Prevalence and risk factors for bone mineral density changes in antiretroviral therapy-naive human immunodeficiency virus-infected adults: a Chinese cohort study / 中华医学杂志(英文版)

BACKGROUND@#Studies have reported that low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected patients; however, the factors that contribute to HIV-related BMD changes are yet to be fully understood. Due to the application of dual X-ray absorptiometry (DXA) among a select group of hospitals only, the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China. Thus, the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy (ART)-naive HIV-positive patients in China.@*METHODS@#The assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients. Demographic and clinical data, as well as results of fasting blood tests were obtained from patients. Further, all patients underwent DXA scans to determine BMD, which was then used to classify patients with osteopenia/osteoporosis. The risk factors of reduced BMD were then evaluated using binary logistic regression.@*RESULTS@#Among the 156 ART-naive HIV-infected participants, osteopenia and osteoporosis were diagnosed in 48.7% (76/156) and 4.5% (7/156) of patients, respectively. The lumbar spine was most likely to have reduced BMD (49.4% [77/156]), and the proportion of osteopenia in the left hip (32.7% [51/156]) was higher than in the right hip (24.4% [38/156]). In the lumbar spine, bone loss rate in the L1 section (60.9% [95/156]) was the most significant (L2, 53.2% [83/156]; L3, 45.5% [71/156]; L4, 52.6% [82/156]). Further analysis showed that, compared with the neck (26.9% [42/156] in the left, 18.6% [29/156] in the right) and the interior (15.4% [24/156] in the left, 13.5% [21/156] in the right), the trochanter had the greatest probability of reduced BMD (46.2% [72/156] in the left, 28.8% [45/156] in the right). In the risk factor analysis, low body mass index (BMI: <18.5 kg/m2) was positively associated with reduced BMD (Exp (B) = 39.743, 95% confidence interval: 3.234-488.399, P = 0.004), and was specifically positively correlated with BMD values at three sites (r = 0.335 at right hip, r = 0.327 at left hip, r = 0.311 at lumbar spine).@*CONCLUSION@#Reduced BMD was found in the majority of ART-naive HIV-infected patients and BMI was identified as an additional risk factor for reduced BMD. Our results show that BMD reduction was simultaneously present in the left hip, right hip, and lumbar spine among nearly one fifth of patients. Our work highlights the importance of closely monitoring BMD in ART-naive patients and provides a foundation for the clinical intervention of bone demineralization in them.

Study on mechanism of down-regulation of SLP-2 gene expression on proliferation and apoptosis of glioma cells / 中国免疫学杂志

Objective:To investigate the effect of downregulation of SLP-2 gene expression on proliferation and apoptosis of brain glioma cells.Methods:The targeting siRNA sequence of SLP-2 transfected U251 human glioma cells,blank group (without any cell treatment)and negative control group (cell transfected nonsense siRNA sequence)were set,Western blot was used to detect the expression of SLP-2,Bcl-2,Bax,Notch1,Hes1 protein after transfected 48 h;cell proliferation was detected by CCKg;cell apoptosis was detected by flow cytometry.Results:The protein expression of SLP-2 in negative control group had no significant difference with the control group (P＞0.05),and the expression of SLP-2 protein in SLP-2 knock down group was significantly lower than control group (P＜0.05);cell survival rate,apoptosis rate,mRNA expression of IL-6,TNF-α and Bcl-2,Bax,Notch1,Hes1 protein expression in the negative control group and the blank group had no significant difference (P＞0.05),cell survival rate,mRNA expression of IL-6 and TNF-α and the expression of Bcl-2,Notch1,Hes1 protein in SLP-2 knock down group was significantly lower than control group,the apoptosis rate and the expression of Bax protein was significantly higher than control group (P＞0.05).Conclusion:Downregulation of SLP-2 gene expression can significantly inhibit the proliferation and induce apoptosis of glioma cells,down regulate the expression of inflammatory cytokines IL-6 and TNF-α,and the mechanism is related to the inhibition of Notch1 signaling pathway.

Specific causes of death among 381 AIDS patients who died in hospitals / 中华流行病学杂志

<p><b>OBJECTIVE</b>In this study, researchers investigated the demographic and clinical characteristics of AIDS patients who died in hospitals, analyzed the specific causes of death, and looked for the correlation between specific cause of death and their clinical characteristics.</p><p><b>METHODS</b>Data of clinical characteristics of patients and their specific causes AIDS of death who died in the seven hospitals from 2009 to 2010 were collected retrospectively. All the specific causes of death were classified according to the Cause of Death (CoDe) project protocol. Univariate analysis and multivariate logistic regression analysis were used to find the association between some categorical variables and the risk for AIDS patients died from AIDS related illnesses.</p><p><b>RESULTS</b>Clinical characteristics and the cause of death of the 381 deceased in seven hospitals in this study were collected. 82.4% were male, with priority as 30-45 years old. 123 (32.3%) death patients had received ART before death. In all death cases, the cause of death of 252 patients (66.1%) were due to AIDS related diseases, with opportunistic infections the most (92.4%). Tubercle bacillus, infection of Penicillium marneffei and Pneumocystis jiroveci were the three leading causes of opportunistic infection deaths. Of 129 patients who died of non-AIDS related disease, non-AIDS infection (29.5%), hepatitis (22.5%), and non-AIDS malignancy(10.1%)were the first three causes of death. The cause of death in patients who had injecting drug use behavior within one year, had not received ART or not long enough, with opportunistic infections, without hepatitis, with the last low CD4 cell counts before death etc. were tend to due to AIDS related disease.</p><p><b>CONCLUSION</b>Opportunistic infections, non-AIDS related infections and hepatitis were the three leading causes of death in this study. The duration of time on ART had impact on the patient's cause of death. The HIV infected patients who had received ART before death had more risk to die of non-AIDS related disease, compared to patients who had not. The longer time they had accessed to ART, the less likely they would die on non-AIDS related illnesses.</p>

Assessment on depressive status and the therapeutic effects of highly active antiretroviral therapy among anti-HIV-1(+) population / 中华流行病学杂志

<p><b>OBJECTIVE</b>To assess the depressive status and its influence on Chinese HIV-1(+) population, and how it was influenced by highly active antiretroviral therapy (HAART) and the CD4(+) T cell count.</p><p><b>METHODS</b>Anti-HIV-1(+) patients (age between 18 and 65 years old) who had met the criteria to commence the anti-HIV treatment but had not yet started, were selected from the Beijing Ditan Hospital between March 2011 and June 2012. BDI-II (Beck Depression Inventory) and a self-designed questionnaire were used to evaluate the baseline and the status of 48 weeks post the HAART treatment. Statistically, t test and the Wilcoxon rank sum test were used to compare the BDI scores under different conditions and before/after the HAART.</p><p><b>RESULTS</b>(1) Of 100 subjects: male to female ratio was 99:1; the average age was 31.37 ± 5.58 years; the average education background was of 13.13 ± 3.51 years; the unemployed percentage was 4%; time before being identified as anti-HIV-1(+) was 5.0 (1.0 - 21.0) months; the percentage being infected through homosexual contact was 83%. The baseline BDI score was 6.0 (3 - 10.25). (2) There was no significant difference (P > 0.05) in BDI score between those subjects having had education less or more than 12 years; the BDI score of patients whose anti-HIV-1(+) was significantly higher (P < 0.05) among those discovered within the past 6 months than those more than 6 months. The BDI score of patients whose baseline CD4(+) T cell count below 200 cells/µl was significantly higher (P < 0.05) than those with baseline CD4(+) T cell count greater than 200 cells/µl. The CD4(+) T cell count was significantly high (P < 0.001) after 48 weeks of anti-viral treatment, but the BDI score was not significantly different (P > 0.05). There was no significant change (P > 0.05) in the proportion of patients with different degrees of BDI score before and after 48 weeks of antiviral treatment.</p><p><b>CONCLUSION</b>Depression in HIV patients was most overt in the first six months when they were aware of the infection. The degree of depression was more severe in patients with baseline CD4(+) T cell count less than 200 cells/µl with improvement of immunity after the HAART did not alleviate the level of depression.</p>

Multi-centered, randomized controlled clinical study on Chinese medicine formula particles for hyperlipidaemia associated with highly active antiretroviral therapy / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect and safety of Xiaozhi particles, integrated taohong Siwu tang and Erchen tang and Xuezhikang capsule in treating hyperlipidaemia (HLP) associated with highly active antiretroviral therapy (HAART).</p><p><b>METHOD</b>In the multi-centered, randomized controlled clinical study, 180 hyperlipidaemia associated with highly active antiretroviral therapy cases were divided into the treatment group treated by Xiaozhi particles, integrated Taohong Siwu tang and Erchen tang, and the control group treated by Xuezhikang capsule. The treatment course was 12 weeks. The total cholesterol (Tch), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein(HDL) were observed.</p><p><b>RESULT</b>After 12 weeks, compared with Xuezhikang capsule, the change difference of Tch, LDL, HDL in the Chinese traditional medicine formula groups of patients is significant (P < 0.05), the change of the TG has no significant difference. The effect of Tch, LDL in Xuezhikang capsule groups is better than in traditional Chinese medicine formula group,but the effect of HDL in traditional Chinese medicine formula group is better than in Xuezhikang capsule groups.</p><p><b>CONCLUSION</b>Integrated Taohong Siwu tang and Erchen tang, Xiaozhi particles and Xuezhikang capsule can be used to control the hyperlipidaemia associated with highly active antiretroviral therapy as one of the main Chinese native medicine preparation.</p>

Different plasma levels of interleukins and chemokines: comparison between children and adults with AIDS in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The immunological differences between children and adults with AIDS in China are not well documented. Th1/Th2 cytokines and chemokines are two types of immune factors intimately involved in disease progression of HIV-1 infection. This study aimed to identify changes in plasma levels of Th1/Th2 cytokines inerleukin (IL)-18, IL-16, IL-10 and chemokines regulated on activation, normal T cell expressed and secreted (RANTES), stromal cell-derived factor-1 (SDF-1) and monocyte chemoattractant protein-1 (MCP-1) in HIV-1-infected children and adults in China.</p><p><b>METHODS</b>Seventy-five children with AIDS and 35 adult AIDS patients were recruited and clinical data were collected. CD4(+) T lymphocyte counts were measured by flow cytometery and plasma HIV RNA levels were measured by quantitative RT-PCR. Plasma levels of IL-18, IL-10, IL-16, RANTES, MCP-1, SDF-1alpha and SDF-1beta were quantified by enzyme-linked immunosorbent assay. The levels of beta2-microglobulin (beta2-MG) and soluble Fas (sFas) were measured to validate the level of humoral and cellular immune activation.</p><p><b>RESULTS</b>The mean levels of all cytokines in pediatric and adult AIDS patients were significantly higher than in their healthy controls (P < 0.01). The mean levels of these cytokines were higher in pediatric patients than in adult patients (P < 0.05, except for SDF-1alpha and beta2-MG). Some of the cytokine levels in patients younger than 6 years old was higher than in older children and adults with AIDS (IL-10, IL-18, SDF-1alpha, MCP, RANTES and sFas, P < 0.05). Levels of IL-18, IL-10, RANTES and beta2-MG of pediatric patients increased as the levels of viral load increased (P < 0.05).</p><p><b>CONCLUSIONS</b>Abnormal immune activation can be measured in Chinese pediatric and adult patients with AIDS, and is higher in children than in adult patients. The cytokines levels coincide with disease progression of AIDS, but have no direct relationship with total CD4(+) T cell count.</p>

An ambispective cohort study of the natural history of HIV infection among former unsafe commercial blood and plasma donors / 中华流行病学杂志

<p><b>OBJECTIVE</b>Discussing the natural history and the influencing factors of HIV infection among former commercial blood and plasma donors engaged in unsafe blood donation practices in China.</p><p><b>METHODS</b>Using ambispective cohort study, with data obtained from ten counties (districts) from six provinces in the National AIDS Control Demonstration Area. HIV/AIDS cases were found and confirmed prior to July 24, 2006 being former commercial blood. Plasma donors were selected and data regarding infection, incidence, death, and influencing factors was collected. Analysis was performed using SPSS 12.0 statistical analysis software.</p><p><b>RESULTS</b>(1) In 7551 cases of HIV infection, there were 6533 typical progressors (86.52%, 4757 cases of AIDS), 108 rapid progressors (1.43%), 910 long-term non-progressors (12.05%) with 4865 cases progressed to AIDS (64.43%). The median incubation period for HIV progression to AIDS was nine years (95% CI:8.96-9.04). (2) According to data, from a total of 1157 AIDS cases without ARV therapy (23.78% of total AIDS cases), there were 283 confirmed AIDS-related deaths, of which the median survival time was 6 months (95% CI:4-7) and the two and three year fatality rates were 95% and 99%, respectively. (3) The duration of HIV incubation period was irrespective to gender and age at the time of HIV infection (P > 0.05). Length of survival for untreated AIDS showed correlation to gender (P < 0.05) but no correlation with culture, marital status or age at the time of diagnosis of AIDS (P > 0.05).</p><p><b>CONCLUSION</b>Compared with the UNAIDS theory regarding slow disease progressors among adults, our study showed a longer AIDS incubation period and shorter outlook for untreated survival, but a similar incubation period for other routes of HIV infection.</p>

Survival analysis of 530 HIV infected former unsafe commercial blood and plasma donors / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate HIV survival time and it's influencing factors among former commercial blood and plasma donors engaged in unsafe blood donation practices in China.</p><p><b>METHODS</b>HIV/AIDS cases from 8 counties (districts) in 4 provinces confirmed prior to January 24, 2006 related with former commercial blood and plasma donors were selected and data regarding infection, AIDS progression, death, and influencing factors were retrospectively collected.</p><p><b>RESULTS</b>In 530 cases of HIV infection, 334 (63.0%) cases had developed AIDS, 168 (50.3%) had received antiretroviral therapy (ART), and 152 (29.0%) had died. For the 530 cases, there was an average (10.1 +/- 1.8) years of observation from time of infection. Among 166 AIDS patients not receiving ART, average survival was 9.1 years (95% CI: 9.1 - 9.4), with an 8 year survival rate of 52.0%. Among 168 AIDS patients receiving ART, average survival was 12.1 years (95% CI: 11.9 - 12.3), with a 12-year survival rate of 80.0%. In 3 years of ART, average survival was longer in the treatment group as compared to the no treatment group with a hazard ratio for death of 12.2. Univariate analysis showed a significant difference (P < 0.05) in AIDS patient average survival based on gender, age, location, ART status, and baseline CD(4)(+) T cells count. Results from multivariate COX-regression showed that highly active ant iretroriral therapy (HAART) was the strongest protective factor for prolonging AIDS patients' survival (HR = 13.3, P = 0.00).</p><p><b>CONCLUSION</b>Although there are many factors influencing AIDS patients survival, intervention with HAART is the principle measure to prolong survival and decrease the risk of death.</p>

Male infertility with severe oligospermatism and azoospermia treated by Bushen Shengjing Decoction combined with intracytoplasmic sperm injection / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the pregnancy promoting effect of Bushen Shengjing Decoction (BSSJD) combined with intracytoplasmic sperm injection (ICSI) in treating male infertility with severe oligospermatism and azoospermia (SOA).</p><p><b>METHODS</b>ICSI were applied on 164 patients, among them, the 82 assigned to the TCM group were treated with additionally by BSSJD before injection for 2-3 months, and the other 82 assigned to the control group received ICSI alone. The density, motility, viability and deformity of sperm; semen level of reactive oxygen species (ROS); number of eggs retrieved, M II eggs and mean transplanted fetus; rates of fertilization, cleavage, available embryo and clinical pregnancy in the two groups were observed and compared.</p><p><b>RESULTS</b>Compared with those in the control group, the density, motility and viability of sperm were higher, the deformity rate and ROS level were lower in the TCM group respectively (P<0.05). Moreover, higher rates of fertilization and clinical pregnancy were also shown in the TCM group (P<0.05).</p><p><b>CONCLUSION</b>BSSJD has the effects of decreasing semen level of ROS and improving the quality of sperm. It is also helpful for the natural fertilization ability of patients with SOA and raise the viability of their sperm to increase the ovarian fertilization rate and clinical pregnancy rate in ICSI cycles.</p>

Effect of traditional Chinese herbs combined with low dose human menopausal gonadotropin applied in frozen-thawed embryo transfer / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess embryo implantation rate (IR) and pregnancy rate (PR) in women who received Bushen Wengong Decoction (BSWGD), a Chinese herbal formula, combined with low dose of human menopausal gonadotropin (hMG) prior to frozen-thawed embryo transfer (FET).</p><p><b>METHODS</b>A total of 262 subjects (674 transferred embryos) who received FET were analyzed retrospectively. In them, 122 women were under 30 years old, 106 between 30 - 35 years and 32 over 35 years. The 85 subjects with normal ovulation were assigned to Group A, the natural menstruation cycling group, on whom no pre-transfer treatment was applied. The other 177 subjects with abnormal ovulation were assigned to Group B, and subdivided, according to the pre-transfer treatment they received, into three groups, Group B1 (50 cases) received BSWGD, Group B2 (58 cases) received hMG and Group B3 (69 cases) received both BSWGD and low dose hMG. The IR and PR of FET in the four groups were compared, and the effect of the embryo cryotime on PR of FET were compared also. Besides, the influencing factors to FET were analyzed.</p><p><b>RESULTS</b>IR and PR were significantly higher in all age sects of Group B3 than those in Group A, showing significant difference (P< 0.05). IR and PR in subjects in age sects of <30 years and > 35 years in group B3 were significantly higher than those in Group B1 ( P<0.05), but no significant difference was shown in the two parameters between Group B 2 and Group B3 (P>0.05). PR in the subjects who received embryos with cryo-time of > 200 days was significantly lower than that in those with cryo-time of < 100 days ( P<0.05). Embryo cryo-time, endometrial thickness, use of BSWGD and use of hMG were of significance in FET ( P 0.05).</p><p><b>CONCLUSION</b>A programmed cycle of BSWGD combined with low dose of hMG could improve the embryo IR and PR of FET. Embryo cryo-time, endometrial thickness, and the use of BSWGD and hMG are of significance for FET.</p>

Pathology of AIDS-related lymphadenopathy and its relationship to expression of CD4 + CD25 + regulatory T cells in lymphoid node tissue / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the pathology of AIDS-related lymphadenopathy and its relationship to the expression and distribution of CD4 + CD25 + regulatory T cells in lymphoid node tissue.</p><p><b>METHODS</b>Totally 22 biopsy and 13 autopsy lymphoid node tissues from HIV-positive patients were examined under microscopy and pathological staging was performed. Specific marker for CD4 + CD25 + regulatory T cells in lymphoid node tissue was detected with anti-Foxp3 monoclonal antibody by immunohistochemistry.</p><p><b>RESULTS</b>Among all the 35 specimens, 5, 4, 14, and 12 specimens were histopathologically staged from 1 to 4, respectively. FoxP3 were detected in all lymphoid node tissues. The distribution of FoxP3-positive lymphocytes were mainly in intermediate zone of follicle and cortical area in stages 1 and 2. The counts of FoxP3-positive lymphocytes remarkably decreased in stages 3 and 4, following depletion of lymphocytes.</p><p><b>CONCLUSIONS</b>CD4 + CD25 + regulatory T cells exist in lymphoid node tissue of patients with HIV infection. Their amounts decrease or deplete along with the progression of AIDS-related lymphadenopathy.</p>

Comparison of immunological profiles between pediatric and adult patients with AIDS in China / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the immunological profiles of pediatric and adult patients with AIDS in China.</p><p><b>METHODS</b>Totally 103 pediatric AIDS patients, 38 adult patients, 88 healthy children, and 72 healthy adults were enrolled. CD4 + T lymphocyte counts were determined by four-color flow cytometer and HIV-RNA levels were measured in EDTA plasma by quantitative reverse-transcription polymerase chain reaction (RT-PCR). Plasma levels of interleukin (IL)-10, IL-16, IL-18, regulated upon activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein 1 (MCP-1), stromal cell-derived factor-(SDF-1) alpha, SDF-1 beta, and macrophage stimulate protein (MSP) were quantified by enzyme-linked immunosorbent assay (ELISA). The levels of beta 2-microglobulin (beta 2-MG) and soluble Fas (sFas) were measured to indicate the activation of immune system.</p><p><b>RESULTS</b>The mean CD4 + T cell count in pediatric patients with AIDS was significantly lower than in healthy children (P < 0.01), as between the adult AIDS patients and healthy adults (P < 0.01). The mean levels of these cytokines in pediatric patients were significantly higher than in healthy children (P < 0.01). The level of MSP in adult patients was significantly lower than in healthy adults and other cytokines were significantly higher (P < 0.01). The mean levels of these cytokines, except SDF1 alpha and beta 2-MG, were significantly higher in pediatric patients than in adult patients (P < 0.01).</p><p><b>CONCLUSION</b>Abnormal immune activation is induced in both pediatric and adult patients with HIV-1 infection. The level of immune activation is higher in pediatric patients than in adult patients.</p>

Effects of traditional Chinese medicine on CD4 + T cell counts and HIV viral loads during structured treatment interruption in highly active antiretroviral therapy / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the impacts of traditional Chinese medicine (TCM) on CD4 + T cell counts and human immunodeficiency virus (HIV) viral loads during the course of structured treatment interruption (STI) in highly active antiretroviral therapy (HAART).</p><p><b>METHODS</b>Nineteen HIV/ADIS patients were treated for 14 months as follows: initiated with zidovudine/lamivudine + efavirdine for 6 months, then discontinued the therapy and treated with TCM instead for 2 months. HAART was then reinitiated for another 3 months, and then discontinued and replaced with TCM for another 3 months. The changes of CD4 + T cell counts and HIV viral loads were measured.</p><p><b>RESULTS</b>During the first STI of HAART, 43.8% of patients had no viral rebounds one month later, and 62.6% had stable or increased immune functions; 18.8% had no viral rebounds two months later, and 43.8% had stable or increased immune functions. Changes of viral loads were not significantly different between these two months (P = 0.097), while CD4 + T cell counts significantly decreased two months later compared with one month later (P = 0.043). During the second STI of HAART, 33.3% of patients had no viral rebounds one month later, and 64.3% had stable or increased immune functions; 13.3% had no viral rebounds 3 months later and 46.6% had stable or increased immune functions. Changes of viral loads had significant difference (P = 0. 017), while CD4 + T cell counts at month 12 elevated significantly compared with the baseline (P = 0.014).</p><p><b>CONCLUSIONS</b>TCM can suppress the viral rebounds during STI-HAART, maintain immune functions. However, this effect may decrease along with the prolongation of STI-HAART.</p>