Risk factors associated with low-level viremia in human immunodeficiency virus/acquired immunodeficiency syndrome patients after anti-retroviral therapy / 中华传染病杂志

Objective:To investigate the risk factors of low-level viremia (LLV) among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients after combined anti-retroviral therapy (ART), and to provide evidence for reducing the risk of LLV.Methods:It was a cross-sectional observation study that enrolled HIV/AIDS patients with LLV (plasma HIV-1 RNA was 50 to 1 000 copies/mL) receiving ART over one year (LLV group) from January 2019 to December 2020 in Guangzhou Eighth People′s Hospital, Guangzhou Medical University. Contemporaneous patients with ART over one year and successful viral suppression (plasma HIV-1 RNA<50 copies/mL) were randomly selected as the control group (suppression group) with a ratio of 1∶2.5, and the risk factors for LLV were analyzed by unconditional logistic regression.Results:A total of 128 and 297 patients were enrolled in LLV group and the suppression group, respectively.ART durations were 3.62(1.83, 4.89) years and 4.91(2.90, 5.88) years, respectively. Multivariate logistic regression analysis showed that the risk factors associated with LLV included the age of initial ART treatment above 50 years old (odds ratio ( OR)=1.82, 95% confidence interval ( CI) 1.01 to 3.26, P=0.046), the baseline HIV-1 RNA over 1×10 5 copies/mL ( OR=2.18, 95% CI 1.30 to 3.68, P=0.003), using the simplified initial ART regimen ( OR=1.82, 95% CI 1.02 to 3.26, P=0.044), missing medication more than three times per year ( OR=2.49, 95% CI 1.55 to 4.01, P<0.001) and changing regimen during ART ( OR=1.90, 95% CI 1.14 to 3.14, P=0.013), while the duration of ART longer than five years could reduce the risk of LLV ( OR=0.37, 95% CI 0.22 to 0.64, P<0.001). In patients with simplified initial ART regimen, the baseline CD4 + T lymphocyte count of whom with LLV was lower than that of whom with viral suppression, and the difference was statistically significant (94.00 (24.00, 281.00)/μL vs 375.00 (310.00, 435.00)/μL, Z=-2.60, P<0.001). Conclusions:The occurrence of LLV is related to the age of initial ART treatment, the baseline HIV-1 RNA, the initial ART regimen, the medication adherence and the change of ART regimen during ART. Strategies may be beneficial to reducing the risk of LLV for HIV/AIDS patients, such as initiating ART as soon as possible, using simplified regimen as initial regimen with caution in patients with low baseline CD4 + T lymphocyte counts, strengthening compliance education, avoiding unnecessary ART regimen changes.

Clinical features of acquired immunodeficiency syndrome patients complicated with peripulmonary occupational lesions / 中华传染病杂志

Objective:To analyze the clinical features of acquired immunodeficiency syndrome (AIDS) patients complicated with peripulmonary occupational lesions.Methods:Fifty-five AIDS patients with peripulmonary occupational lesions treated in Guangzhou Eighth People′s Hospital from January 2012 to January 2019 were included, and the clinical data of patients were retrospectively analyzed. According to the results of lung biopsy, the patients were divided into Mycobacterium infection group, fungal infection group and tumor group. The clinical characteristics, the proportion of different CD4 + T lymphocyte counts and chest computed tomography (CT) features of the three groups were compared. Chi square test was used for comparison among the three groups, and Bonferroni method was used to correct the test level for pairwise comparison. The significance level was 0.016 7 because of three pairwise comparisons. Results:Among 55 AIDS patients complicated with peripulmonary occupational lesions, pulmonary biopsy showed 14 cases with Mycobacterium infection, 12 cases with fungal infection and 15 cases with tumor lesions. Mixed diseases were found in 11 patients, including seven cases with Mycobacterium and fungus coinfection, four with tumor complicated with fungus and (or) Mycobacterium. Three with chronic interstitial pneumonia. The main clinical manifestations of 55 patients were fever, expectoration, fatigue, weight loss and superficial lymph node enlargement. There were no significant differences in symptoms/signs, white blood cell counts, hemoglobin levels, alanine transaminase and creatinine among Mycobacterium infection group, fungal infection group and tumor group (all P>0.05). There was significant difference in anti-retroviral therapy (ART) acceptance among the three groups ( χ2=15.165, P<0.01). However, the results of pairwise comparison between groups showed that there was significant difference between fungal infection group and tumor group ( χ2=7.514, P<0.016 7), while there was no significant difference between Mycobacterium infection group and tumor group, Mycobacterium infection group and fungal infection group ( χ2=0.255 and 5.306, respectively, both P>0.016 7). There were significant differences in clinical outcomes among the three groups ( χ2=15.119, P<0.01), and the pairwise comparison between the Mycobacterium infection group and the tumor group, and the fungal infection group and the tumor group showed significant differences ( χ2 =10.311 and 9.095, respectively, both P<0.016 7). The cases with CD4 + T lymphocyte count ≤50/μL, 51-<200/μL and ≥200/μL in Mycobacterium infection group were three cases, one case and 10 cases, respectively; those in fungal infection group were 10 cases, two cases and 0 case, respectively, and those in tumor group were one case, two cases and 12 cases, respectively. The difference was statistically significant ( χ2=21.284, P<0.01). Chest CT showed that there was significant difference in the types of space occupying lesions among the three groups ( χ2=13.308, P=0.003), and pairwise comparison between the two groups showed that there was significant difference between the Mycobacterium infection group and the tumor group ( χ2=11.312, P<0.016 7), while there were no significant differences between the Mycobacterium infection group and fungal infection group ( χ2=0.931, P>0.016 7), and the fungal infection group and the tumor group ( χ2=7.053, P>0.016 7). There was significant difference among the three groups in calcification focus ( χ2=8.524, P=0.004), while there was no difference between the Mycobacterium infection group and fungal infection+ tumor group ( χ2=10.982, P<0.016 7). Conclusions:Mycobacterium infection, fungal infection and tumor are the main types of peripulmonary occupational lesions in AIDS patients. The differential diagnosis could be made by combining with chest CT features, ART acceptance and CD4 + T lymphocyte level.

Therapeutic Effect of Spleen Low Molecular Weight Extracts on Leukopenia Caused by Epirubicin in Mice and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism.@*METHODS@#The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed.@*RESULTS@#In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05).@*CONCLUSION@#The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.

Single cell RNA sequencing of bone marrow mononuclear cells from elderly patients with hip fracture / 中华创伤骨科杂志

Objective:To determine whether subpopulations may exist which are related to regulation of immunization or inflammation in bone marrow mononuclear cells (BMMNCs) from 2 elderly patients with hip fracture and whether there might be any difference in the subpopulations between them.Methods:Two elderly patients with hip fracture were enrolled in this study. Their venous blood was harvested to determine subpopulations of complement (C)3, C4, interleukins (IL)-2, IL-6, IL-10, and lymphocytes. Single cell RNA sequencing (scRNA-Seq) was used to group their BMMNCs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed of the top 20 differentially expressed genes for each subpopulation to judge the main function of each subpopulation. The subpopulations and the key genes related to regulation of immunization or inflammation were found out. The relationships were explored between subpopulations and prognosis of the patients.Results:By the venous blood indexes, IL-10 was slightly high in patient A; C3 below normal, C4 close to the lower normal limit, IL-2, IL-6 and IL-10 were significantly high, CD8 +T % was low, and CD4 +/CD8 + high in patient B. After scRNA-Seq and bioinformatics analyses, the BMMNCs in the 2 patients were divided into 5 subpopulations. GO and KEGG enrichment analyses showed that the functions of subpopulation 2 and subpopulation 4 were related to immunization or inflammation. CCL4, CCL5, LTB and CXCR4 in subpopulation 2 and C1QA, C1QB, CD14 and SPP1 in subpopulation 4 were related to the regulation of immunization or inflammation. The final prognosis of patient A was much better. The proportions of BMMNCs involved in subpopulation 2 and subpopulation 4 from patient A were higher than those from patient B [47.00% (1,431/3,045) versus 29.28% (882/3,012); 5.88% (179/3,045) versus 3.85% (116/3,012)]. Conclusions:The BMMNCs from elderly patients with hip fracture can be divided into subpopulations by scRNA-Seq. Some of the subpopulations may be related to regulation of immunization or inflammation, which may affect the post-injury immune inflammatory state and prognosis of the patients.

Impact of low level viremia on the antiviral effect of human immunodeficiency virus/acquired immunodeficiency syndrome patients received anti-retroviral therapy / 中华传染病杂志

Objective:To investigate the impact of low level viremia (LLV) on the prognosis of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients received anti-retroviral therapy (ART).Methods:From January to December 2015, the HIV/AIDS patients with LLV received ART over one year were recruited in Guangzhou Eighth People′s Hospital, Guangzhou Medical University (LLV group). Patients with viral load (VL) less than 50 copies/mL were matched at ratio of 1∶1 according to gender, age and the transmission route were included in the control group (suppression group). The LLV group was divided into three subgroups according to VL (LLV-1 subgroup was 50-200 copies/mL, LLV-2 subgroup was 201-400 copies/mL, and LLV-3 subgroup was 401-1 000 copies/mL). The influence of LLV on the antiviral response during the following three years was investigated.The Wilcoxon signed rank test, Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:One hundred and thirty-seven patients were enrolled in the LLV group, of whom 111 were males and 26 were females, with age of (39.5±13.5) years old. At the same time, 137 patients were included in the suppression group. There were 93 cases in LLV-1 subgroup, 25 cases in LLV-2 subgroup and 19 cases in LLV-3 subgroup. There were no significant differences in the CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte counts ratios between LLV group and suppression group before ART (both P>0.05). During the three-year follow-up, the cumulative number of viral failures in LLV group (7.3%(10/137)) was significantly higher than that in the suppression group (1.5%(2/137)) ( χ2=5.578, P=0.018). Virological failure occurred in eight patients (8.6%) in the LLV-1 subgroup, two patients (8.0%) in the LLV-2 subgroup, and no patients in the LLV-3 subgroup. There was no statistical significance in the incidence of virological failure among all the subgroups ( P>0.05). At one, two, three years follow-up, the CD4 + T lymphocyte counts increased in both LLV group and suppression group without statistical differences (all P>0.05), and the CD4 + /CD8 + T lymphocyte counts ratios in each LLV group were lower than that in the suppression group ( Z=-3.183, -2.094 and -2.312, respectively, all P<0.05). At one, two, three years follow-up, There were no significant differences in CD4 + /CD8 + T lymphocyte counts ratios among the LLV-1, LLV-2 and LLV-3 subgroups (all P>0.05). Conclusion:HIV/AIDS patients with LLV having received ART over one year are more likely to develop virological failure and delay the recovery of immune function, which requires early relevant interventions.

Research progress in crescent fracture-dislocation of pelvis / 中华创伤杂志

The crescent fracture-dislocation of pelvis (CFDP), also known as sacroiliac joint fracture dislocation, is the posterior iliac wing crescent fracture result from lateral compression force with associated sacroiliac joint dislocation. CFDP accounts for about 12% of the pelvic injury. At present, Day classification has been widely used in clinic. With the development of minimally invasive treatment of pelvic fracture, fine classification, closed reduction and precise screw placement are still the difficulties for clinicians. The authors review the applied anatomy, injury mechanism, classification, diagnosis and treatment of CFDP in order to provide reference for clinical diagnosis and treatment of CFDP.

Clinical characteristics of forty-four cases of acute HIV-1 infection / 中华实验和临床病毒学杂志

Objective@#To investigate the clinical, immunological and virological characteristics of HIV-1 infected patients in the acute phase, for the sake of improving the diagnosis of acute infection with HIV-1.@*Methods@#We retrospectively analyzed the clinical manifestation and laboratory data of patients with acute HIV-1 infection who were admitted to the Center of Infectious Diseases, Guangzhou Eighth People’s Hospital from January 2012 to June 2017.@*Results@#Forty-four patients were enrolled into the study, 86.4% of them were male. 59.1% patients were homosexually transmitted. Clinical symptoms and signs mostly consisted of fever (84.1%), lymphadenopathy (56.8%) and so on, while 15.9% patients had central nervous system symptoms. Most common opportunistic infection included lung infection (50.0%) and oropharyngeal candidiasis (22.7%). Leucopenia (10 patients, 22.7%), and decreased CD4+ T cell count (267.5 cells/μl), inverted CD4+ /CD8+ ratio (86.4%) was mostly seen. Compared to patients who had HIV RNA load less than 6 lg copies/ml, the group of patients who had HIV RNA load more than 6 lg copies/ml had lower levels of CD4+ T cells (t=-3.724, P=0.001).@*Conclusions@#Patients with acute HIV infection have many different kinds of clinical symptoms and can be accompanied by opportunistic infection, and with high viremia.

Analysis on variation characteristics of HIV-1 Gp120 sequences in men who have sex with men in Guangzhou / 中华实验和临床病毒学杂志

Objective@#To analyze the variation characteristics of HIV-1 Gp120 sequences in men who have sex with men (MSM) in Guangzhou.@*Methods@#Plasma samples were collected from HIV-1 infected MSM before antiretroviral treatment. Viral RNA was extracted from plasma. Gp120 gene sequences were amplified by reverse transcription and nested-PCR using specific primers. Phylogenetic tree, length polymorphism, amino acid characteristics of V3 loop, co-receptors and signature amino acids were analyzed.@*Results@#The phylogenetic tree were divided into 4 clusters, and the most prevalent subtypes were CRF07_BC (34/61, 55.74%) and CRF01_AE (24/61, 39.34%). Majority of HIV-1 Gp120 sequences had 496-515 amino acids. Among five hypervariable regions, the V1 region had the highest levels of length polymorphism and V3 region had the lowest. The top four peptide of V3 loop were GPGQ (56/58, 96.55%). Most of the co-receptors HIV-1 strains used was CCR5(50/58, 86.21%)according to four methods of comprehensive prediction. There are four signature amino acids in CRF01_AE subtype strains, and the frequency of occurrence was 0.75-0.83; there are eight signature amino acids in CRF07_BC subtype strains, and the frequency was 0.74-0.94.@*Conclusions@#The length of Gp120 sequences in MSM in Guangzhou has a high polymorphism. The top four peptide of V3 loop, co-receptor and signature amino acid of V3 ring have formed unique patterns.

Analysis of antigen phenotypic epitopes variation in HBV Pre-S/S region in HIV/HBV co-infected patients / 中华实验和临床病毒学杂志

Objective@#To analyze the characteristic mutations of epitopes in HBV Pre-S/S region in HIV/HBV co-infected patients’ peripheral blood to provide basic data for studying the pathogenesis of HIV/HBV co-infection.@*Methods@#The chronic hepatitis B infected patients admitted to the Infectious Disease Center of the Eighth People′s Hospital of Guangzhou from January 2009 to December 2011 were enrolled into HIV/HBV co-infected group and HBV mono-infected group according to the result of HIV antibody detection respectively before treatment. HBV DNA in serum was extracted and Pre-S/S region of HBV DNA was amplified by nested-PCR. After sequencing of the obtained PCR products (direct sequencing), ContigExpress software was used for sequence splicing and BioEdit software was used for sequence alignment. With reference to the standard sequence of the matched genotype HBV, mutants of HBV Pre-S/S region in HIV/HBV co-infected group and HBV mono-infected group were analyzed respectively. Statistical analysis was performed by chi-square test with SPSS19.0 statistical analysis software.@*Results@#HBV Pre-S/S fragments were successfully amplified from 150 patients, including 90 cases of HIV/HBV co-infected group and 60 cases of HBV mono-infected group, with matched gender, age, genotype, HBeAg status, alanine aminotransferase (ALT), aspartate aminotransferase (AST). The result of analyzing mutants of HBV Pre-S/S region indicated that the incidence of mutation in all epitopes for cytotoxic T cells (CTL cells) was higher in the HIV/HBV co-infected group, and Pre-S2 aa1-15 epitope was significantly higher (χ2=6.964, P=0.008). The incidence of deletions in PreS2 aa1-15 epitope in HIV/HBV co-infected group (11.1%) was higher than HBV mono-infected group (3.3%) (χ2=2.959, P=0.085). In the B cell epitopes, the incidence of mutations in Pre-S2 aa1-26 in the HIV/HBV co-infected group was significantly higher than HBV mono-infected group (χ2=6.924, P=0.010), and there was no statistical significance between two groups in other B cell epitopes. No differences in helper T cell (Th cell) epitopes were found between the two groups.@*Conclusions@#Co-infection with HIV increased the CTL cell epitopes’ mutations in the HBV Pre-S/S region, especially the 5′ end epitope mutations in Pre-S2 region, which indicated that HBV mutation is related to the host immune status, and showed guiding information for further study on the pathogenesis of HIV/HBV co-infection

Mechanism of NLRP3/IL-1β pathway in the progression of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To explore the mechanism of action of nucleotide-binding oligomerization domain-like receptor 3(NLRP3)/interleukin-1β(IL-1β)pathway in proliferative diabetic retinopathy.<p>METHODS: Totally 49 cases(49 eyes)of proliferative diabetic retinopathy(study group)and 41 cases(41 eyes)of idiopathic macular hole(control group)in ophthalmology department of our hospital from September 2015 to March 2018 were selected. The expression of NLRP3, the levels of reactive oxygen species(ROS), malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in proliferative epiretinal membrane and macular epiretinal membrane were measured. The concentrations of IL-1β and interleukin-18(IL-18)in the vitreous of the two groups were also determined. <p>RESULTS: The positive expression rate of NLRP3 protein in the study group was significantly higher than that in the control group(90% <i>vs</i> 5%, <i>P</i><0.05). The concentration of IL-1β and IL-18 in the vitreous of the study group was significantly higher than that in the control group \〖(30.84±7.15)<i>vs</i>(4.63±0.92);(97.61±15.73)pg/mL <i>vs</i>(52.07±11.38)pg/mL, <i>P</i><0.05\〗. The levels of ROS and MDA of the study group were significantly higher than those of the control group(<i>P</i><0.05). The activity of SOD in the retina of the study group was significantly lower than that of the control group(<i>P</i><0.05).<p>CONCLUSION: NLRP3 and IL-1β are highly expressed in proliferative diabetic retinopathy. The NLRP3/IL-1β pathway can up-regulate the expression levels of inflammatory and oxidative factors and promote disease progression.

Synthesis and anti-inflammatory activity of novel isobutyl benzophenone derivatives / 药学学报

Twenty target compounds were synthesized by the reduction reaction of HUANG Minglong and Friedel-Crafts acylation reaction in this study. The inhibitory effects of the new compounds were tested on NO production in LPS-induced mouse macrophage RAW264.7 cells, a cellular inflammation model. The structure-activity relationships were discussed. The structures of target compounds were confirmed by ESI-MS, 1H NMR and 13C NMR. In vitro activity experiments showed that 18 compounds had certain anti-inflammatory effects at the concentration of 40 μmol·L-1, of which 9a, 8b, 7c and 9c showed strong anti-inflammatory activities, and IC50 of 7c and 9c were comparable to the positive control drug ibuprofen.

Semen quality and HIV RNA level in HIV/AIDS male patients after treated by highly active antiretroviral therapy / 中华男科学杂志

<p><b>Objective</b>To evaluate the semen quality of the HIV/AIDS male patients after treated by the highly active antiretroviral therapy (HAART) and their potential of transmitting HIV/AIDS and provide some evidence for this cohort of males who wish for parenthood.</p><p><b>METHODS</b>We collected semen samples from 20 HIV/AIDS male patients who had been treated by HAART for over 6 months and wished for parenthood. We examined sperm concentration, viability and total motility and the percentage of morphologically normal sperm (MNS) using the computer-assisted semen analysis system, measured the HIV-1 RNA loads in the semen by the Cobas Amplicor Monitor test, and counted CD4+ T cells in the peripheral blood by flow cytometry.</p><p><b>RESULTS</b>The patients were aged 25－40 (30.7 ± 5.05) years. After treated by HAART for 6－26 (14.24 ± 12.26) months, the count of blood CD4+ T cells was significantly increased (341－1 058 ［535.76 ± 212.021］ /μl) in comparison with the baseline (226－965 ［422.38 ± 200.86］ /μl). Compared with the normal value, the semen volume was increased except in 1 case (≥2 ml) while total sperm motility was decreased in 13 cases (≥40%), and so were sperm concentration in 2 cases (≥15 × 106 / ml), sperm viability in 5 (58%), the percentage of progressively motile sperm in 18 (≥32%), and the percentage of MNS in 6 (≤4%). HIV-1 RNA in the peripheral blood was <20 copies/mL in all the cases and that in the seminal plasma was also <20 copies/ml in 18 cases but >20 copies/mL in the other 2 (［4.70 × 101］ and ［2.2 × 102］ copies/ml, respectively). Of the 4 couples that had sex without protective measures for over 6 months, all the 4 female partners exhibited negative HIV antibodies in regular follow-up examinations and 1 achieved spontaneous pregnancy and healthy birth, with negative HIV-1 RNA in both the mother and the baby.</p><p><b>CONCLUSIONS</b>The HIV RNA level is higher in the semen than in the blood of the HIV/AIDS male patients after HAART, which indicates the potential risk of their semen transmitting HIV/AIDS to their female partners. Their sperm concentration and total sperm motility are lower than the normal value, which suggests a decreased fertility.</p>

Characterization and primary resistance mutations in gag-pol gene of human immunodeficiency virus-1 CRF07_BC strain in Guangdong Province / 中华传染病杂志

Objective To investigate the genetic variations of gag-pol gene in human immunodeficiency virus-1(HIV-1) CRF07_BC strain in Guangdong Province.Methods From February to September in 2015,plasma samples of 78 cases with HIV 1 CRF07_BC infection in Guangdong were collected before antiretroviral treatment.Viral RNA was extracted from plasma.Gene (gag and pol) sequences were amplified by reverse transcriptase and nested-PCR using specific primers.Phylogenetic tree,genic dispersion rate,nucleotide polymorphism,selection pressure and variation characteristics were analyzed.Results The main transmission route of the enrolled patients was homosexual transmission (80.77％,63/78).The gag pol gene phylogenetic tree was divided into two sub-clusters.The strains from different transmission routes were not in cluster.The average genetic dispersion rate and average entropy of gag gene were both higher than those of pol gene.The average genetic dispersion and average entropy of p17 and p6 regions of gag gene were both higher than those of p24.The average genetic dispersion and average entropy of pol gene were higher than those of rt region.The average ds/dn values of gag and pol genes were greater than one.Compared with the common HIV-related antigenic epitopes (A2,A11,B39,B60,Cw1,Cw3,Cw8),the cytotoxic lymphocyte (CTL) epitope mutations in the P17 region were more in the consensus of GAG region than those in the P24 region.The epitope conserved rates were 26.92％,0,1.28％,0,96.15％,82.05％,84.62％ and 98.72％,respectively.The drug resistance rate of pol gene was 2.56％ (2/78).Conclusions The gag and pol genes of CRF07_BC strain in Guangdong are all mutated.Diversity of gag gene is greater than that of pol gene,and gag gene variation is mainly in p17 and p6 regions.gag and pol genes are both affected by negative selection pressure.P17 protein CTL epitope variability is greater than P24 protein epitope.The prevalence of drug resistance mutation is lower than the threshold.It's important to monitor the spread of drug-resistant strains.

Discussion on optimal duration of pegylated interferon α combined with ribavirin for chronic hepatitis C in HIV-infected patients / 中华肝脏病杂志

Objective@#To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients.@*Methods@#A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4+ cell counts: A1 subgroup, 79 cases, CD4+ counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4+ counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4+ counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4+ counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ 2 test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests.@*Results@#There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05).@*Conclusion@#HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4+ counts 200 cells/ μl.

IL-17D regulates recruitment of lung NK cells and promotion of Astragalus membranaceus / 中国免疫学杂志

Objective:To investigate the role of IL-17D to regulate the recruitment of lung NK cells and the effects of Astragalus membranaceus on IL-17D.Methods:The lung metastasis of tumor model was established by injecting B16 melanoma cells through caudal vein.After being treated with IL-17D or Astragalus membranaceus respectively,the expression of IL-17D and NK cells in lung was detected by flow cytometry and RT-PCR.Results:The production of IL-17D and the content of NK cells in the lung tumor me-tastasis model were dramatically decreased.After treatment with IL-17D,the content of NK cells in lung was significantly increased and the lung tumor foci were decreased.Along with up-regulated recruitments of NK cells,CXCL9 and IL-15,which support NK cell recruitments and maintain survival,were significantly increased.Astragalus inhibited lung tumor developments in lung by increasing the IL-17D expression and up-regulated the lung NK cell content.Conclusion: IL-17D can regulate the lung recruitment of NK cells.Astragalus mongholicus can enhance the capacity of NK cell recruitment and promote anti-tumor immune effects by up-regulating the expression of IL-17D.

Efficacy of EX - PRESS combined with amniotic membrane implantation for open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the efficacy of EX-PRESS combined with amniotic membrane implantation for open angle glaucoma. METHODS:The data of 43 eyes of 43 patients with open angle glaucoma were enrolled from January 2014 to January 2017. The patients were randomly divided into amniotic group and mitomycin (MMC) group. All cases received EX-PRESS combined with amniotic membrane implantation (amniotic group) or with intraoperative application of mitomycin (MMC group). The early postoperative anterior chamber formation, filtering bleb, intraocular pressure ( IOP) and complications were analyzed. RESULTS: The intraocular pressure of the two groups were significantly lower at 1wk,1 and 6mo after operation than those before operation (P<0. 05). There was no significant difference in the best corrected visual acuity in the two groups at 1wk after operation compared with before operation(P>0.05). At 1 and 6mo postoperatively, the rate of functional bleb formation was 91% and 73% in amniotic group, and they were 90% and 86% in MMC group, respectively, the difference between the groups were not statistically significant (all P>0.05). At 1 and 6mo postoperatively,the total success rate was 95%,86% in amniotic group, and they were 95%, 90% in MMC group, respectively, the difference between the groups were not statistically significant (all P>0. 05). At 1wk postoperatively, the incidence of shallow anterior chamber was 9% in amniotic group and 33% in the MMC group, the difference was statistically significant (P <0 05). At 1mo postoperatively, the incidence of bleb leakage was 5% in amniotic group and 29% in MMC group, the difference was statistically significant (P <0 05). At the end of follow-up, there were 4 eyes of thin-wall bleb in MMC group and no cases in amniotic group. CONCLUSION: EX - PRESS combined with amniotic membrane implantation for open angle glaucoma is good on lowering intraocular pressure with less complications than the combination of MMC.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)resistance-related gene mutations among AIDS patients with antiviral treatment failure in Guangdong province 2015 / 中华临床感染病杂志

Objective To investigate the prevalence and characteristics of non-nucleoside reverse transcriptase inhibitors (NNRTIs)resistance-related gene mutations among the AIDS patients with virological suppression failure in Guangdong Province 2015.Methods Plasma samples from AIDS patients receiving highly active antiretroviral therapy for more than one year with viral loads > 1000 copies/mL from Guangdong province (except Shenzhen)were collected from January to December 2015.Total 612 HIV-1 gene fragments were amplified from plasma samples using self-developed lab method.Sub-genotypes were determined by phylogenetic tree according to the sequences,NNRTIs resistance-related mutations were determined in Stanford University HIV-1 Drug Resistance Database. The NNRTIs-resistance, the relationships of NNRTIs resistance-related mutations with baseline CD4 +T lymphocyte counts,transmission routes,antiviral regimens and HIV-1 genotypes were analyzed.SPSS 17.0 software was used to analyze the data.Results In 612 patients with virological suppression failure,the main NNRTIs resistance-related mutations were K103 (26.80%),Y181 (14.71 %),V179 (13.73%),G190 (11 .44%) and V106 (10.62%).The susceptibility rate of 310 patients (50.65%)to NNRTIs had changed,the highly resistant rate to nevirapine was 49.51 %,which was higher than that of efavirenz (43.14%),etravirine (5.56%) and rilpivirine (12.25%),respectively,and the differences were statistically significant (χ2 =5.00,296.3 and 198.0,all P 200 cells/μL was lower than that in those with baseline CD4 +T lymphocyte counts <200 cells/μL (χ2 =17.93,P <0.01 );the incidence rate of drug resistance was lower in intravenous drug abusers than that of sexually transmitted patients (χ2 =44.21 ,P <0.01 );while the incidence of drug resistance in patients receiving NVP-containing regimens was higher than that in those receiving EFV-containing regimens (χ2 =8.93,P <0.01 ),and the incidence rate was higher in patients with CRF01 _AE than that in those with CRF07_BC and CRF08 _BC (χ2 =8.46 and 8.47,P <0.01 ).Conclusions The results suggest that compliance education and follow-up should be strengthened in patients with high baseline CD4 +T lymphocyte counts and intravenous drug users,and patients with liver diseases should avoid using drugs containing NVP regimens.

The gene polymorphisms of drug targets in Pneumocystis jiroveci isolates / 中华传染病杂志

Objective To investigate gene polymorphisms of drug targets and mutations associated with drug resistance in Pneumocystis jiroveci (P.jiroveci) isolates.Methods Among 148 samples isolated from human immunodeficiency virus (HIV)infected patients with pneumonia in Guangdong,mitochondrid larg subunit rRNA (mtLSUrRNA) gene was amplified from 51 samples.Dihydropteroate synthase (DHPS),dihydrofolate reductase (DHFR) and Cytochrome b (CYB) genes of P.jiroveci were detected by gene sequencing,and compared with the reference sequences in GenBank to evaluate gene polymorphisms.Results P.jirovecii DHPS,DHFR and CYB genes were all successfully amplified from 51 samples.For DHPS gene,48 (94.1％) were wild-type and 3 (5.9％) had gene mutation associated with drug resistance.For DHFR gene,30 were wild-type,and 21 had a synonymous mutation at position 312,and 1 nonsynonymous mutation at position 188.There were no mutations associated with drug resistance.For CYB gene,polymorphisms of were detected at 5 sites,4 of which were synonymous mutations,1 was non-synonymous mutation.No mutation associated with drug resistance was found.Based on the gene polymorphism of CYB6,the strains can be classified into 6 genotypes,and 2 were first detected,including 25 CYB1,13 CYB2,2 CYB5,4 CYB8,as well as newly detected 4 CYB10 and 3 CYB11 strains.Conclusions The mutations associated with drug resistance in P.jiroveci isolates in Guangdong remain uncommon.CYB gene shows gene polymorphisms and can be selected as one of targeted genes for multilocus sequence typing.

Effect of acupuncture plus swallowing disorder therapeutic apparatus on deglutition disorder caused by early stroke / 中国基层医药

Objective To observe the effect of acupuncture plus thunder fire moxibustion plus deglutition training plus VitalStim electrical stimulation on patients with deglutition disorder of early stroke.Methods 80 patients with deglutition disorder of early stroke were randomly divided into treatment group and control group,40 cases in each group.The treatment group was treated with acupuncture plus thunder fire moxibustion plus deglutition training plus VitalStim electrical stimulation,while the control group was only treated with deglutition training.The therapeutic effects of all patients were assessed by using drinking experiment before therapy and twenty times after therapy. Results The total effective rate of the treatment group was 97.5%,which was significantly higher than 82.5% of the control group,the difference was statistically significant(χ2 =12.50,P <0.05).Watian integration of the two groups were decreased after treatment,the difference was significant(t =5.606,9.056,all P <0.05),which of the treatment group was significantly lower than the control group,the difference was statistically significant(t =3.044,P <0.05). The lung infection rate and malnutrition rates in the control group were 10.0% and 20.0%,which were significantly higher than those in the treatment group(2.5% and 5.0%),the differences were statistically significance(χ2 =4.80, 10.29,all P <0.05).Conclusion Acupuncture plus thunder fire moxibustion plus deglutition training plus VitalS-tim electrical stimulation are beneficial to the recovery of swallowing functions to early swallowing disorder in patients and could avoid the incidence of aspiration pneumonia and malnutrition.

Determination of seven yellow pigments illegally added into Chinese materia medica by HPLC-MS / 中草药

Objective: To establish a rapid method for the simultaneous determination of seven yellow pigments (tartrazine, sunset yellow, brilliant yellow, orange II, auramine O, astrazon orange G, and basic orange) which were illegally added into Chinese materia medica (CMM). Methods: The sample was extracted with ultrasonic by 70% ethanol, separated on a reversed phase C18 chromatographic column by gradient elution using a mobile phase made up of acetonitrile and 0.05 mol/L ammonium acetate solution, and then detected by diode array detector in the wavelength of 432 nm and mass spectrometry detector with ESI+ ion source. Results: Under the condition of the above chromatography and mass spectrometry, the separating degree, specificity, and durability of the seven yellow pigments were good. RSD of precision was between 0.4%-1.8%. Above pigment solution was stable in 24 h and RSD < 1.9%. The recovery rates of accuracy were between 95.1%-102.9%. The limits of detection (LODs) were in the range of 2-31 μg/kg, and the RSD of repeatability was in the range of 0.3%-1.4%. Auramine O was detected in three batchs of CMM for sale. Conclusion: This method is simple, rapid, reproducible and has high sensitivity, which can be used for the determination of seven yellow pigments illegally added into dyed CMM, and it can provide the reference or help for relative company and State Food and Drug Administration in controlling the quality of CMM.