Clinical research progresss of antiviral drugs for the novel coronavirus pneumonia / 中华实验和临床病毒学杂志

The novel coronavirus (2019-nCoV or SARS-CoV-2) is a highly contagious and deadly virus that has infected more than 50 000 people and killed more than 1 000 people in 25 countries around the world. People who infected by the novel coronavirus may suffer from fever and cough, some may gradually appear breathing difficulties and other serious manifestations, some severe patients may have acute respiratory distress syndrome and septic shock leading to death. However, there are no definite and effective antiviral drugs for the novel coronavirus pneumonia all around the world. Therefore, this article aims to provide new idea for the effective treatment of the novel coronavirus pneumonia by summarizing the basic research and clinical progress of antiviral drugs at home and abroad.

Expression and identification of recombinant Clostridium difficile toxin B using Bacillus megaterium system / 中华传染病杂志

Objective To express and purify recombinant and biologically active Clostridium difficile toxin B (rTcdB). Methods The genes of TcdB were amplified by polymerase chain reaction (PCR) using chromosomal DNA from a toxigenic strain, and cloned into a shuttle vector pHis1522.The sequences of TcdB genes in the vector were verified by DNA sequencing. The construction was transformed into Bacillus megaterium protoplasts and the protein expression was driven by a xylose promoter. The purified protein was tested for biological activity. Results rTcdB was successfully purified from bacterial crude extracts. Approximately 5-10 mg of highly purified recombinant toxin was obtained from one liter of bacterial culture. The expressed rTcdB had molecular mass similar to the native toxin, and its biological activity was proved to be similar to its native counterpart after an extensive examination. Conclusion rTcdB with biological activities is successfully expressed in Bacillus megaterium.

Establishment and application of neutralization assay based on H5N1 avian influenza pseudotyped virus in vitro / 中华临床感染病杂志

Objective To establish neutralization assay based on H5N1 avian influenza pseudotyped virus in vitro and to evaluate neutralizing titer of convalescent serum from 2 patients with H5N1 avian influenza.Methods pHR-Luc,pCMV△8.2 and CMV/R-SH or CMV/R-TH were cotransfected into 293T cell by co-precipitation with calcium phosphate.Pseudotyped virus supernatant was harvested 72 h posttranofection and identified the expression of HA and P24 by Western blot,and then we analyzed infective activity of 200 μL supernatant of pseudotyped virus.293T cell integrated HA was prepared and anti-HA antibodies in convalescent serum were measured with FACS assay.Neutralizing titers of convalescent serums against Shenzhen and Thailand pseudotyped virus were determined based on calculating IC50 with neutralizing assay.Results Pseudotyped virus involved P24 and HA,and precursor protein HA0 could cleavage into HA1 and HA2 with biological activity.Pseudotyped virus possessed better infective activity,and RLA value was about 2 × 104 with 200 μL supernatant.Both convalescent serums contained anti-HA antibodies and had cross-reactivity against different virus clades with FACS assay.Both convalescent serums had neutralizingactivity and could cross-neutralize different virus clades.However,both serums'neutralizing titers against Shenzhen virus were higher than Thailand.Conclusion We successfully constructed infectious pseudotyped virus which integrated HA of Shenzhen or Thailand virus,and it could be used for evaluation of serum neutralizing activity fast,efficiently and safely with broadly application prospect.

Comparison of an in-house tuberculosis-specific IFN-γ release assays with T-SPOT TB in latent tuberculosis infection diagnosis among HIV-infected individuals / 中华检验医学杂志

Objective To evaluate the diagnostic value of two tuberculosis-specific IFN-γ release assays in latent tuberculosis infection among HIV-infected individuals. Methods The levels of tuberculosis antigen-specific IFN-γin 102 HIV patients from AIDS Outpatient Clinic of Shenzhen Third People's Hospital were detected by in-house tuberculosis-specific IFN-γ ELISpot assay and commercial T-SPOT TB kit, and tuberculin skin test (TST) were done at the same time. There were 66 males and 36 females,and the average age was 35. Results Seventeen HIV infected patients were positive in both IFN-γ ELISpot and T-SPOT TB methods, the sensitivity, specificity positive predictive value(PPV), negative predictive value(NPV) and compliance rates of ELISpot were 94. 4% ,94. 0% ,77. 3% ,98. 8% and 94. 1% ,respectively. Three patients were positive in both IFN-γELISpot and T-SPOT TB methods, the sensitivity, specificity, PPV, NPV and compliance rates of TST were 16. 7%, 98. 8%, 75.0%, 84. 7% and 84. 3%, respectively. The average number of spots using three kinds of antigen ESAT-6, Pool A,Pool B obtained were 26. 89 ±5. 77,18. 96 ±4. 75 and 14. 51 ± 3.77, respectively. Only ESAT-6 and Pool B have a statistically significant difference (H=7.557,P = 0.022 9), no significant difference was shown between other groups. There was no significant difference between the positive rate and the CD4+ T cellls number(x2 =0. 860 8 ,P =0. 650 2) ,as the same as the T-SPOT TB (x2 = 1. 396 4, P = 0. 497 5 ). Conclusions The performance of this in-house tuberculosis-specific IFN-γ ELISPot assay was comparable to T-SPOT assay in diagnosis of latent tuberculosis infection, and the sensitivity and specificity of both these two assays were all much higher than TST. They canbe recommended in diagnosing latent tuberculosis infection in HIV infected patients.

Study of the expression of complement regulatory protein CD59 on CD4+ T cells and its relationship with apoptosis in HIV infected patients / 中国基层医药

Objective To explore CD59 expression on CD4+T cells in HIV infected patients and its relationship with apoptosis.Methods 12 HIV infected patients and 10 healthy donors were performed in this study.The PBMC(peripheral blood monocyte)were collected and cell surface cytokine were stained,and then were evaluated with the BD FACSCanto flow cytometry.The expression of CD59 on T lymphocyte subsets were analyzed by FACSDiva software,and the apoptosis rate of CD59+CD4+T cells and CD59-CD4+T cells in every group was analyzed respectively,then the results were compared between groups.Results Compared with healthy donor,the expression of CD59 on T cells in HIV infected patients was significantly hisher(t=5.198,P＜0.01),and the apoptosis rate of CD59+CD4+T cells had significantly higher(t=5.968,P＜0.01).The apoptosis rate of CD59-CD4+T cells was no difference between two groups (t=0.1353,P=0.8577).Condnsion HIV infection increase CD59 expression on CD4+T cells,and CD59+CD4+T cells were prone to apoptosis.

The role of T helper type 17 cells in the pathogenesis of HIV/tuberculosis-coinfected patients / 中华传染病杂志

ObjectiveTo evaluate the IL-17 expression in HIV/tuberculosis-coinfected patients and its role in the pathogenesis of this coinfection.MethodsFifty-four HIV infected patients were divided into three groups:simple HIV infected group,HIV with latent tuberculosis infection (HIV+ LTBI) group and HIV coinfected with active tuberculosis (HIV+ ATB) group.The whole blood intracellular cytokine staining was performed and samples were then detected by BD FACSCanto.The expressions of CD4+ IL-17+ T cells and CD4+ IFNγ+ T cells were analyzed using FACSDiva software.Comparison between groups was done by independent sample t test.ResultsThe CD4+ T cell count and viral load among these three groups were comparable.There were no significant difference of the expression of CD4+ IL-17+ T cells between simple HIV infected group and HIV+ LTBI group (1.40 ± 1.01) ％ vs (1.29±0.86) ％,(t=0.336,P＞0.05),but both of these two groups were much higher than HIV+ATB group (t=3.680,t=2.516,P＜0.05).There were no significant differences of the expression of CD4+ IFNγ+ T cells among these three groups [(32.8±24.0)％ vs (40.3±1 21.9) ％ vs (46.1±31.2)％,(t=-0.939,t=-1.602,t=-0.646,P＞0.05)].ConclusionThe Th17 response is down-regulated in HIV/tuberculosis-coinfected patients,which may play an important antitubercular role in the pathogenesis of coinfection.

Comparison of efficacy and safety of pegylated interferon alfa-2a or adefovir dipivoxil monotherapy with combination therapy in HBeAg positive chronic hepatitis B patients / 中华传染病杂志

Objective To compare the clinical efficacy and safety of pegylated interferon α-2a (Peg IFN α-2a) or adefovir dipivoxil(ADV) monotherapy and their combination therapy in HBeAg positive chronic hepatitis B (CHB) patients. Methods An open randomized controlled multicenter clinical trial was performed. One hundred and twenty cases with CHB were divided into 3 groups: Peg IFN α-2a monotherapy (group A), ADV monotherapy (group B) and Peg IFN α-2a plus ADV combination therapy (group C). The virological response (VR), serological response (HBeAg, HBsAg clearance and seroconversion), biochemical response (BR) and sustained response (SR) were tested at week 24 and 48 of therapy and week 48 of follow-up after end of treatment (EOT) for'evaluation of therapeutic effects, safety and drug resistance. The efficacy was compared using X2 test. Results At week 48 of treatment, the VR (HBV DNA ≤500 copy/mL) rates were 36. 8%(14/38), 37. 5%(15/40) and 62. 9% (22/35), respectively in groups A, B and C; that in group C was higher than those in groups A and B (X2 = 4. 933, 4. 801, respectively; both P < 0. 05); HBeAg seroconversion rates in three groups were 44. 7% (17/38), 17. 5% (7/40) and 51. 4% (18/35), respectively. At week 48 of follow-up,SR rates in three groups were 34. 2%(13/38), 15. 0%(6/40) and 48. 6% (17/35), respectively; those in groups C and A were higher than that in group B (X2 = 9. 894,P<0. 01;X2 =3. 903, P<0. 05, respectively). Conclusions VRs at week 24 and 48 of Peg IFN α-2a plus ADV combination therapy are better than Peg IFN α-2a or ADV monotherapy. SRs at week 48 of follow-up after Peg IFN α-2a monotherapy and combination therapy are both better than ADV monotherapy.

The effect of Th17 cells on A(H1N1) influenza virus clearance / 中华传染病杂志

Objective To investigate the phenotype, frequency of Th17 cells and the association between Th17 cells and viral clearance in patients with H1N1 influenza A. Methods Three groups including 70 confirmed patients with H1N1 influenza A, 30 patients with seasonal influenza as well as 68 healthy subjects as controls were enrolled in this study. The percentages of Th1, Th2, Treg and Th17 lymphocytes in the peripheral blood were determined by intracellular staining and flow cytometry. The levels of interferon-γ (IFN-γ), transforming growth factor-beta (TGF-β),interleukin-6 (IL-6) in plasma and supernatant of the peripheral blood mononuclear cell (PBMC)culture were quantified by enzyme-linked immunosorbent assay (ELISA). Viral load in nasopharyngeal swabs was detected by real time quantitative reverse transcription-polymerase chain reaction (RTPCR). Data were analyzed by one way ANOVA and liner correlation analysis. Results The percentage of Th17 cells in H1N1 influenza A patients was (2. 740±0. 210)%, which the percentage of was significantly decreased compared to healthy subjects (3. 443 ±0. 154)% and seasonal influenza patients (3. 443±0. 277) % (F=4. 242, P＜0. 05); while the percentage of Thl, Th2 and Treg cells were not significantly different among these groups. Moreover, the TGF-β level in plasma of H1N1 influenza A patients was (10±8) ng/mL, which was significantly lower than healthy subjects (43 ±32 ) ng/mL and seasonal influenza patient ( 18 ± 10) ng/mL ( F= 17.72, P＜0.01 ). The TGF-β level in the supernatant of PBMC culture of H1N1 influenza A patients was (782 ± 736) pg/mL, which was significantly lower than healthy subjects (1462±315) pg/mL and seasonal influenza patients (1481 ±348) pg/mL (F=5. 730, P＜0.01). Additionally, the viral clearance period was inversely correlated with the percentage of Th17 cells (r=-0.38, P=0.02). Conclusions The proportion of Th17 cells in patients with H1N1 influenza A is significantly decreased, which is closely correlated with the level of TGF-β. This decrease may results in the delayed viral clearance.

Analysis on clinical features, viral load and viral shedding period of patients with mild or severe H1N1 influenza A virus infection / 中华传染病杂志

Objective To analyze clinical and laboratory features, viral load and viral shedding period of patients with mild or severe H1N1 influenza A infection. Methods Seventy mild cases and 16 severe cases with concurrent pneumonia were included from Shcnzhen area for analysis.Nasopharyngeal-swab specimens of patients were collected and viral load was detected by real-time quantitative polymerase chain reaction (PCR) assay during their hospitalization. The viral load and viral shedding period were compared between patients over 14 years old and less than 14 years old, and between 70 mild cases without pneumonia and 16 severe cases with pneumonia. The statistic analysis was performed using t test and chi square test. Results The most common symptoms and signs of the patients were fever, cough and enlargement of tonsils. However, the severe cases suffered more frequently from cough, dyspnea and high fever compared with the mild cases (x2 = 10. 9 and 14.3, respectively, t=3.65; both P＜0.01 ). The levels of white blood cell (WBC) count and alanine arninotransferase (ALT) of severe patients were both significantly higher than those of mild patients(t= 3.2, 2.4,respectively; both P＜0.05). The chest radiology of the severe cases showed interstitial pneumonia,mostly with ground glass image. The viral load of patients under 14 years was significantly higher than those over 14 years [(4.86± 1.23) lg vs (4. 17±0.89) lg; t=2.3, P＜0.05], and the viral shedding period of patients under 14 years was significantly longer than those over 14 years [(5.33±0. 49) d vs(3. 63±0.28) d; t=3.4, P＜0.01]. The severe patients also displayed significantly higher viral load and prolonged viral shedding period than the mild patients [(6. 36±1. 44) lg vs (4. 35±0.99) lg, t=6.1,P＜0.01; (5.75±1.77) d vs (4. 24±1. 96) d, t=3.2, P＜0.01]. Conclusion Age anddisease severity of patients with H1N1 influenza A infection are significantly associated with viral load and viral shedding period.

The role of CD4+CD25+Foxp3 regulatory T cells in patients with chronic hepatitis B / 中华传染病杂志

Objective To investigate the role of CD4+CD25+Foxp3 regulatory T cells in chronicity of hepatitis B and viral clearance of hepatitis B virus(HBV).Methods Nineteen patients with chronic active hepatitis B(CAH).21 HBV carriers(AsC)and 12 patients with resolved HBV infection and 1 5 healthy controls were enrolled.The frequency and phenotype of peripheral CD4+CD25+Foxp3+ T cells were detected by flow cytometry.CD4+CD25+T cells were sorted by magnetic-activated cell sorting(MACS)assay.Level of Foxp3 mRNA in CD4+CD25+T cells was examined by real time polymerase chain reaction(PCR)assay.The data were analyzed by one-way ANoVA or nonparametric statistics.Results Both frequencies of CD4+CD25+Foxp3+T cells and levels of Foxp3 mRNA in CD4+CD25+T ceils in patients with CAH or AsC were significantly higher than those in healthy controls Or resolved HBV infection(F=6.8,F=3.72,respectively;both P<0.05).Accumulation of Foxp3+T cells in liver tissue of CAH patients was higher than that of healthy controls,while that in AsC was lower than CAH.The frequency of CD4+CD25+Foxp3+T cells of hepatitis B e antigen(HBeAg)positive patients(including CAH and AsC)was significantly higher than that of HBeAg negative patients(t=2.3,P<0.05),and that of antFHBe negative patients were significantly higher than anti-HBe positive patients(t=2.4,P<0.05).Furthermore,the frequency of CD4+CD25+Foxp3 regulatory T cells was positively correlated with serum HBV DNA level of patients with chronic hepatitis B(r=0.56,P<0.01).Conclusion The findings have important implication in the understanding of the role of CD4'CD25'regulatory T cells in chronicity and viral clearance in HBV infection.

Construction of pseudotype retrovirus which integrates hemagglutinin of H5N1 avian influenza virus isolated from human in Shenzhen / 中华微生物学和免疫学杂志

Objective To construct pseudotype retrovirus which integrates hemagglutinin(HA)of H5N1 avian influenza virus(AIV)isolated from human in Shenzhen.Methods AIV HA gene was amplified bv RT-PCR,then it was ligated with pGEM-T vector,and identified by restriction enzyme digestion and sequenced.HA gene was cloned into CMV/R vector at the site of Sal Ⅰ and BamH Ⅰ.pHR-Luc,pCMV&8.2 and CMV-HA were co-transfected into 293T cell by co-precipitation with calcium phosphate.The pseudotype virus supernatant was harvested 72 h post-transfection and ultracentrifugation,and the HA and P24 expression on the surface of pseudotype virus was analyzed by western blot.Meanwhile.the infection activity of HIV-HA pseudotype virus was identified in different kinds of cell lines,including MDCK,HeLa,CHO and 293T.Results A/Shenzhen/406H/06 belonged to subclade2.3 with open reading frame(ORF)of HA gene encoded 567 amino acides,whose accession number was EF137706 in GenBank.HA gene was cloned into CMV/R successfully.After co-transfection of above vectors,it revealed that HA protein could integrate pseudotype virus by western blot,and precursor protein HA0 could cleavage into HA1 and HA2 with biological activity.Finally.HIV-HA pseudotype virus could infect 4 kinds of cell lines,which indicated its property of infectivity and catholicity.Conclusion The pseudotype retrnvirns wassuccessfully constructed,which can integrate HA protein of A/Shenzhen/406H/06 and had property of infectivity.It call be used in the further research,including selection of neutralizing antibodies and epitope analysis.

Development of a serological ELISA kit for detection of EV71 infection associated with hand-foot and mouth disease and its clinical application / 中华检验医学杂志

Objective To develop an ELISA(Enzyme-Linked Immunosorbent Assay)diagnostic kit for early rapid detection of sarum anti-EV71 antibody and evaluate its clinical application value.Methods Recombinant protein VP1 of EV71 were prepared and purified as an immobilized antigen for establishment of an indirect ELISA for detection of serum anti-EV71 IgM and anti-EV71 IgG.Compared with RT-PCR.isolation of EV71 and micro-neutralizing assay.the clinical application value of anti-EV71 IgM and anti-EV71 ISG in the diagnosis of EV71 disease was evaluated.Results In comparison with RT-PCR.the sensitivity,specificity,positive predictive value and negative predictive value of anti-EV71 IgM antibody were 83%,85%,81%and 87%,respectively.The sensitivity,specificity,positive predictive value and negative predictive value of anti-EV71 IgG antibody were 72%,74%,68%and 77%.respectively.Compared with viral isolation assay.the sensitivity and specificity of anti-EV71 IgM antibody were 85%and 97%,respectively.The sensitivity and specificity of anti-EV71 IsG antibody were 75%and 77%,respectively.In addition.the titers of anti-EV71 IgG antibody were significantly correlated with the titers of neutralizing antibody to EV71 by linear regression analysis(r=0.72,P＜0.05).Finally,the serum titers of anti-IgG from patients with EV71 associated hand food and mouth disease at convalescent stage exhibited significantly higher than that of the same patients at acute stage(P＜0.01),but the titers of anti-IgM had no significant difference(P＞0.05).Conclusions With VP1 recombinant protein used as an immobilized antigen,an indirect ELISA diagnostic kit was successfully develooed for detection of serum anti-human EV71 IgM and anti-human EV71 IgG antibodies.

Role of CD4~+ CD25~+ regulatory T lymphocytes in the pathogenesis of murine pulmonary tuberculosis / 中华传染病杂志

Objective To investigate the role of CD4 ~+ CD25~+ regulatory T lymphocytes (Treg)in modulating the cellular immune response and pathogenesis of murine pulmonary tuberculosis.Methods Inactivation of Treg was achieved by intraperitoneal injection anti-CD25 (clone PC61,50 μ/mouse) in PC61 group, and rat-IgG (50 μ/mouse) was injected intraperitoneally in control group. All the mice were inoculated intravenously with H37Rv 0. 1 mL (1 × 10~6 CFU) 3 days after Treg inactivation. The effects of Treg inactivation in different tissues were analyzed by flow cytometry. The cellular immune response, pulmonary histopathology and bacterial load were determined in vitro at different time points. The data were compared using homogeneity of variance F test and non-paired t test. Results In spleen, the percentages of Treg/CD4 T lymphocytes in PC61 group and control group were (21. 13± 3. 58)% and (30. 42± 4. 20)%, respectively at day 10 of inoculation (t = 2. 38, P < 0. 05), and those were (16. 12 ± 1. 26)% and ( 17. 34± 1. 62)%,respectively at day 30 of inoculation (t = 0. 84,P>0. 05). The percentages of Foxp3~+/CD4~+ T lymphocytes in PC61 group and control group were (32. 07 ± 3. 95)% and (60. 55 ± 5. 48)%,respectively at day 10 of inoculation (t = 5. 96, P<0. 05). Similar results were achieved in the peripheral blood. Bacillus calmette-guerin (BCG)-specific 1L-17 (ng/L) secreted by murine spleen cells in PC61 group and control group at day 10, 30 and 60 of inoculation were 5. 1± 0.9 vs 0, 43. 1± 10.0 vs5. 9± 2. 8 and 124.8 ± 5.8 vs 102. 5±8. 1, respectively (t = 7. 90, t=5. 10,t = 3. 19; all P<0.05); those of BCG-specific IFN-γ (ng/L) were 28. 4 ± 8. 2 vs 4. 0±1. 3, 685. 9± 128. 6 vs418. 7±20.4 and 310.9±119. 7 vs 32. 8±7. 5, respectively(tO = 4. 21,t = 8. 43, t = 3. 27; all P<0.05);those of TNF-a (ng/L) were 38. 6±5.0 vs 16. 3±4. 0, 112. 9 ±12. 3 vs 71. 5±12. 6 and 86. 2±8. 2vs0, respectively(t = 4. 95, t=3. 33,t/=14.8; all P<0. 05). The lung bacterial load at day 10 of inoculation in PC61 group was lower than that in control group (t = 4. 63, P < 0. 01), but the differences were not significant thereafter. The changes of lung histopathology at late stage of infection (day 120) in PC61 group were less severe than those in control group. Conclusions Murine Tregs increase dramatically after Mycobacterium tuberculosis infection. Treg could inhibit the specific cellular immunity against Mycobacterium tuberculosis, and therefore, may facilitate the persistent infection of Mycobacterium tuberculosis and development of tuberculosis.

Use of IFN-γ release assay in latent tuberculosis infection diagnosis in general and HTV-infected populations / 中华微生物学和免疫学杂志

Objective To assess the validity of a newly developed in-house ELISPOT IFN-γ release assay (IGRA) for the detection of latent tuberculosis infection among HIV infected individuals. Methods In-house ELISPOT assay were performed, together with a tuberculin skin test in 205 health controls and 110 HIV infected individuals , who had no signs of active tuberculosis at time of enrolment . Results Using the ELISPOT assay, positivity rates for the 205 health controls, 110 HIV infected individuals and 47 AIDS patients on highly active antiretrovial therapy (HAART) were 7. 3% , 24.5% , 29. 8% , respectively. These results indicated that the positive rates obtained from HIV infected individuals (include patient on HAART) was significantly higher than health controls( P ＜ 0.001). We found no significant correlation between the CD4 cell count and positivity of ELISPOT assay (P ＞0.05 ). The proportion of subjects with a positive response to ELISPOT assay were higher than the proportion of tuberculin skin test(TST) responders(P＜0.0001) in HIV infected individuals. Conclusion Our study indicates that IGRA using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals.

Significant increasing of homing molecules expression on T lymphocytes in AIDS patients after treatment with HAART / 中华微生物学和免疫学杂志

Objective To evaluate the homing molecules expression of CD49d, CCRg, CD62L on T lymphocytes in AIDS patients before and after treatment with HAART. Methods The study was per-formed in 42 cases of AIDS patients and 18 cases of healthy controls. The expression of CD49d, CCR9 and CD62L on T lymphocytes in AIDS patients and healthy controls were analyzed by flow cytometry. Software BD FACSDiva was used to calculate the percentage of expression. Results The number of peripheral CD4~+ T lymphocytes in group on-HAART was significantly increased compared with group pre-HAART (P<0.01) ; the frequency of CD3~+ CD49d~+, CD3~+CCR9~+, CD3~+CD62L~+, CD3~+CD4~+, CD4~+CD49d~+,CD4~+CCR9~+, CD4~+CD62L~+, CD8~+CD49d~+, CD8~+CD62L~+T lymphocyte in group pre-HAART were statistically decreased compared with group on-HAART and controls(P<0.05) ; The frequency of CD3~+ CD8~+ T lymphocytes was significantly increased compared with group on-HAART(P<0.05) ; the frequency of CD3~+ CCR9~+, CD8~+CCR9~+, CD8~+CD62L~+ T lymphocytes in group on-HAART were significantly de-creased than controls (P<0.001). Conclusion Not only the number of T lymphocytes sub-group, but the expression rate of gut homing molecules CD49d and CCR9, lymph node homing molecule CD62L on T lym-phocytes was changed in AIDS patients : the lower expression frequency of gut homing molecules CD49d and CCR9, lymph node homing molecule CD62L. Anti-virus therapy could partially reverse the immunologic pathological phenomena. CD49d, CCR9 and CD62L may be suggested to indicate the progression of AIDS and immunologic reeonstitution after HAART.

DC-SIGNR polymorphisms and its association with HIV-1 infection / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the association of the polymorphism of homologue of dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN related, DC-SIGNR) gene with the susceptibility to HIV-1 infection.</p><p><b>METHODS</b>The distribution of the DC-SIGNR variants in the tandem repeat region and their association with HIV-1 infection in a cohort composed of 345 HIV-1 seropositive and 468 high-risk HIV-1 seronegative individuals was examined.</p><p><b>RESULTS</b>There are 14 genotypes and 5 alleles in the DC-SIGNR repeat regions in the cohort. Although the most common DC-SIGNR allele among Chinese Han population and the Caucasian population is 7, it was found in a higher frequency in the Chinese than in Caucasians (67.1% vs.46.0%, P<0.01). HIV-1 seropositive individuals had a lower frequency of the genotype 7/7 than the high-risk seronegative individuals (38.55% vs. 48.29%, P=0.0057), but a higher frequency of genotype 9/5 (4.35% vs. 1.07%, P=0.0029).</p><p><b>CONCLUSION</b>These results suggest that the tandem-repeat polymorphisms of the DC-SIGNR gene in the Chinese Han population exhibit unique genetic characteristics previously unrecognized in the Caucasian population. Genotype 9/5 seems to be a risk factor for HIV-1 infection in the Chinese population.</p>

Clinical study on YMDD mutation and pre-core C region and core promotor region mutation of the patients with chronic hepatitis B virus receiving lamivudine therapy / 中国基层医药

Objective To mvesugate the Tate of YMDD mutation accompamed with pre-core(region and core promotor region mutation and the clinical significance.Methods YMDD mutation and pre-core(at 1896 nu- cleotide)region and core promotor region(at 1762.1764 nucleotide)mutation were detected from the 122 patients with chronic hepatitis B virus after receiving lamivudine treatment above 6 months.Results 40 cases were tested for YMDI)mutations in 122 HBV patients with lamivudine treatment,and the positive rate of YMDD mutation was 32.8 %.After YMDD mutation,ALT,AST and HBV DNA of the patients significantly increased(P0.05).Conclusion The patients with YMDD mutation had higher rate of pre-core region(at 1896 nucleotide)and basal core promotor region(at 1762, 1764 nucleotide)mutation than those without YMDD mutation,but there was no correlation between the mutation and the deterioration of disease condition and the bad prognosis.

Chest X-ray imaging of patients with SARS / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the chest X-ray manifestations of SARS cases.</p><p><b>METHODS</b>A retrospective study was conducted among 52 clinically confirmed SARS patients from February 9 to May 10, 2003. Chest X-ray scanning was performed at a interval of 1 - 3 days according to the requirements. The manifestations and special features of SARS in X-ray were analyzed.</p><p><b>RESULTS</b>Small or large patchy shadows with intensive density in both lungs were observed in 31 cases, ground-glass like opacification in 16, small patchy shadows in one lung lobe or one lung segment in 18, nodular shadows in one lung segment in 1, and increased lung marking in lung interstitial tissues in 2. Rapidly changing consolidations revealed in chest X-ray images were found to be associated with SARS infections, and they were not affected by treatment with antibiotics.</p><p><b>CONCLUSION</b>Chest X-ray provides a sensitive and specific method for the diagnosis and treatment of SARS, and those present with symptoms and signs should undergo chest X-ray scanning every 1 - 3 days.</p>

The genetic polymorphisms of DC-SIGN and DC-SIGNR among female sex workers / 中华皮肤科杂志

Objective To determine the genetic polymorphisms of DC-SIGN and DC-SIGNR among HIV negative Chinese female sex workers. Methods The 69 bp tandem repeat numbers in exon 4 of the DC-SIGN and DC-SIGNR were examined by PCR in 234 HIV-1-seronegative female commercial sex workers. Results It was found that 4 of 234 individuals were heterozygous in DC-SIGN. For DC-SIGNR, the allele frequencies were seven times repeated in 65.2%, 5 in 18.4%, and 9 in 11.9%. Those patterns of alleles frequencies were significantly different compared with those reported in the Caucasians residing in Europe. Conclusion Polymorphisms of DC-SIGN repeat region seem to be infrequent in Chinese female sex workers and those of DC-SIGNR are different from what reported in other races.

Genetic analysis of human immunodeficiency virus type 1 strains from AIDS patients in Shenzhen / 中华检验医学杂志

Objective To identify subtypes of human immunodeficiency virus 1(HIV-1)strains from the AIDS patients in Shenzhen and determine whether the HIV-1 subtypes differ in disease progression.Methods HIV-1 env gene was amplified by the nest-RT-PCR from plasma obtained from 26 patients with AIDS in Shenzhen. The C2-V3 regions were sequenced to identify subtypes The plasma viral loads and CD4T lymphocyte were measured as the same time.Results Phylogenetic trees showed that the 12 AIDS patients had subtype B in which, one was close with the U.S reference strain and 11 with the Chinese Yunnan reference strain;13 AIDS patients had subtype CRF01-AE from Thailand;There were no differences in the CD4 cell count and plasma HIV-RNA levels between individuals infected with subtypes B and CRF01-AE.Conclusion Our study indicated that HIV-1 subtype B and CRF01-AE strains were present in AIDS patients in Shenzhen. There was no evidence that the subtypes of virus could determine disease progression.