Associations of phthalates with accelerated aging and the mitigating role of physical activity.

Phthalates are positioned as potential risk factors for health-related diseases. However, the effects of exposure to phthalates on accelerated aging and the potential modifications of physical activity remain unclear. A total of 2317 participants containing complete study-related information from the National Health and Nutrition Examination Survey 2007-2010 were included in the current study. We used two indicators, the Klemera-Doubal method biological age acceleration (BioAgeAccel) and phenotypic age acceleration (PhenoAgeAccel), to assess the accelerated aging status of the subjects. Multiple linear regression (single pollutant models), weighted quantile sum (WQS) regression, Quantile g-computation, and Bayesian kernel machine regression (BKMR) models were utilized to explore the associations between urinary phthalate metabolites and accelerated aging. Three groups of physical activity with different intensities were used to evaluate the modifying effects on the above associations. Results indicated that most phthalate metabolites were significantly associated with BioAgeAccel and PhenoAgeAccel, with effect values (ß) ranging from 0.16 to 0.21 and 0.16-0.37, respectively. The WQS indices were positively associated with BioAgeAccel (0.33, 95% CI: 0.11, 0.54) and PhenoAgeAccel (0.50, 95% CI: 0.19, 0.82). Quantile g-computation indicated that phthalate mixtures were associated with accelerated aging, with effect values of 0.15 (95% CI: 0.02, 0.28) for BioAgeAccel and 0.39 (95% CI: 0.12, 0.67) for PhenoAgeAccel respectively. The BKMR models indicated a significant positive association between the concentrations of urinary phthalate mixtures with the two indicators. In addition, we found that most phthalate metabolites showed the strongest effects on accelerated aging in the no physical activity group and that the effects decreased gradually with increasing levels of physical activity (P < 0.05 for trend). Similar results were also observed in the mixed exposure models (WQS and Quantile g-computation). This study indicates that phthalates exposure is associated with accelerated aging, while physical activity may be a crucial barrier against phthalates exposure-related aging.

Temporal trends in the prevalence and death of ischemic heart disease in women of childbearing age from 1990 to 2019: a multilevel analysis based on the Global Burden of Disease Study 2019.

Background: Our objective is to describe the current prevalence and death of ischemic heart disease (IHD) in women of childbearing age (WCBA) at the global, regional, and national levels and to analyze its temporal trends from 1990 to 2019. Methods: WCBA was defined as women aged 15-49 years. Estimates and 95% Uncertainty Intervals (UI) of IHD prevalence and death numbers for seven age groups were extracted from the 2019 Global Burden of Disease Study. The age-standardized prevalence and death rate (ASPR and ASDR) of IHD in WCBA was estimated using the direct age-standardization method. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) to represent the temporal trends from 1990 to 2019. Results: Between 1990 and 2019, the global ASPR of IHD experienced a 3.21% increase, culminating in 367.21 (95% UI, 295.74-430.16) cases per 100,000 individuals. Conversely, the ASDR decreased to 11.11 (95% UI, 10.10-12.30) per 100,000 individuals. In 2019, among the five sociodemographic index (SDI) regions, the highest ASPR was observed in the high-middle SDI region, whereas the highest ASDR was found in the low-middle SDI region. Regionally, the Caribbean reported the highest ASPR (563.11 per 100,000 individuals; 95% UI, 493.13-643.03), and Oceania reported the highest ASDR (20.20 per 100,000 individuals; 95% UI, 13.01-31.03). At the national level, Trinidad and Tobago exhibited the highest ASPR (730.15 per 100,000 individuals; 95% UI, 633.96-840.13), and the Solomon Islands had the highest ASDR (77.77 per 100,000 individuals; 95% UI, 47.80-121.19). Importantly, over the past three decades, the global ASPR has seen a significant increase [AAPC = 0.11%, 95% Confidence Interval (CI): 0.09-0.13; P < 0.001], while the ASDR has demonstrated a significant decreasing trend (AAPC = -0.86%, 95% CI: -1.11 to -0.61; P < 0.001). Air pollution, tobacco use, high systolic blood pressure, elevated body mass index, dietary risks, and high LDL cholesterol have been identified as the leading six risk factors for IHD-related deaths among WCBA in 2019. Conclusions: Despite the significant decline in the global ASDR for IHD among WCBA over the last thirty years, the ASPR continues to escalate. We need to remain vigilant about the increased burden of IHD in WCBA. It calls for aggressive prevention strategies, rigorous control of risk factors, and the enhancement of healthcare coverage to mitigate the disease burden of IHD among WCBA in forthcoming years.

Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

The Association of Preoperative Diabetes With Postoperative Delirium in Older Patients Undergoing Major Orthopedic Surgery: A Prospective Matched Cohort Study.

BACKGROUND: Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD. METHODS: This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1-7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power. RESULTS: A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4-8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6-60%; P = .021) of the association between diabetes and POD. CONCLUSIONS: This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.

Contribution of intraoperative electroencephalogram suppression to frailty-associated postoperative delirium: mediation analysis of a prospective surgical cohort.

BACKGROUND: Frailty is a risk factor for postoperative delirium (POD), and has led to preoperative interventions that have reduced, but not eliminated, the risk. We hypothesised that EEG suppression, another risk factor for POD, mediates some of the frailty risk for POD. METHODS: A prospective cohort study enrolled patients aged 65 yr or older, scheduled for noncardiac surgery under total intravenous anaesthesia. Frailty was assessed using the FRAIL scale. Cumulative duration of EEG suppression, defined as an amplitude between -5 and 5 µV for >0.5 s during anaesthesia, was measured. POD was diagnosed by either confusion assessment method (CAM), CAM-ICU, or medical records. The severity of POD was assessed using the Delirium Rating Scale - Revised-98 (DRS). Mediation analysis was used to estimate the relationships between frailty, EEG suppression, and severity of POD. RESULTS: Among 252 enrolled patients, 51 were robust, 129 were prefrail, and 72 were frail. Patients classified as frail had higher duration of EEG suppression than either the robust (19 vs 0.57 s, P<0.001) or prefrail groups (19 vs 3.22 s, P<0.001). Peak delirium score was higher in the frail group than either the robust (17 vs 15, P<0.001) or prefrail groups (17 vs 16, P=0.007). EEG suppression time mediated 24.2% of the frailty-DRS scores association. CONCLUSION: EEG suppression time mediated a statistically significant portion of the frailty-POD association in older noncardiac surgery patients. Trials directed at reducing EEG suppression time could result in intraoperative interventions to reduce POD in frail patients. CLINICAL TRIAL REGISTRATION: ChiCTR2000041092 (Chinese Clinical Trial Registry).

Prevalence and factors associated with late diagnosis among older adults living with HIV in liuzhou, China: 2010-2020.

This paper aimed to quantify and characterize the prevalence and associated factors for late diagnosis in older adults living with human immunodeficiency virus (HIV) in Liuzhou, China, from 2010 to 2020. The characteristics of older adults living with HIV were described separately in time, space and population. Multivariate logistic regression analysis evaluates the factors influencing late diagnosis in HIV-positive adults ≥ 50 years of age. The majority of older adults living with HIV were over 60 years old, male, and with CD4 counts < 200 cells/µl at diagnosis, with most late diagnoses being more likely to report heterosexual transmission. These two factors may potentially provide a positive influence on late diagnosis: older and CD4 counts < 500 cells/µl. In contrast, females and those with homosexual or other transmission provide a negative. These results suggest that late diagnosis of HIV-positive adults ≥ 50 years of age remains a severe and growing epidemiological issue.

The effect of protease inhibitors-based antiretroviral therapy on serum/plasma interleukin-6 levels among PLHIV: a systematic review and meta-analysis.

Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside reverse-transcriptase inhibitors (2NRTIs), which enable to achieve and maintain viral suppression, restore, and preserve immune function. However, there were inconsistent findings on the levels of interleukin-6 (IL-6) levels. Systematic review and meta-analysis were performed to quantify the pooled effects of PIs/r-based antiretroviral therapy (ART) on serum/plasma IL-6 levels in people living with the HIV (PLHIV). PubMed, Web of Science, and Embase were searched from the earliest record to November 4, 2020. Data analysis was conducted on Stata version 16 and Review Manager 5.3. A random-effect model was used to compute a pooled effect size and weighted mean difference (WMD) was considered the summary effect size. Heterogeneity between studies was estimated by Cochrane's Q test (χ2 test) and I2 statistic and subgroup analysis were performed to explore the source of heterogeneity. Initial search identified 3098 records and 5 studies (7 trials) met inclusion criteria. The pooled mean difference in serum/plasma IL-6 levels from baseline to follow-up was 0.534 pg/ml (95% confidence interval: -0.012, 1.08, P = 0.05, I2 = 76.4%). In subgroup analysis, there was a significant association between increased serum/plasma IL-6 levels and age group ≥ 35 years old, baseline CD4+ counts < 350 cell/mm3 , and mean viral load ≥ 4.5 log10 copies/ml. We found that serum/plasma IL-6 levels increased after combined ART among treatment-naïve individuals who initiated a successful combination of PIs/r with 2NRTIs. This result also highlights the need to monitor serum/plasma IL-6 levels during antiviral therapy, which may aid in the effective future treatment of systemic inflammation and related disorders following elevated IL-6 levels.

Involvement of N6-methyladenosine modifications of long noncoding RNAs in systemic lupus erythematosus.

BACKGROUND: LncRNAs are potential biomarkers for SLE, but the epigenetic regulatory mechanisms of N6-methyladenosine (m6A) modification in SLE remain largely unclear. METHODS: In this study, we established m6A modification profile and investigated the potential roles of m6A-related lncRNAs in SLE. The m6A modification profile of SLE was established using MeRIP-seq. Four potential m6A related-lncRNAs (linc02446, linc01410, Xist, and PSMB8-AS1) were selected for validation using qRT-PCR, and their expression and association with clinical characteristics with SLE were evaluated. RESULTS: Overall, m6A level was lower in patients with SLE than in controls. Compared with controls, the expression of the two m6A related-lncRNAs (Xist and PSMB8-AS1) was downregulated in patients with SLE (all P < 0.05); the linc02446 was up-regulated in PBMCs of patients with SLE (Z=-2.738, P = 0.006), while it was not differentially expressed in T cells (Z=-0.387, P = 0.699). No significant alteration in linc01410 expression was observed in patients (Z=-0.940, P = 0.347). The lower expression levels of Xist and PSMB8-AS1 were associated with many clinical manifestations in patients with SLE (all P < 0.05). Additionally, mRNAs co-expressed with m6A related-lncRNAs (Xist, linc02446, and PSMB8-AS1) also participated in SLE. CONCLUSION: These results suggest that m6A methylation and m6A related-lncRNAs might be involved in the pathogenesis of SLE. Thus, our findings provide some clues on the potential function of lncRNAs that m6A modification may target in novel therapeutic or diagnostic strategies for SLE.

The Effect of Rosuvastatin on Plasma/Serum Levels of High-Sensitivity C-Reactive Protein, Interleukin-6, and D-Dimer in People Living with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

Rosuvastatin therapy might have an effect on the inflammatory and coagulation biomarkers. However, the evidence about the effect of rosuvastatin therapy on the high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer levels among people living with human immunodeficiency virus (PLHIV) is still unclear. Therefore, this study investigated the relational effect of rosuvastatin therapy on serum/plasma hsCRP, IL-6 and D-dimer levels in PLHIV. The literature search was done from Embase, PubMed, and Web of Science databases. The review and meta-analysis included studies written in English language up to January 4, 2020. Random effects model was used to evaluate the pooled standard mean difference with 95% confidence interval. A meta-analysis was performed using nine articles with 392 PLHIV. The result revealed that the plasma/serum levels of IL-6 were significantly reduced after the intervention. However, hsCRP and D-dimer levels showed no significant difference (p > .05) between before and after the intervention. The subgroup analysis showed that there was significant association between PLHIV ages <45 years and cohort studies with IL-6 levels. The current CD4+ counts ≥350 cells/mm3 correlated with hsCRP as well as IL-6. Similarly, nadir CD4+ counts ≥200 cells/mm3 and duration of HIV diagnosis <10 years also showed significant association with IL-6 and D-dimer levels. It was also indicated that participants who were under antiretroviral drug for <7 years were significantly associated with hsCRP levels. This study established that IL-6 levels were significantly reduced after the intervention while hsCRP and D-dimer levels showed no significant difference between before and after the intervention.

HIV Prevalence and Factors Influencing the Uptake of Voluntary HIV Counseling and Testing among Older Clients of Female Sex Workers in Liuzhou and Fuyang Cities, China, 2016-2017: A Cross-Sectional Study.

OBJECTIVE: To compare the prevalence of HIV and associated factors for participating HIV voluntary counseling and testing (VCT) among older clients of female sex workers (CFSWs) in Liuzhou City and Fuyang City in China. METHODS: A cross-sectional study was conducted and the study employed 978 male CFSWs, aged 50 years and above from October 2016 to December 2017. All participants were required to complete a questionnaire and provide blood samples for HIV testing. Multivariate logistic regression analysis was used to analyze the influential factors of using VCT program and tested for HIV. RESULTS: The HIV infection prevalence rate was 1.2% and 0.5%, while 52.3% and 54.6% participants had ever utilized VCT service and tested for HIV in Liuzhou City and Fuyang City, respectively. The older CFSWs who ever heard of VCT program were more likely to uptake VCT program in both cities (ORLiuzhou = 2.224, ORFuyang = 2.421). Participants, whose marital status was married or cohabiting (ORLiuzhou = 0.548, ORFuyang = 0.495), who have stigma against individuals who are living with HIV/AIDS (ORLiuzhou = 0.273, ORFuyang = 0.371), whose monthly income is more than 500 yuan (ORLiuzhou = 0.622, ORFuyang = 0.600), and whose age is more than 60 years old (ORLiuzhou = 0.639, ORFuyang = 0.554), were less likely to visit VCT clinics. Those who are worried about HIV-infected participants were more likely to utilize VCT services in Fuyang City (AOR = 1.838, 95%CI : 1.146-2.948). CONCLUSION: Combine strategy will be needed to promote the utilization of VCT service, based on the socioeconomic characteristics of older male CFSWs in different cities of China.

Association of omentin-1, adiponectin, and resistin genetic polymorphisms with systemic lupus erythematosus in a Chinese population.

OBJECTIVE: An increasing number of studies have demonstrated the roles of adipokines in systemic lupus erythematosus (SLE). We aimed to investigate the association of genetic variations of omentin-1, adiponectin, and resistin with SLE susceptibility. METHODS: We selected 623 SLE patients and 665 normal controls in the present study. Genotyping of omentin-1 rs2274907, rs35779394, rs79209815, and rs13376023; adiponectin rs16861194 and rs266729; and resistin rs1862513, rs3745368, and rs3745367 was conducted by TaqMan SNP genotyping assays. RESULTS: Overall, we found no significant differences in the allele or genotype frequencies of the nine studied SNPs between the SLE patients and controls. However, an increased frequency of the resistin rs3745368 variant was observed in the SLE patients under the dominant model (P = 0.024). In omentin-1, the rs13376023 A allele was found to be related to oral ulcers in SLE patients (P = 0.013), and the rs35779394 C and rs13376023 A allele frequencies were significantly lower in SLE patients with BMI ≥ 24 kg/m2 (P = 0.019, P = 0.033, respectively). For resistin, the frequencies of the rs3745368 AA genotype and A allele were lower in SLE patients with discoid rash (P = 0.036, P = 0.011), and the rs3745368 A allele frequency was higher in SLE patients with lupus nephritis (P = 0.018). The resistin rs3745367 AA genotype and A allele frequencies were related to the occurrence of renal disorder in SLE patients (P = 0.024, P = 0.009). The haplotype analysis showed that the CGA haplotype of resistin was associated with susceptibility to SLE (P = 0.005). No significant associations of plasma omentin-1, adiponectin or resistin levels with their respective genotypes were found in SLE patients. CONCLUSIONS: In summary, omentin-1, adiponectin and resistin SNPs are not associated with the genetic background of SLE in Chinese patients. However, omentin-1 and resistin genetic variations might contribute to several clinical phenotypes of SLE.

Potential link between m6A modification and systemic lupus erythematosus.

The field of m6A modification and epitranscriptomics has recently attracted much attention. More methods allowing for precise m6A site profiling and location are developed and crucial players of m6A modification machinery are increasingly identified. Although some challenges remain, m6A modification is found to modulate almost all aspects of RNA metabolism, such as splicing, stability, structure, translation, and export. Thus, m6A modification adds a new layer of post-transcriptional gene expression regulation, and it is implicated in T cell response to HIV infection, type I interferon production, and T cell differentiation and homeostasis. Moreover, evidence supporting its involvement in various human diseases including cancers is accumulating. Given the role of m6A modification in gene expression regulation and immune response, it invites the speculation that m6A modification may justify the pathogenesis of systemic lupus erythematosus (SLE) and take part in the initiation and progression of SLE. In this review, we introduce the widespread existence of m6A modification and briefly discuss components of m6A modification machinery in mammals. We mainly summarize the studies reporting the mechanisms of m6A modification in gene expression regulation through modulating pre-mRNA splicing, mRNA stability, RNA structure, translation, and pri-miRNA processing. Biological functions related to immune response of m6A modification and the implication of m6A modification in cancers are highlighted. In the end, we surmise the potential link between m6A modification and SLE.

Intratumoral and peritumoral expression of CD68 and CD206 in hepatocellular carcinoma and their prognostic value.

The aims of the present study were to determine whether the changes in density and location of CD68-positive and CD206-positive macrophages contribute to progression of hepatocellular carcinoma (HCC) and to evaluate prognostic values of these cells in post-surgical patients. A retrospective study involving 268 HCC patients was conducted. CD68-positive and CD206-positive macrophage infiltration in HCC tissues and adjacent tissues was examined by immunohistochemistry (IHC) and the relationship between the clinicopathological features and prognosis was analyzed. Receiver operating characteristics (ROC) curve was used to calculate diagnostic accuracy. There was an increase in CD68-positive and CD206-positive macrophage infiltration in adjacent tumor tissues compared with tumor tissues. ROC curve identified their optimal diagnostic cut-off values. The survival analysis showed that increased CD68 expression in adjacent tissues conferred superior overall survival (OS) and disease-free survival (DFS), while increase of CD206 in tumor yielded inferior OS and DFS. Cox regression analysis suggested both CD68-positive macrophages in adjacent area and intratumor CD206-positive macrophages as independent prognostic biomarkers for post-surgical HCC patients. Finally, a combination of CD68/CD206 and HBV-positive further improved prognostic stratification, especially in DFS. These results provide the first evidence for region- and subset-dependent involvement of CD68 and CD206 cells in HCC progression. A combination of CD68/CD206 density and HBV-positivity improves further predictive value for post-operative recurrence of HCC. Quantification of CD68/CD206 macrophages and their distribution can be exploited for better postsurgical management of HCC patients. These findings provide a basis for developing novel treatment strategies aimed at re-educating macrophages in tumor microenvironment.

Competitive endogenous RNA network: potential implication for systemic lupus erythematosus.

INTRODUCTION: Competitive endogenous RNA (ceRNA) hypothesis proposes that RNA transcripts, both coding and non-coding, crosstalk with and coregulate each other using microRNA response elements (MREs). CeRNA analysis tremendously expands functional information of coding and non-coding RNAs. Mounting evidence have shown that various types of RNAs, including pseudogenes, long non-coding RNAs, circular RNAs, and messenger RNAs, can function as ceRNAs in distinct physiological and pathophysiological states. Many validated ceRNA pairs participate in the initiation and progression of cancers, and systemic ceRNA network analyses revealing potential of ceRNAs in diagnosis, therapy, and prognosis of cancers have also been performed. Areas covered: This review concisely introduces ceRNA hypothesis and characteristics of ceRNA regulations. The major sections focus on representative examples of both protein coding and non-coding RNA transcripts acting as ceRNAs. CeRNA prediction programs and databases and implications of ceRNA network in cancers are then discussed. In the end, we surmise potential implications of ceRNA network for SLE. Expert opinion: The role of ceRNA network in systemic lupus erythematosus (SLE) remains undefined. We speculate that dissecting ceRNA network in SLE may help expand our comprehension of roles of transcriptome, particularly non-coding transcripts, and richen our knowledge of pathogenesis, diagnosis, and therapy of SLE.

MicroRNA-210 and its theranostic potential.

INTRODUCTION: MicroRNAs (miRNAs) are a set of small single-stranded noncoding RNAs with diverse biological functions. As a prototypical hypoxamir, human microRNA-210 (hsa-miR-210) is one of the most widely studied miRNAs thus far. In addition to its involvement in sophisticated regulation of numerous biological processes, miR-210 has also been shown to be associated with the development of different human diseases including various types of cancers, cardiovascular and cerebrovascular diseases, and immunological diseases. Given its multi-faceted functions, miR-210 may serve as a novel and promising theranostic target for prevention and treatment of diseases. Areas covered: This review aims to provide a comprehensive overview of miR-210, the regulation of its expression, biological functions and molecular mechanisms, with particular emphasis on its diagnostic and therapeutic potential. Expert opinion: Although the exact roles of miR-210 in various diseases have not been fully clarified, targeting miR-210 may be a promising therapeutic strategy. Further investigations are also needed to facilitate therapeutic-clinical applications of miR-210 in human diseases.

Prevalence and factors associated with late HIV diagnosis.

While highly active antiretroviral therapy has been successful in delaying progression into AIDS, late HIV diagnosis remains a major contributor to the mortality and morbidity of AIDS. An epidemiological study was conducted to evaluate the prevalence and factors of late diagnosis and the characteristics of those individuals with late diagnosis in Liuzhou city. Patients with late diagnosis were defined as either those who were diagnosed with AIDS at the time of HIV diagnosis or as those who developed AIDS no more than 1 year after HIV diagnosis. Of 899 participants, 72.6% had a late diagnosis. Common characteristics of those who experienced late diagnosis included older participants, those who were unexpectedly diagnosed while seeking other medical attention, participants who believed they could not acquire HIV from their regular heterosexual partners, those who never considered getting tested for HIV, and patients with unexplained weight loss, angular cheilitis, or prolonged fever prior to HIV diagnosis. On the other hand, those participants who were diagnosed via testing at compulsory rehabilitation centers and those whose annual household income was greater than 30,000 Yuan were less likely to be diagnosed late. These results suggested that late HIV diagnosis is common in Liuzhou city, and it is essential to promote appropriate strategies to detect HIV infections earlier. Strategies that require HIV/AIDS patients to notify their spouse/sexual-partners about their HIV-positive results within one month and start provider-initiated HIV testing and counseling in medical facilities are beneficial to earlier HIV diagnosis.

Peripheral blood lymphocyte/monocyte ratio predicts outcome for patients with diffuse large B cell lymphoma after standard first-line regimens.

To determine whether peripheral blood absolute lymphocyte/absolute monocyte counts ratio (ALC/AMC ratio) at diagnosis predicts survival of diffuse large B cell lymphoma (DLBCL) patients treated with standard first-line regimens, we retrospectively analyzed 244 patients with DLBCL who were treated with standard cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, or rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone. Progression-free survival and overall survival (PFS and OS) were estimated using the Kaplan-Meier method and two-tailed log-rank; The Cox proportional hazards model was used to evaluate ALC/AMC ratio as prognostic factors when adjusting for the International Prognostic Index (IPI). On univariate and multivariate analyses performed with factors included in the IPI, the ALC/AMC ratio at diagnosis remained an independent predictor of OS and PFS (OS: P < 0.001; PFS: P < 0.001). Patients with lower ALC/AMC ratio (<3.8) seemed to have lower complete remission rate, 2-year PFS and 3-year OS when compared to patients with ALC/AMC ratio ≥3.8, respectively (26 versus 90 %, P < 0.001; 18 versus 82 %, P < 0.001; 24 versus 86 %; P < 0.001, respectively). Moreover, the ALC/AMC ratio was able to further risk-stratify IPI 0-2 and three-five risk patient groups, respectively. The ALC/AMC ratio at the time of diagnosis may provide additional prognostic information beyond that of the IPI for patients with DLBCL who receive standard first-line regimens.

Association of IFIH1 rs1990760 polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

Published data on the association between the IFIH1 rs1990760 polymorphism and multiple autoimmune diseases are controversial and inconclusive. To more precisely estimate the association between the IFIH1 rs1990760 polymorphism and susceptibility to autoimmune diseases, a meta-analysis was conducted. Studies examining the association of the IFIH1 rs1990760 polymorphism with autoimmune diseases were exhaustively searched using PubMed, Web of Science and a review of the references. A total of 19 studies with 26 comparisons including 8 type 1 diabetes (T1D), 5 systemic lupus erythematosus (SLE), 5 Graves' disease (GD), 2 multiple sclerosis (MS), 2 rheumatoid arthritis (RA), 2 Hashimoto's thyroiditis (HT), 2 autoimmune Addison's disease (AAD) were available for this meta-analysis. Meta-analysis was performed for genotype T/T + T/C (dominant model), genotype T/T (recessive model) and T-allele in fixed or random-effects models. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for T-allele were T1D (OR = 1.184, 95% CI = 1.142-1.229), SLE (OR = 1.143, 95% CI = 1.073-1.217), MS (OR = 1.181, 95% CI = 1.062-1.313) and RA (OR = 1.115, 95% CI = 1.004-1.239), respectively. For T1D and SLE, significant association was observed in the population of European ancestry, but not in the Asian population. This meta-analysis demonstrates that the IFIH1 rs1990760 T-allele confers susceptibility to T1D, SLE, MS and RA and suggests that the IFIH1 rs1990760 polymorphism might have no effect on GD and AAD. Our result provides further evidence for the notion of common gene underlying multiple autoimmune diseases.

The dual nature of Ets-1: focus to the pathogenesis of systemic lupus erythematosus.

E26 transformation-specific-1 (Ets-1) belongs to the Ets family of transcription factors which share a common 85-amino-acid DNA-binding domain. Ets-1 is essential to regulation of the immune system including immune cell proliferation and differentiation. Past data demonstrated Ets-1 play a role in negative regulation of Th17 cells and B cells differentiation. Recently, association of genetic variation in Ets-1 with susceptibility to systemic lupus erythematosus (SLE) have been independently identified by two Genome-wide association studies (GWAS), and decreased Ets-1mRNA level in peripheral blood mononuclear cells (PBMCs) of SLE patients has been reported. All these findings suggest that the transcription factor is broadly linked to the pathogenesis of this disease. However, aberrant control of other immune cells and effector molecules illuminated the complexities of Ets-1 biology. In this review article, we will focus on the dual nature of Ets-1 and discuss its regulatory capability. Hopefully the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for SLE.