Multicenter post-marketing clinical evaluation on the clinical performance of the five domestic fast nucleic acid detection reagents for 2019-nCoV / 中华检验医学杂志

Objective:This multicenter clinical evaluation analyzed the clinical performance of five fast nucleic acid detection systems for 2019-nCoV.Methods:Clinical performance of the five fast nucleic acid detection reagents approved in China was evaluated in the present study. Fifty-seven throat swabs samples from COVID-19 patients and fifteen throat swabs samples from healthy people were collected from the First Affiliated Hospital of Zhejiang University school of Medicine, Tongji Hospital of Tongji Medical College of HUST, and National Institute of Viral Disease Control and Prevention of CDC to evaluate the positive coincidence rate, negative coincidence rate, total coincidence rate, the detection time and retest rate as well as the relation between positive intensity and positive coincidence rate of the five fast nucleic acid detection systems in November 2020.Results:The positive coincidence rates of the five kits were 92.59% (50/54), 83.64% (46/55), 98.25% (56/57), 94.44% (51/54) and 98.18% (54/55); and the negative coincidence rates were 93.33% (14/15), 93.33% (14/15), 86.67% (13/15), 100% (14/14) and 93.33% (14/15); and the total coincidence rates were 92.75% (64/69), 85.71% (60/70), 95.83% (69/72), 94.20% (65/69) and 97.14% (68/70), respectively. The positive coincidence rate of the five kits reached 100% for the strong-positive (90/90) and medium-positive samples (84/84), but only 82.18% (83/101) for weak-positive samples (cycle threshold value>33), and the retest rate of two kits were 15.28% (11/72) and 12.50% (9/72), which were both higher than 10%. Total time from sample extraction to amplification was between 32.33-65.33 minutes for these five kits.Conclusion:The five fast nucleic acid detection reagents have good performance and can be used as a supplement to routine nucleic acid detection reagents.

Latent profile analysis of early rehabilitation exercise compliance in first-episode stroke patients / 中国实用护理杂志

Objective:To explore the different types and characteristics of rehabilitation exercise compliance of patients with first stroke at 2 weeks of onset, and analyze its influencing factors, so as to provide reference for the formulation of targeted health education.Methods:A cross-sectional investigation was conducted in Neurology Department of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June, 2021. 276 patients with first-episode stroke were investigated by the Questionnaire of Exercise Adherence at 2 weeks of the onset. The potential profile analysis was conducted to explore characteristics classification of the rehabilitation exercise compliance. And the chi-square test was used to compare demographic differences among different categories and ordered multi classification Logistic regression was used to explore the influencing factors of rehabilitation exercise compliance.Results:The patients were divided into 109 cases with high rehabilitation exercise compliance (39.5%), 114 cases with moderate rehabilitation exercise compliance (41.3%), and 53 cases with low rehabilitation exercise compliance (19.2%). There were statistically significant differences in education level, consciousness level at admission, complications and limb muscle strength among the three types of patients ( χ2 values were 6.17-31.50, all P<0.05). Ordered multi classification Logistic regression showed that the patient′s education level, the patient′s consciousness level at admission, whether there were complications and limb muscle strength would affect the rehabilitation exercise compliance of stroke patients ( P<0.05). Conclusions:There are three potential categories of rehabilitation exercise compliance in patients with first stroke. Patients with illiteracy, drowsiness, complications and poor limb muscle strength have poor rehabilitation exercise compliance.

Primary drug resistance to integrase inhibitors among newly diagnosed HIV infected patients in Shenyang city / 临床检验杂志

Objective@#To explore the transmission of integrase inhibitors (InIs) resistant strains among newly diagnosed HIV-1 infected individuals in Shenyang city. @*Methods@#Eighty newly diagnosed HIV infected individuals were retrospectively collected in Shenyang from June 2018 to March 2019. The sequences of integrase-encoding genes were amplified from the viral RNA in plasma. The viral genotypes were analyzed with phylogenetic method and the mutations of drug resistance genes were interpreted according to the algorithm of Stanford HIV drug resistance database. The primary drug resistance rates were calculated and natural polymorphisms on InIs resistance sites in different subtypes of the virus strain were analyzed. @*Results@#Among the 80 HIV-1 infected individuals, 51, 14 and 6 cases were genotyped as HIV CRF01_AE, CRF07_BC and subtype B respectively, accounting for 63.8%,17.5% and 7.5%. Nine cases (11.3%) were classified as atypical HIV-1 recombinants. R263K mutation was detected in two CRF01_AE infected patients, and E138A mutation was detected in a patient infected with subtype B. The overall drug resistance rate for InIs was 3.8%. CRF01_AE infected individuals showed amino acid polymorphism at the site 50, 74, 119 and 153 relevant to InIs resistance with frequency of 5.9%, 2.0%, 13.7% and 4.0% respectively. The CRF07_BC infected individuals showed amino acid polymorphism at the site 50, 74 and 157 relevant to InIs resistance with frequency of 7.1% for each site. @*Conclusion@#The primary drug resistance rate of InIs among the newly diagnosed HIV infected people in Shenyang was low, but a small number of patients showed amino acid polymorphisms on InIs resistance sites. To interpret the significance of drug resistance mutations in InIs better, it is necessary to strengthen both the monitoring of HIV InIs resistance and the study on the drug resistance-relevant genotype and phenotype of HIV-1 strains epidemic in China.

The clinical outcomes and prognosis of older human immunodeficiency virus-infected patients under antiretroviral therapy / 中华传染病杂志

Objective To evaluate the clinical outcomes and prognosis of older human immunodeficiency virus (HIV )-infected patients under antiretroviral therapy (ART ) in China .Methods This study was carried out in a retrospective cohort of HIV-infected patients initiated ART between January 2004 and December 2012 at The First Affiliated Hospital ,China Medical University .The patients were enrolled and divided into two groups ,including <50 years group (young and middle-aged group) and≥50 years group (older group) .Immunological and virological responses and mortality were analyzed . Data were analyzed by t test ,chi-square test ,two-way analysis of variance and log-rank test .Results Totally 291 subjects were included ,among whom 97 subjects were older patients and 194 subjects were young and middle-aged patients .Male was predominate in both groups ,which accounted for 91 .8％ and 87 .6％ ,respectively .The CD4+ T lymphocyte count in the older group before treatment was (151 .9 ±96 .2) cells /μL ,which was significantly lower than that in the young and middle-aged group (183 .4 ± 93 . 5) cells/μL (t= 2 .657 , P=0 .009) .At month 12 of treatment ,the CD4+ T lymphocyte count in the older group was significantly lower than that in the young and middle-aged groups (t= 2 .120 , P=0 .035) ,while there was no statistically significant difference between the two groups at month 24 (t=1 .025 ,P=0 .299) .The percentage of CD4+ T lymphocyte count increasing to 500 cells/μL in the older and youth groups during follow-up were 11 .3％ and 16 .0％ ,respectively (χ2=1 .127 ,P =0 .376) .Log-rank analysis showed that the mean times of virus inhibition in older group and young and middle-aged group were 7 .9 (95％ CI:6 .8-8 .5) and 7 .6 (95％ CI:6 .5 -9 .3) ,respectively ,with no statistically significant difference (χ2 =0 .002 , P=0 .961) .Virological failure was reported in 4 patients (4 .1％ ) in older group and 11 patients (5 .7％ ) in young and middle-aged group . Chi-square test showed no statistically significant difference between the two groups (χ2 = 0 .15 , P= 0 .78) .During follow-up , 19 .6％ (19/97) in older group and 3 .6％ (7/194) in young and middle-aged group died .The former was significantly higher than the latter (χ2 = 21 .113 , P< 0 .01 ) .Conclusions Older patients show a poor immunologic response ,similar viral suppression and higher risk of mortality compared with young and middle-aged patients . Future research should be aimed at the feasible and specific strategy for early diagnosis and timely treatment for older patients to improve treatment efficacy and reduce mortality .

Study of natural history of Chinese patients with choroideremia / 中华实验眼科杂志

Objective To provide detailed clinical and molecular genetic findings and describe the characteristics of natural history in Chinese choroideremia (CHM) patients.Methods The patients with CHM who met the inclusion criteria of at least two visits over a minimum period of 5 years were recruited on a voluntary basis at the Ophthalmic Genetics Clinic in Peking Union Medical College Hospital from April 2009 to August 2017.Molecular genetic analysis results,best-corrected visual acuity (BCVA),color fundus photograph,optical coherence tomography (OCT),visual field (VF),full-field electroretinography (fERG) were obtained.This study protocol was approved by the Institutional Review Board of Peking Union Medical College Hospital (S-K125).Written informed consent was obtained from each participant.Results Ten Chinese Han patients from seven CHM families were included.The mutations were confirmed by molecular genetic analysis,and two novel mutations were found.The median age of 10 patients at first visit was 44 years (range 8-52 years).The mean first-last visit period was 6.08 years (range 5.03-7.24 years).The mean BCVA at first visit in logMAR equivalents was 0.56 (range 0.0-2.0) or approximately 0.28 decimal acuity.The correlation between BCVA at first visit and age showed that relative good vision remained until 35 years old and BCVA subsequently reduced rapidly.OCT showed a thickening of the central retinal thickness at early stage,followed by a thinning over decades.Outer retinal tabulation (ORT) was shown in some patients.There was a strong negative correlation (r=-0.861,P＜0.001) between residual VF and age.Five patients did not need to record fERG because of serious fundus lesions.Two patients exhibited decreased amplitudes for both rod and cone-driven responses,and three patients exhibited no fERG amplitudes.Conclusions The progression of CHM may be severer and faster in Chinese patients than that in Western patients.ORT is an important manifestation of OCT in CHM patients.VF and fERG are applicable to evaluate the condition of very-early phase of CHM.

Evaluation the performance of three HIV antigen-antibody combination assays in the detection of HIV in the window period / 中华检验医学杂志

Objective To evaluate the detectability of HIV antigen-antibody in the window period of acute infection by three HIV antigen-antibody assays.Methods Twenty-two samples of HIV seroconversion serum panels and thirty-seven HIV acute infected plasm samples from our laboratory collected from cohort study of men who have sex with men between 2009 and 2011,were assayed by ECLIA,CLIA and ELISA methods.All assays were evaluated for the ability to detect HIV in the window period,and the sensitivity of each assay for acute samples was analyzed.Chi square test was used for statistical analysis.Results The ability of detecting HIV in the window period of each assay was different.For HIV seroconversion serum panels,the results of ECLIA and CLIA assays were consistent,and the window period was shortened at least 1 to 5 days compared with ELISA assay.For HIV acute samples,all were HIV positive by ECLIA or CLIA assay,but for ELISA assay,94.6％ was positive.For samples before seroconversion,ECLIA and CLIA assay had the same sensitivity (93.5％),which is superior to ELISA assay (71.0％) (x2 =5.14,P ＜0.05).Conclusion The ability of detecting HIV in the window period was different for each assay.The results of ECLIA and CLIA assay are consistent,superior to ELISA assay.

A comparative study on the clinical performance of three fourth generation HIV diagnostic reagents / 中华检验医学杂志

Objective To compare the performance of fourth generation HIV antigen/antibody combined detection reagents for HIV early infection samples,international HIV seroconversion panel samples and routine clinical screening samples.Methods Thirty seven early HIV infected samples from the followup gays in Shen Yang between 2009 and 2011,66 seroconversion panel samples from BBI company (U.S.A),NABI company(U.S.A) and NIBSC company(U.K) and 703 routine HIV screening samples in the first hospital of China medical university in October 2010 were collected.All kinds of samples were tested by three diagnostic reagents based on chemiluminescence assay (CLIA),electrochemiluminescence assay (ECLIA) and enzyme-linked immunosorbent assay (ELISA) respectively.The detection sensitivity and specificity of these assays were analyzed.Results For 59 early infected and seroconversion samples,the sensitivities of both ECLIA and CLIA reagent were 96.61％ (95％ CI 91.5％-100.0％),higher than that of the ELISA kit (95％ CI 75.0％-92.9％) (x2 =5.341,P ＜ 0.05),which is 83.93％ ; Comparison among the three reagents for different subtypes of the antibody seroconversion samples showed that ECLIA had the highest sensitivity while CLIA was the lowest ; Detection sensitivity of the three reagents for the P24 antigen is CLIA ＞ ECLIA ＞ ELISA; With detection of 703 clinical routine screening samples,the specificities of three reagents were 100％ (CLIA),99.86％ (ECLIA) and 99.71％ (ELISA) respectively.Conclusions For the sensitivity of the fourth HIV diagnostic reagents CLIA and ECLIA are better than ELISA.The former two reagents are more suitable for identifying earlier HIV infection in clinic.

Screening of HIV-1 neutralizing antibody mimotopes in slow progressor from phage display peptide library / 中华检验医学杂志

ObjectiveTo screen mimetic HIV-1 neutralizing epitopes from plasma with high level neutralizing antibody,and to provide useful information for further study of the interaction between antigen and antibody.MethodsIn order to gain neutralizing antibody recognized mimotopes, we detected neutralizing antibodieslevelsof 11HIV-1infectedslowprogressorsbyPBMC-basedneutralization assays.High-titer HIV-neutralizing antibodies from plasma of SPs was used as the ligand for biopanning by phage-displayed random peptide library.Positive phage clones was evaluated by ELISA,sequenced,and analyzed for homology to HIV-1 env by local BLAST to deduce the neutralizing peptide.ResultsTwenty-two clones were obtained consistent with requirement through three rounds biopanning.After comparison analysis,twelve clones include C8 were obtained as mimotopes of neutralizing antibody,C40 located in gp41Ⅱ cluster with the highest titer by inhibition ratio may be as neutralizing epitope.Conclusion By the use of IgG antibodies from SPs to screen the phage random polypeptide library,one can acquire multiple phage mimetic peptides of HIV related antigen epitope.(Chin J Lab Med,2012,35:838-842 )

The comparison of the performance between third generation ELISA and fourth generation ELISA on acute and early HIV infection / 中华检验医学杂志

Objective To evaluate the performance of the third generation ELISA and the fourth generation ELISA for HIV-1 diagnosis assays on acute and early HIV-1 infected samples.Methods Sixtyseven acute/early HIV-1 infected samples were collected from the follow-up gays with seroconversion in Shen Yang city and from clinical patients in the First Affiliated Hospital of China Medical University with incomplete HIV-1 specific bands in western blot between 2008 and 2010.Third generation ELISA,fourth generation ELISA,western blot and HIV-1 viral load detecting were used for detecting these samples.The sensitivity,consistency were compared between third generation ELISA and fourth generation ELISA to detect the seroconversion samples and the window periods were abserved.Chi square test was used for statistical analysis.Results In the 67 acute/early HIV-1 infected samples,56 were HIV positive and 11 were HIV negative by the third generation ELISA.The sensitivity of the third generation ELISA was 83.6％ (95％ CI:72.5％ -91.5％); 63 were HIV positive,1 was at gray zone and 3 were HIV negative by the fourth generation ELISA.The sensitivity of the fourth generation ELISA was 94.0％ (95％ CI:85.4％ -98.3％),higher than the third generation ELISA(x2 =16.1,P ＜0.01).The consistency of the third generation ELISA and the fourth generation ELISA was 86.6％ ( 95％ CI:76.0％ - 93.7％).The earliest third generation ELISA positive sample was the sample collected 16 days after HIV infection and the earliest fourth generation ELISA positive sample was the sample collected 9 days after HIV infection.There was significantly different on the window periods between the third generation ELISA and the fourth generation ELLSA Conclusion The fourth generation ELISA had a higher sensitivity and shorter window period on acute/early HIV infected samples than the third generation ELISA,which is more suitable for the HIV early infection screening on high risk populations.

The influence of Mycobacterium tuberculosis co-infection and other factors on HIV-1 replication in Guangxi, China / 中华微生物学和免疫学杂志

ObjectiveTo investigate the influence of Mycobacterium tuberculosis (MTB) co-infection and other factors on the HIV replication level in antiretroviral treatment na(i)ve patients.MethodsSix hundred TB patients and 465 HIV infectors were recruited between April 2010 and September 2010.TB coinfections were diagnosed in HIV infected cases with chest X-ray,checking TB in sputum with anti-acid staining and culture of the sputum,histopatholo diagnosis and clinical diagnosis.HIV infections were screened in TB patients with the 3rd generation ELISA antibody test.Sixty-one antiretroviral treatment na(i)ve HIV/TB co-infectors and 34 HIV infectors with CD4 T cell count below 350 cells/μl were included in this study.Information about the demography,epidemiology and results of clinical diagnostic tests of HIV and TB was collected through pathography and questionnaires from all participants.HIV viral load were detected with COBAS AmpliPrep/COBAS TaqMan(R) System of Roche Company.ResultsThe viral load of HIV/TB co-infectors was (5.05±0.93) lg copies/ml,while the viral load of HIV infectors was (5.06±0.76) lg copies/ml,after control of age,race,marital status,education,route of HIV infection,HIV clade and CD4 T cell count,there was no significant difference between the two groups (P=0.94).CRF01_AE HIV-1 infection was associated with higher HIV viral load compared with non CRF01_AE (OR=8.07,95％ CI 1.07-61.20,P=0.04).ConclusionNo obvious effect of MTB co-infection on HIV replication level of HIV infected cases with relatively low CD4 T cell count in Guangxi region,while the CRF01_AE HIV infected individuals showed higher viral load,we should raise concern on the monitoring and treatment on this population.

Study on the relationship of the expression of the B7-H1 and disease progression in HIV/AIDS patients / 中华检验医学杂志

Objective To investigate the level of B7-H1 and its counter-receptor PD-1 expression in mDC and different subsets of T lymphocytes in HIV infected individuals in China and to analyze the correlation between the level of B7-H1/PD-1 and disease progression, and to demonstrate that PD-1/PD-L1-dependent inhibition is operating in HIV infected patients.Methods Percentage of B7-H1 and PD-1 expression in mDC, CD+4 T cells and CD+8 T cells from thirty-six untreated HIV infected patients and 20 health controls were selected and detected by flow-cytometry, its correlations with CD+4 T cell absolute counts and plasma viral loads were analyzed.Results The percentage of B7-H1 expression in mDC, CD+4 T cells and CD+8 T cells (mean 15.21, mean 20.63, mean 13.5)were higher than that of health controls (all P<0.05).The percentage of PD-1 expression in CD+4 T cells and CD+8 T cells (mean 17.91, mean 19.21)were higher than that of health controls (P<0.05, P<0.05). The level of B7-H1 and PD-1 expression were inversely correlated with CD+4 T-cell counts(mDC+B7-H1+:r=-0.647, P<0.01;CD+4B7-H1+:r=-0.489, P=0.002;CD+8B7-H1+:r=-0.372, P=0.026;CD+4PD-1+:r=-0.374, P=0.025;CD+8PD-1+:r=-0.455, P=0.005) and positively correlated with HIV viral load(mDC+B7-H1+:r=0.662, P<0.01;CD+4B7-H1+: r=0.426, P=0.01;CD+8B7-H1+:r=0.531, P=0.001;CD+4PD-1+:r=0.362, P=0.03;CD+8PD-1+:r=0.380, P=0.022).Conclusion The level of B7-H1 and PD-1 expression was associated with HIV disease progression, which provides a useful marker to define disease progression of HIV infection.

Study on gene polymorphism of HIV-1 B' nef and its influence on disease progression in northern China / 中华微生物学和免疫学杂志

Objective To explore the polymorphism of nef gene and conservation level of functionally important domains of nef as well as their influences on HIV-1 disease progression of HIV-1 B'infected individuals in northern China.Methods 30 long term nonprogressors(LTNPs)and 42 typical progressors (TPs)were selected.Provirus DNA was extracted from whole blood sample.The full nef gene was amplified by nested-PCR.PCR product was sequenced directly after purification.Phylogenetic analysis and amino acid sequence mutation was applied on nef sequences to explore the differences between LTNPs and TPs.Results At position 15,the S15R/K/N substitution was detected.The frequency of TPs(64.29%)wsa higher than LTNPs(33.33%,P<0.01,0R=3.60);R21K/E/H/I.Q,TPs and LTNPs mutation frequency was 59.52%and 93.33%(P<0.005,OR=0.11);At position 39,K39R/E/N was only detected in TPs(23.81%,P<0.005).Conclusion No significant deletion or defect associated with disease progression wsa detected in nef gene of HIV-1 B'.But it suggested that K/E/H/I/Q mutation at 21 st amino acid of nef associated the disease nonprogression.R/K/N at 15 th amino acid of nef and R/E/N mutation at 39th amino acid of nef associated the disease progression in.HIV-1 B'.All domaias of nef amino acids sequences were comparatively conservative.

B lymphocyte counts and Toil-like receptor 9 mRNA expression on cell from HIV-1 infected patients / 中华微生物学和免疫学杂志

Objective To study the B lymphocytes counts and the expression of TLR9 mRNA on B lymphocytes in peripheral blood from Chinese HIV-infected patients.Methods The cells from peripheral blood were stained with antibodies labeled with fluorescence and B lymphocytes were counted with flow cytometry.Using the method of magnetic activated cell sorting and real-time PCR,the expression of TLR9 mRNA was measured.Results The B lymphocytes counts in HIV/AIDS patients was significantly lower than that of healthy controls(P ＜0.01).The B lymphocytes counts in HIV/AIDS patients positively correlated with the CD4 +T cells counts(r =0.534,P = 0.006).The expression of TLR9 mRNA on B lymphocytes in HIV/AIDS patients was significantly lower than that of healthy controls(P =0.023),and positively correlated with the CD4 + T cells counts(r = 0.390,P = 0.040).Conclusion The B lymphocytes counts and the expression of TLR9 mRNA on B lymphocytes in Chinese HIV/AIDS patients were decreased due to HIV infection,which may correlate with disease progression.

Relationship between CTLA-4 expression in T cells and regulatory T cells and disease progression of HIV infected Chinese / 中华微生物学和免疫学杂志

Objective To detect the alternation of the level of CTLA-4 expression in T cells and regulatory T cells, and to study the relationship between CTLA-4 expression in T cells and regulatory T cells and disease progression of HIV infected Chinese. Methods Fifty-eight untreated HIV-1 infected patients were enrolled and the level of CTLA-4 expression in T cells and regulatory T cells were detected by flowcytometry. CD4+T cell numbers, viral load, level of CD95, HLA-DR, CD38 expression on T cells were measured to study the relationship between the level of CTLA-4 expression and disease progression of HIV infected patients. Results We found that the level of CTLA-4 expression in CD4+T cells continuously increased in long term nonprogressors (LTNP), asymptomatic HIV infected patients (HIV) and AIDS patients (P<0.05). The level of CTLA-4 expression in CD4+T cells was significantly correlated with CD4+T cell counts, the frequency of CD8+ CD38+T cells, CD4+CD95+T cells and CD8+CD95+T cells (P<0.05). There had no difference in the level of CTLA-4 expression in CD8+T cells among all groups and neither did we find the relationship between the level of CTLA-4 expression on CD8+ T cells and the CD4 counts, viral load, activation or apoptosis of T cells. The level of CTLA-4 expression in regulatory T cells of LTNP group was significantly lower than that of HIV and AIDS group (P<0.05). The level of CTLA-4 expression in regulatory T cells was significantly correlated with CD4 counts, the frequency of CD4+HLA-DR+T cells and CD8+HLA-DR+T cells (P<0.05). Conclusion The level of CTLA-4 expression in CD4+T cells and regulatory T cells is correlated with disease progression and the level of the activation of immune system of HIV infected Chinese and may play a role in the immune balance in HIV infection.

Study on the relationships between neutralizing antibody response against heterologous virus and disease progression of HIV type 1 B'/C infected individuals in China / 中华微生物学和免疫学杂志

Objective To study the relationships between neutralizing antibody response against heterologous virus and disease progression in Chinese HIV-1 B'/C infected individuals. Methods Plasmas from HIV-1-infected individuals, grouped as HIV chronically infected or AIDS according to CD4+ count and clinical symptom, were tested for neutralizing activity against the three HIV-1 isolates with very low homology in vitro. Six two-fold dilutions of each plasma sample (from 1/10 to 1/320) were tested against each virus from the panel. Giving a 50% reduction in p24Ag compared with normal human plasma control wells was defined as positive. The breadth of the cross-neutralizing response was defined based on the number of viruses that were effectively neutralized by any given patient-derived plasma sample. The magnitude of the crossneutralizing response was defined based on the average neutralizing titer against all heterologous viruses. Resuits We found that there revealed a significant difference between HIV chronically infected and AIDS group in the breaths and magnitudes of neutralizing heterologous virus. There was higher prevalence for the frequency of neutralizing heterologous virus in HIV chronically infected than AIDS. The results showed that there was positive correlation between the breadths and magnitudes of neutralizing response against heterologous virus and the plasma HIV RNA level in HIV chronically infected group, while not in AIDS group. There was no association between the breadth of the neutralizing responses against heterologous virus and CD4 T cell counts. Conclusion The capacity of neutralizing antibodies against heterologous virus varied among different disease stage. There were higher titers of neutralizing antibodies in HIV chronically infected than AIDS group. The loss of neutralizing antibodies in plasma from AIDS group appears to be associated with a narrowing of the antibody response during disease progression. These suggest that the presence of neutralizing antibodies against hetreologous virus was associated with disease progression.

Study on the relationship between the expression of TLR7/8 in monocytes and the disease progression of HIV-1 infection / 中华微生物学和免疫学杂志

Objective To examine the expression of TLR7/8 in monocytes purified from HIV-1 infected individuals and to study its association with disease progression. Methods Sixty-three HIV-1 infected individuals and 18 normal controls were enrolled. Monocytes were purified by MACS system and RNA of them was extracted by RNA mini kit of QIAGEN company. TLR7/8 expression was tested by real-time RT-PCR with ABI7500. Results It was found that the expression of TLR7 was strongly correlated with absolute CD4 count (r =0.614, P＜0.01) , so was TLR8 (r =0.419, P＜0.01). The expression of TLR7 in slow progressor (SP) group was higher than that in HIV-1 infected patients group, AIDS patients group and normal group (P ＜ 0. 05 ) . HIV group and normal group were strongly higher than AIDS group (P ＜ 0. 05). It was no significant differentiation of expression of TLR7 between HIV infection group and normal control group. The expression of TLR8 in SP group and normal group were significantly higher than that in AIDS group (P ＜ 0. 05). The expression of TLR8 was no singnificantly difference between SP group and HIV group or normal control group, so was it between HIV group or normal control group and AIDS group. Conclusion The expression of TLR7/8 in monocytes from HIV-1 infected patients significantly correlated with disease progression.

Amino acid mutatios of gp41 2F5 and 4E10 neutralizing epitopes of 92 HIV-1 infected individuals and AIDS patients in China / 中华微生物学和免疫学杂志

Objective To study the amino acid mutations in neutralizing antibody 2F5 and 4E10 conserved epitopes ELDKWA and NWFDIT of HIV-1 membrane proximal external region(MPER)in 92 HIV-infected individuals and AIDS patients in China,and to provide a basis for the neutralizing antobodies immunotherapy and a design of vaccines. Methods Nest-PCR methods were used to amplity genes of the HIV-1 env gp41 region.The amplified fragments were sequenced by double-deoxygen terminal method and translated into amino acids for analysis.The mutations of 2F5 and 4E10 neutralizing epitopes were identified by comparison with the epitopes reference data in HIV-1 Sequence Database.Results There were mutations on both 2F5 and 4E10 neutralizing epitopes.2F5 conserved neutralizing epitopes major mutations tocused on E662A(14.1%),K665S(17.4%),A667K(16.3%),and 4E10 conserved neutralizing epltopes major mutations included N671S(13.0%),D674S(3.3%),T676S(16.3%).The mutation rates of 2F5 and 4E10 epitopes were significanfly different between CRF_B'C-clade and B'-clade(P<0.05).The mutata rates of CRF_B'C-clade were higher than that of CRFOI_AE-clade in 2F5 epitopes(P<0.05).The mutation rates of B'-clade in 4E10 eiptopes showed significant difference in slow progressors,HIV-infected individuals and AIDS patients,respectively(P<0.05).Conclusion The HIV-1 patients in China are demonstrated diversified mutations in 2F5 and 4E10 neutralizing epitopes.The mutation degrees of amlno acids in conserved neutralizing epitopes are different in different subtypes.There may be a correlation between neutralizing epitopes mutations of 4E10 with disease progression.

Correlation between CD4+CD25+Foxp3+ regulatory T cells and disease progression in HIV infected long term non-progressors of China / 中华微生物学和免疫学杂志

Objective To study the association of CD4+CD8+Foxp3+ regulatory T cells with the HIV long term non-progressors(LTNP) in China. Methods Seventy-four HIV-1 infected patients (LTNP group, HIV group and AIDS group)and 16 normal controls were enrolled and the frequency of CD4+CD25+Foxp3+ regulatory T cells were detected by flow cytometry. To study the correlation between CD4+CD25+Foxp3+ regulatory T cells and disease progression, the absolute CD4+ T cells, viral load, apoptosis and activation of T cells were also examined. Results The frequency of CD4+CD25+Foxp3+ regulatory T cells in LTNP group was significantly lower than that in HIV and AIDS group (P<0.05). The frequency of CD4+CD25+Foxp3+ regulatory T cells was inversely related to CD4+ T cells and closely related to viral load and CD38, CD95 expression on CD4, CD8+ T cells (P<0.05). Conclusion The frequency of CD4+CD25+Foxp3+ regulatory T cells of HIV infected LTNP is significantly lower than typical progressors, which indicates that alternation of regulatory T cells may play a protective role in LTNP.

Studies of interaction between KIR alleles and the progression of HIV-1 infection in Chinese population / 中华微生物学和免疫学杂志

Objective To investigate the killer cell lg-like receptors (KIR) gene frequency of HIV-1 infected slow progressors(SP) and typical progressors(TP), and to analyze the interaction between KIR alleles and the progression of HIV-1 infection in Chinese population. Methods Eighty-one HIV-1 posi-tive individuals including 43 SPs and 38 TPs were recruited. Carriage of KIR genes was assessed using poly-merase chain reaction sequence-specific primers (PCR-SSP) assays. Results KIR2DS3 gene frequency was significantly lower in SP group (3.6%) than that in TP group (14.2%), P =0. 018 ,OR =0. 210,95% CI =0.053-0.833. The number of activating KIR genes was less in SP group than that in TP group, but was not significant (P = 0. 208). Conclusion Lower KIR2DS3 gene frequency may potentially be associated with slower progression to AIDS in Chinese population.

HLA-DQ Alleles in Patients with Pelvic Inflammatory Disease Caused by Chlamydia Trachomatis in Han Nationality of Northern China / 中华皮肤科杂志

Objective To investigate the possible association of HLA-DQ alleles with pelvic inflammatory disease (PID) caused by Chlamydia trachomatis in Han nationality in Northern China. Methods Thirty five Han Chinese patients with PID caused by Chlamydia trachomatis and 98 unrelated healthy individuals from the same area were genotyped for HLA-DQ gene alleles by the PCR-sequence specific oligonucleotide (SSO) method. Results Compared with the healthy controls, the frequencies of HLA-DQA1*0501 and HLA-DQB1*0301 allele were significantly increased and also associated with the antibody response to Chlamydia trachomatis heat-shock protein 60 (CHSP60). Conclusions These results may provide clues to reveal the susceptibility gene of chlamydial pelvic inflammatory disease in China and the immunogenetic mechanisms of the disease.