and application to reveal dynamic of mutations in vivo / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is very important for the clinical management to test for minor HIV-1 resistance mutations accurately and sensitively. The conventional genotypic assays of HIV drug resistance detection based on sequencing can only discriminate the mutations which present in more than 20% - 30%. The aim of this study was to evaluate allele-specific real-time PCR (ASPCR) to detect the resistance-related mutations located at positions 103, 184 and 215.</p><p><b>METHODS</b>We developed the allele-specific PCR assay, using the most common drug resistance mutations in Chinese AIDS patients, K103N, M184V/I, T215F/Y as a model system. The standards were constructed by cloning the wild-type and mutant DNA fragments into the T-vector. We designed specific primers to discriminate mutant templates in the real-time PCR using SYBR green as a fluorescence reporter. And then we evaluated the ASPCR assay and tested 140 clinical samples using this method.</p><p><b>RESULTS</b>The sensitivities of ASPCR assay were 0.04% for K103N, 0.30% for M184I, 0.40% for M184V, 0.03% for T215F and 0.02% for T215Y. The intra-assay and inter-assay coefficients of variation were less than 0.42. One hundred and forty plasma samples were tested by ASPCR and dynamic resistance curves of ten patients were obtained.</p><p><b>CONCLUSIONS</b>Drug resistance emerged half a year after the start of antiretroviral therapy. The mutation of T215Y emerged 1 to 1.5 years after starting treatment and then increased rapidly. The ASPCR assay we developed was a sensitive, accurate and rapid method to detect the minor HIV-1 variants and it can provide earlier and more drug-resistance information for HIV research and AIDS antiretroviral therapy.</p>

In vitro selection and identification of HIV strain which is resistance to two new HIV-1 nonnucleoside reverse transcriptase inhibitors / 药学学报

JB25 and JB26 are new HIV-1 nonnucleoside reverse transcriptase inhibitors, and show potent anti-HIV activities. Sequential passage experiments with wild-type virus were performed to select and identify mutations induced by these two compounds in vitro. For the initial passage, compounds were present at approximately 2-fold IC50 in MT-2 cells. When cytopathic effect (CPE) was observed in more than 75% of the cells, the culture supernatants were collected. For the subsequent passages, fresh MT-2 cells were infected with 1 mL supernatants from the previous passage (regardless of the virus titer) and cultured in the presence of the compounds at concentrations that were increased 2-fold compared with that in the previous passage. This procedure was repeated with increasing concentrations for 12 passages. JB25 had amino acid substitution L100I (TTA-->ATA) at passage 6, and then changed into 100 M (ATA-->ATG) at passage 12, which was rare mutation form and had not been reported. At the same time, Y188C (TAT-->TGT) mutation appeared at passage 10. For JB26, there was a L100I (TTA-->ATA) mutation at passage 10. In a word, JB25 and JB26 showed a low genetic barrier to the development of resistance, and the resistance to JB26 developed slower than JB25. The mutations selected by JB25 and JB26 were mainly associated with codons 188 and 100 of HIV-1 reverse transcriptase.

Subtype and characterization of gag gene of HIV-1 strains prevalent in some areas of China / 军事医学科学院院刊

Objective:To investigate the subtype distribution of HIV-1 strains prevalent in four areas of China,and to study the characteristics of gag gene variation and changes in antigen epitopes under the host immune pressures. Methods:The plasma of HIV-1 infected people from Henan, Guangdong, Sichuan and Beijing in China were collected. Virion RNA was extracted directly from plasma after the virion was condensed. The gag gene was amplified by RT-PCR and nested-PCR.Sequences were subtyped by Genotyping Tool software, and phylogenetic analysis of gag gene were performed using the MEGA 4.1 software.The gene distances intra each subtype were calculated by Distance program. The Ks/Ka ratios were calculated using SNAP program. The variation analysis of CTL antigen epitopes restricted by main HLA-Ⅰ specificities in China was performed.Results:Six subtypes or circulating recombinant forms(CRFs)of HIV-1,including B',CRF07_BC,CRF01_AE,B,CRF08_BC and CRF02_AG,were identified in four areas of China.The gene distances intra each subtype were CRF01_AE>B>CRF08_BC> CRF07_BC>B' listed in order of size, meanwhile the order of Ks/Ka ratios was CRF01_AE>B>CRF08_BC>B'>CRF07_BC. Far more diversity of antigen epitopes in P17 region was observed than that in P24.Epitope mutations intra subtypes were CRF01_AE>B>B'>CRF07_BC listed in order of size. Conclusion:Itseems that CRF01_AE is under the strongest immune pressures,and displays the most diversity of gene and variation of epitopes intra subtypes prevalent in China, followed by subtype B, B' and CRF07_BC. The discrepancy of epitope mutations intra the subtypes is significant.

Anti-human immunodeficiency virus type 1 activity of two new nonnucleoside reverse transcriptase inhibitors in combination with other 3 antiretroviral agents in vitro / 军事医学科学院院刊

Objective:To evaluate the anti-HIV-1 activity of two new nonnucleoside reverse transcriptase inhibitors (NNRTIs), JB25 and JB26, in combination with 3 approved drugs (AZT, EFV, SQV)in vitro.Methods:The serially diluted 10 concentrations of JB25 and JB26 were combined with 7 serially diluted AZT, EFV and SQV respectively.The combination was added to 384 cell culture plates and then cocultured with HIV-1 ⅢB infected MT-2 cells for 3 days. Finally, the HIV-1 production was determined by measuring the expression of reporter genes of TZM bl cells. The data were analyzed by MacSynergy Ⅱ software.Results:The average capacity of synergism/antagonism of JB25 with AZT, EFV and SQV was 244.45/-5.05(nmol/L)~2%, 119.58/-65.93 (nmol/L)~2% and 145.83/-0.32 (nmol/L)~2% respectively;the average capacity of synergism/antagonism of JB26 with AZT, EFV and SQV was 398.90/0(nmol/L)~2%, 103.62/-0.49(nmol/L)~2% and 138.473/-0.27 (nmol/L)~2% respectively. Conclusion:Two new NNRTIs JB25 and JB26 develop synergism when combined with 3 approved drugs, respectively. MacSynergy Ⅱ software could evaluate the anti-HIV-1 activity of drug combination.

The common causes of premature delivery and the analysis of tocolytic effect / 中国基层医药

Objective To investigate the eomman causes of premature delivery,the tocolytic effect and suc-cess ratio and the birth situation of premature infants. Methods 150 pregnant women with natural delivery or iatro-genie preterm labor from 28 weeks to 34 weeks who carried out tocolytic therapy because of threatened preterm labor or premature delivery after tocolytic therapy were selected. The common inducement of premature delivery, the pro-longed gestational weeks, the success ratio of tocolyis and the birth situation of premature infants were retrospectively analyzed. Results The premature rupture of membranes(PROM) ,the spontaneous uterine contraction and iatrogenic preterm labor were the main reasons of premature labor. The primiparas are the majority. The iatrogenic partus pre-maturus were prolonged, the asphyxia rate of premature infants was still high. The incidence of premature rupture of fe-tal menbranes in pregnant with tocolytic therapy beyond 1 week was 3. 3% ,and the incidence of spontaneous urerine contraction was 4. 8%. Conclusion Antenatal care and prenatal diagnosis are important to decrease the premature labor ratio as early as possible to use the D. X. M to promote the fetal lung maturity, so as not to delay the treatment.

Competitive capacity of HIV-1 strains carrying M184I or Y181I drug-resistant mutations / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Virus with nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance. For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine (3TC) or nevirapine (NVP) resistant mutations.</p><p><b>METHODS</b>3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay.</p><p><b>RESULTS</b>3TC-resistant (M184I mutation) and NVP-resistant (Y181I mutation) virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages.</p><p><b>CONCLUSIONS</b>The NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.</p>

Immunogenicities of Env glycoproteins from circulating HIV-1 isolates in China focusing on the strategy of "DNA prime plus protein boost" / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The adenovirus-based HIV-1 vaccine developed by Merck Company suffered from an unexpected failure in September 2007. This generated a big shift in the strategy of HIV vaccine development with renewed focus on the induction of neutralizing antibodies. A major challenge in developing an HIV-1 vaccine is to identify immunogens and adopt delivery methods that can elicit broadly neutralizing antibodies against primary isolates of different genetic subtypes.</p><p><b>METHODS</b>Most circulating HIV-1 isolates in China are composed of clades Thai-B, CRF_BC and CRF01_AE. In order to construct DNA vaccines against these 3 HIV-1 subtypes, DNA vaccines carrying the gp120 regions from HIV-1 isolates of GX48(AE), GX79(AE), NX22(BC), GS22(BC), HN24(Thai-B) were constructed. Expression of gp120 from these DNA vaccines was detected by Western blotting in transiently transfected 293T cells. Pilot immunizations of New Zealand white rabbits were performed using the strategy of "DNA prime plus protein boost" and the neutralizing antibody response was detected in a Tzm-bl cell based assay against different HIV-1 strains.</p><p><b>RESULTS</b>Response of gp120-specific antibody was relatively low after DNA primes (mean titer = 10(4.72)); however, the titer of gp120-specific antibody went up with 2 protein boosts (mean titer = 10(6.81)). Above all, neutralizing antibody (Nab) titers induced by this combined approach were much better than those elicited by DNA or protein used alone (P < 0.01). Neutralizing activities of immunized rabbit sera against several pseudoviruses and laboratorial strains were evaluated, most rabbit sera primed with monovalent vaccine were capable of neutralizing only 1 of 5 viruses, however, sera primed with the polyvalent DNA vaccines were able to neutralize at least 2 of 5 viruses.</p><p><b>CONCLUSION</b>Polyvalent DNA prime plus protein boost is an effective immunization strategy to broaden the neutralization breadth and further research should be performed on the basis of this pilot study.</p>

Study on the difference of the APOBEC3G mRNA levels among HIV long-term nonprogressors, slow progressors, people at high risks and normal people / 中华流行病学杂志

Objective To examine the APOBEC3G(hA3G)mRNA levels of four different groups in the human immunodeficiency virus(HIV)prevalent areas in central China and to analyze the relationship between hA3G mRNA levels and HIV disease progression.Methods We collected peripheral blood and isolated the peripheral boold monouuclear cells(PBMCs),and then cryo-preserved the PBMCs in liquid nitrogen.Prior to the total extraction of RNA,PBMCs were resuscitated and mRNA were reverse Transcripted to cDNA in vitro.Real-time polymerase chain reaction(PCR)was used to test hA3G mRNA levels of different groups.Results There were 13 HIV long term non-progressors with the mean CD+4 T lymphocyte count as(716±169)per μl and the mean affection time as(12.5±2.3)years.There were 48HIV slow progressors with the mean CD+4 T lymphocyte count as(233±144)per μl and the mean affection time as(10.7±2.2)years.The hA3G mRNA level of HIV long term nonprogressors was higher than that of normal people while the hA3G mRNA level of HIV slow progressors was higher than that of normal people and high risk people.There were no correlations between CD+4 T lymphocyte count and hA3G mRNA levels of HIV long term nonprogressors as well as in HIV slow progressors.Conclusion There was difference found in the hA3G mRNA levels of four groups in the HIV popular area in central China while no correlation between CD+4 T lymphocyte count and hA3G mRNA levels of HIV long term nonprogressors as well as in HIV slow progressors were found.

Research on the selective kinetics of HIV-1 nucleoside reverse transcriptase inhibitor drug resistance-associated mutations among 4 AIDS patients receiving highly active antiretroviral therapy / 中华流行病学杂志

<p><b>OBJECTIVE</b>To elucidate the molecular evolutional characteristics of HIV-1 nucleoside reverse transcriptase inhibitor (NRTI) drug resistance-associated mutations in patients with AIDS receiving highly active antiretroviral therapy.</p><p><b>METHODS</b>We selected 4 AIDS patients receiving highly active antiretroviral therapy (HAART) with good adherence under a HIV-1 drug resistance cohort from a rural region in central China. Those people carried susceptible virus at the beginning of treatment and gradually came to produce virus resistant to NRTIs during the process of antiretroviral therapy (ART). Reverse transcriptase (RT) genes from each patient's peripheral blood samples (from 3 to 33 months after withdrawal) were cloned and sequenced in succession.</p><p><b>RESULTS</b>We sequenced a total number of 855 clones and obtained the HIV-1 NRTI drug resistance-associated mutations patterns of the 4 patients. Typical resistance mutations of thymidine analogue mutations (TAMs) pattern 1, such as L210W, T215Y and M41L, were generated in patient 'A'. TAMs pattern 2, including D67N, K70R and K219Q mutations, was discovered in patient 'B'. Interestingly, in patient 'C', some clones comprising not only TAMs pattern 1 mutations (T215Y) but also TAMs pattern 2 mutations (K70R, D67N).</p><p><b>CONCLUSION</b>The four patients show different pathways on HIV-1 NRTI drug resistance-associated mutations, including TAMs pattern 1, TAMs pattern 2 and the fusion pattern of TAMs-1 & TAMs-2. We also noticed that the tendency of gradual accumulation was obvious and those mutations detected earlier tended to be the predominant strains.</p>