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).

HIV associated factors among men who have sex with men in Maanshan, China: a cross-sectional study.

BACKGROUND: This study conducted a survey of men who have sex with men (MSM) in Maanshan City of Anhui Province to assess the risk behaviors related to human immunodeficiency virus (HIV) infection. METHODS: A cross-sectional survey was conducted from June 2016 to June 2019. The MSM were recruited by a peer-driven sampling method. A face-to-face interview with anonymous questionnaire was used for data collection. The information collected by the survey was summarized and epidemiology described the basic characteristics of MSM, and then the related factors were statistically analyzed. RESULTS: A total of 934 MSM were recruited with a average age was 30.5 (SD = 8.90) years old, including 816 (87.4%) HIV negative participants and 118 (12.6%) HIV positive ones. This study showed that freelancer (OR = 4.02, 95% CI: 1.96-8.23), scope of sexual partners distribution (OR = 1.78, 95% CI: 1.36-2.33), number of male sexual partners (OR = 2.11, 95% CI: 1.47-3.02), role of anal sex with men was receptive (OR = 2.54, 95% CI: 1.25-5.13) and versatile (OR = 2.34, 95% CI: 1.31-4.19) and non-steady sex partners (OR = 2.14, 95% CI: 1.56-2.93) were risk factors for HIV infection, while monthly income (OR = 0.68, 95% CI: 0.57-0.82), education level (OR = 0.79, 95% CI: 0.66-0.95), frequency of condom use (OR = 0.53, 95% CI: 0.35-0.81) and number of oral sex partners (OR = 0.35, 95% CI: 0.24-0.51) in the past 6 months were protective factors for HIV infection. CONCLUSION: Risk behaviors were common in MSM, and urgent need for targeted and comprehensive interventions to reduce risky sexual behaviour and to prevent HIV infection in MSM.

Global Chronic obstructive pulmonary disease burden attributable to air pollution from 1990 to 2019.

BACKGROUND: The disease burden attributable to chronic obstructive pulmonary disease (COPD) is significant worldwide. Some studies have linked exposure to air pollution to COPD, but there has been little research on this. METHODS: We aimed to assess the COPD-related disease burden attributable to air pollution from multiple epidemiological perspectives. This study conducted a three-stage analysis. Firstly, we reported on the burden of disease worldwide in 2019 by different subgroups including sex, age, region, and country. Secondly, we studied the trends in disease burden from 1990 to 2019. Finally, we explored the association of some national indicators with disease burden to look for risk factors. RESULTS: In 2019, the death number of COPD associated with air pollution accounted for 2.32% of the total global death, and the number of DALY accounted for 1.12% of the global DALY. From 1990 to 2019, the death number of COPD associated with air pollution increased peaked at 1.41 million in 1993, fluctuated, and then declined. We found the same temporal pattern of DALY. The corresponding age-standardized rates had been falling. At the same time, the burden of COPD associated with air pollution was also affected by some national indicators. CONCLUSIONS: This study indicated that air pollution-related COPD contributed to a significant global disease burden. We called for health policymakers to take action and interventions targeting vulnerable countries and susceptible populations.

Proton pump inhibitors induce changes in the gut microbiome composition of systemic lupus erythematosus patients.

BACKGROUND: Currently, few studies focus on the association between gut microbiota and systemic lupus erythematosus (SLE), and much less studies consider the effect of drug usage. Proton pump inhibitors (PPIs) are commonly used to treat drug-related gastrointestinal damage in SLE patients. Therefore, the purpose of this study is to examine the gut microbiota of SLE patients using PPIs. METHODS: Fecal samples from 20 SLE patients with PPIs (P-SLE), 20 SLE patients without PPIs (NP-SLE) and 17 healthy controls (HCs) were obtained. The structure of the bacterial community in the fecal samples was analyzed by 16S rRNA gene sequencing. Redundancy analysis (RDA) was performed to observe the relationship between clinical variables and microbiome composition in P-SLE and NP-SLE patients. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, functional capabilities of microbiota were estimated. Network analysis was performed to analyze the association of metabolic pathway alterations with altered gut microbiota in P-SLE and NP-SLE patients. RESULTS: P-SLE patients exhibited increased alpha-diversity and an altered composition of the gut microbiota compared with NP-SLE patients. The alpha-diversity of NP-SLE patients was significantly lower than HCs but also of P-SLE patients, whose alpha-diversity had become similar to HCs. Compared with NP-SLE patients, the relative abundances of Lactobacillus, Roseburia, Oxalobacter, and Desulfovibrio were increased, while those of Veillonella, Escherichia, Morganella, Pseudomonas and Stenotrophomonas were decreased in P-SLE patients. RDA indicated that PPI use was the only significant exploratory variable for the microbiome composition when comparing SLE patients. KEGG analysis showed that 16 metabolic pathways were significantly different between NP-SLE and P-SLE patients. These metabolic pathways were mainly associated with changes in Escherichia, Roseburia, Stenotrophomonas, Morganella and Alipipes as determined by the network analysis. CONCLUSIONS: PPI use is associated with an improved microbiome composition of SLE patients as it 1) increases alpha-diversity levels back to normal, 2) increases the abundance of various (beneficial) commensals, and 3) decreases the abundance of certain opportunistic pathogenic genera such as Escherichia. Validation studies with higher patient numbers are however recommended to explore these patterns in more detail.

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.

Identification of new susceptibility loci associated with rheumatoid arthritis.

OBJECTIVES: The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA). METHODS: We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function. RESULTS: We identified five new susceptibility loci (IL12RB2, BOLL-PLCL1, CCR2, TCF7 and IQGAP1; pmeta <5.00E-08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in IQGAP1 have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in TCF7 was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets. CONCLUSION: This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.

Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis.

OBJECTIVE: Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis. METHODS: Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies. RESULTS: A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A. CONCLUSION: The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.

Circular RNA expression profile and potential function of hsa_circ_0045272 in systemic lupus erythematosus.

Circular RNAs (circRNAs) represent a class of non-coding RNAs that form covalently closed RNA circles with extensive expression and conservation in mammals. Circular RNAs regulate gene expression through acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Accumulating evidence supports the implication of circRNAs in a variety of human diseases, but studies of circRNA role in systemic lupus erythematosus (SLE) are lacking. The present study measured the circRNA expression profiles in T cells from patients with SLE and healthy controls with human circRNA microarray and identified 127 differentially expressed circRNAs in SLE patients. Down-regulation of hsa_circ_0045272 in SLE T cells was verified with quantitative PCR. Jurkat cells with stable hsa_circ_0045272 knockdown were generated using specific lentiviral short hairpin RNA for functional studies. Flow cytometric analysis indicated that hsa_circ_0045272 knockdown significantly up-regulated the early apoptosis of Jurkat cells. Meanwhile, ELISA showed that hsa_circ_0045272 knockdown significantly enhanced interleukin-2 production of activated Jurkat cells. Then, ceRNAs were predicted for hsa_circ_0045272 and the significant down-regulation of two mRNAs predicted as ceRNAs, NM_003466 (PAX8) and NM_015177 (DTX4), but not their corresponding proteins, was validated. Furthermore, dual luciferase reporter assay indicated binding of hsa_circ_0045272 with hsa-miR-6127. Circular RNA-mRNA co-expression networks showed the correlation of circRNAs with mRNAs and provided additional clues to circRNA functions. Our study demonstrated dysregulated circRNAs in SLE and revealed the function of hsa_circ_0045272 in negatively regulating apoptosis and interleukin-2 secretion and its potential mechanism. The implication of hsa_circ_0045272 and other abnormal circRNAs in SLE merits further investigation.

The expression levels of long noncoding RNAs lnc0640 and lnc5150 and its gene single-nucleotide polymorphisms in rheumatoid arthritis patients.

OBJECTIVES: The aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single-nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients. METHODS: The expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real-time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP-genotyping assays in 627 RA patients and 590 controls. RESULTS: The lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P < 0.001) compared to controls. There were significant associations of lnc0640 and lnc5150 levels with C-reactive protein in RA patients (P = 0.011 and P = 0.014, respectively), while lnc5150 level was associated with erythrocyte sedimentation rate (P = 0.022). TT genotype of rs13039216 in lnc0640 gene was statistically associated with a reduced risk of RA (TT vs CC; P = 0.046), and a decreased risk of rs13039216 variant was observed under the recessive model (P = 0.038). In addition, the G allele of rs141561256 polymorphism in lnc5150 gene was significantly associated with rheumatoid factor in RA patients (P = 0.034). There were no associations between lnc0640 and lnc5150 levels and their respective genotype in RA patients. CONCLUSIONS: The expressions of lnc0640 and lnc5150 were alternated in the RA patients, suggesting that these lncRNAs may involve in the development of RA.

Translation of noncoding RNAs: Focus on lncRNAs, pri-miRNAs, and circRNAs.

Mammalian genome is pervasively transcribed, producing large number of noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), primary miRNAs (pri-miRNA), and circular RNAs (circRNAs). The translation of these ncRNAs has long been overlooked. Increasing studies, however, based on ribosome profiling in various organisms provide important clues to unanticipated translation potential of lncRNAs. Moreover, a few functional peptides encoded by lncRNAs and pri-miRNAs underline the significance of their translation. Recently, several novel researches also evidence the translation of endogenous circRNAs. Given the functional significance exemplified by peptides translated by some ncRNAs and their pervasive translation, it is not too far-fetched to image that abnormal translation of ncRNAs may contribute to human diseases. Through challenging, deciphering ncRNA translation is required for comprehensive understanding of biology and medicine. In this review, we firstly present evidence concerning translation potential of lncRNAs and go on to introduce a few functional short peptides encoded by lncRNAs. Then, salient observations showing translation of pri-miRNAs and circRNAs are described in detail. We end by discussing the impact of ncRNA translation beyond producing peptides and referring briefly to the potential role of abnormal ncRNA translation in human diseases.

Comprehensive long non-coding RNA expression profiling reveals their potential roles in systemic lupus erythematosus.

Long non-coding RNAs can regulate gene transcription, modulate protein function, and act as competing endogenous RNA. Yet, their roles in systemic lupus erythematosus remain to be elucidated. We determined the expression profiles of lncRNAs in T cells of SLE patients and healthy controls using microarrays. Up to 1935 lncRNAs and 1977 mRNAs were differentially expressed. QRT-PCR showed downregulated uc001ykl.1 and ENST00000448942 in SLE patients. Expression of uc001ykl.1 correlated with erythrocyte sedimentation rate (ESR) and C-reactive protein, whereas ENST00000448942 level correlated with ESR and anti-Sm antibodies. Short time-series expression miner analysis revealed some lncRNAs whose expressions might correlate with disease activity of SLE patients. Coding-non-coding gene coexpression analyses showed differential lncRNAs might operate via modulating expressions of their correlated, relevant mRNAs in SLE. Differential lncRNAs might also function through their ceRNAs. Our study established that the aberrant expression profiles of lncRNAs may play a role in SLE and thus warrant further investigation.

HIV transmission and related risk factors among serodiscordant couples in Liuzhou, China.

To evaluate the incidence and risk factors for human immunodeficiency virus (HIV) seroconversion of HIV-negative partners among HIV-discordant couples in Liuzhou, China, 1854 eligible HIV-serodiscordant couples were retrospectively identified through the HIV epidemiology and follow-up database from January 1, 1996 to June 30, 2013. Cox proportional-hazards model was used to examine risk factors related to HIV seroconversion of negative partners. Finally, 125 HIV seroconversion occurred over 4963.5 person-years, resulting in an overall HIV incidence of 2.52/100 person-years. HIV-positive partners with the last CD4 counts of 350 cells/ul or more were significantly protected against HIV seroconversion compared with those CD4 counts of less than 200 cells/ul (aHR = 0.46, 95% CI: 0.27-0.81, P < 0.01). Men with HIV-positive wives (aHR: 1.96, 95% CI: 1.27-3.02, P < 0.01), HIV-positive partners who did not receive ART before their HIV-negative partners' seroconversion (aHR: 2.22, 95% CI, 1.41-3.51, P < 0.01) and patients reported intermittent condom use (aHR: 7.60, 95% CI, 4.37-13.21, P < 0.01) were associated with increased risk of HIV seroconversion. HIV-negative partners remain high risk of HIV infection in Liuzhou city. Comprehensive package of HIV prevention services should contribute to reduction in HIV transmission of discordant couples.

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.

HIV/AIDS stigma among older PLWHA in south rural China.

Stigma is a common problem among people living with HIV/AIDS (PLWHA). However, little is known about HIV/AIDS-related stigma in older PLWHA over the age of 50. This study described the stigma of HIV/AIDS and its factors based on 120 PLWHA aged 50 or older in an area of high HIV prevalence in south rural China. Each participant completed a face-to-face questionnaire that collected information on demographic characteristics, AIDS-related events and experience of HIV/AIDS-related stigma. Finally, only 18.1% reported experiencing external stigma compared with 64.3% feeling internal stigma. Regression analysis indicated that social support and health status were the two variables that were significantly predictive of both external and internal stigma. Whatever, the more support were received from family members by PLWHA, the less external stigma was perceived. Negative marital situation was also related to external stigma. Reducing HIV/AIDS stigma requires a supportive environment, positive attitude and correct knowledge of AIDS. Health workers and policy makers should take practical approaches to reduce prejudice.

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.

Prevalence of systemic lupus erythematosus and risk factors in rural areas of Anhui Province.

Systemic lupus erythematosus (SLE) is a severe complex rheumatic disease, but good estimate of its prevalence and risk factors is lacking in China. The aim of the study was to explore the prevalence of SLE and risk factors in rural areas of Anhui Province of China. Eleven counties were randomly selected in Anhui Province, and then, 15% of the villages in selected counties were randomly sampled as study sites. Patients with SLE were identified through two phases. Based on the cases identified, a population-based case-control study was designed to examine risk factors associated with SLE. A total of 1,253,832 individuals and identified 471 SLE cases were surveyed. Crude and age-standardized prevalence were estimated at 37.56 and 36.03 per 100,000 persons, respectively. Gender difference in the prevalence of SLE was significant (P = 4.62 × 10(-76)), and the age-standardized prevalence was 6.17 for males and 67.78 for females per 100,000 persons. The distribution of SLE prevalence was significant by age group (P = 1.78 × 10(-53)), and the peak prevalence was observed at 40-50 years. Multiple environmental factors were associated with SLE, including birth conditions, sweet food, cooking oil, taste, fruit consumption, sunlight exposure, quality of sleep, physical activities, drinking water, residence, negative life events, hepatitis B vaccine, age of menarche, and age at birth of first child (P < 0.05). Our large population-based epidemiological survey estimated the prevalence of SLE at 37.56 per 100,000 persons. Multiple environmental factors were associated with the development of SLE.

Effects of alcohol on the composition and metabolism of the intestinal microbiota among people with HIV: a cross-sectional study.

OBJECTIVES: Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the faecal microbiota and its association with alcohol consumption in HIV-infected patients. METHODS: A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low to moderate drinking (n=21) and non-drinking (n=72) groups. RESULTS: Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low to moderate drinkinge group did not differ from that of the non-drinking group (all P>0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol, with Coprobacillus, Pseudobutyrivibrio and Peptostreptococcaceae enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional microbiome features were also found to be altered in the low to moderate drinking group, showing a reduction in metabolic pathways (P=0.036) and cardiovascular disease pathway (P=0.006). CONCLUSION: Low to moderate drinking will change the composition, metabolism and cardiovascular disease pathway of the gut microbiota of HIV-infected patients.

Association of P2X7R gene polymorphisms with systemic lupus erythematosus in a Chinese population.

The P2X7 receptor is a ligand-gated cationic channel receptor that is actived by ATP and normally expressed by a variety of immune system cells, including macrophages and lymphocytes. Because it leads to release of IL-1ß and cell death by apoptosis or necrosis, it is a potential therapeutic target for a variety of autoimmune inflammatory diseases, such as systemic lupus erythematosus (SLE). The P2X7R gene is highly polymorphic, and many single-nucleotide polymorphisms (SNPs) have been detected. A case-control study was performed to investigate the associations of SNPs in the P2X7R gene (rs1718119, rs2230911 and rs3751143) with susceptibility to SLE in 535 Chinese SLE patients and 532 controls. Results showed that rs1718119 was associated with SLE; in particular carriers of the A allele and AA/AG/(AG+AA) genotypes were at lower risk of the disease [A versus G, P < 0.001, odds ratio (OR) = 0.543, 95% CI: 0.424-0.697; AG versus GG, P = 0.018, OR = 0.659, 95% CI: 0.466-0.931; AA versus GG, P = 0.011, OR = 0.176, 95% CI: 0.046-0.668; AG+AA versus GG, P = 0.004, OR = 0.607, 95% CI: 0.433-0.850], but no significant differences in rs2230911 and rs3751143 were observed between SLE patients and controls. Stratification of cases for the presence of nephritis showed that rs2230911 G allele and CG/(CG+GG) genotypes were at a lower risk of SLE with nephritis (LN) (G versus C, P = 0.011, OR = 0.640, 95% CI: 0.454-0.903; CG versus CC, P = 0.035, OR = 0.645, 95% CI: 0.429-0.970; GG versus CC, P = 0.101, OR = 0.349, 95% CI: 0.099-1.228; CG+GG versus CC, P = 0.015 OR = 0.612, 95% CI: 0.411-0.910), but rs1718119 and rs3751143 were not associated with LN. Analysis of the haplotypes revealed one haplotype (ACA) that appeared to be a significantly 'protective' haplotype (P = 0.009, OR = 0.708, 95% CI: 0.546-0.918) with SLE. The findings suggest that the P2X7R gene might contribute to SLE susceptibility in the Chinese population.

Lack of association between IL-23R gene polymorphisms and systemic lupus erythematosus in a Chinese population.

OBJECTIVE: The aim to this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of interleukin (IL)-23 receptor gene and systemic lupus erythematosus (SLE) in a Chinese population. METHODS: A case-control study was performed to investigate the associations of SNPs in IL-23R gene (rs10889677 and rs1884444) with susceptibility to SLE in 521 Chinese SLE patients and 527 normal controls. The chi-square test and unconditional Logistic regression were used to analysis by SPSS 10.1 software. RESULTS: No significant differences were detected for the distribution of allele and genotype frequencies of these two SNPs between patients and controls as well as SLE patients with nephritis (LN) and those without nephritis. CONCLUSION: The findings suggest that the polymorphisms of IL-23R gene might not contribute to the susceptibility of SLE in the Chinese population.

CTLA-4 -1722T/C polymorphism and systemic lupus erythematosus susceptibility: a meta-analysis involving ten separate studies.

Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) -1722T/C polymorphism has been identified as a susceptibile gene for systemic lupus erythematosus (SLE), but studies are inconsistent. To better assess the association between CTLA-4 -1722T/C polymorphism and SLE, a meta-analysis was performed, including 10 studies, total of 1 387 patients and 1 617 controls. Overall, the CTLA-4 -1722T/C polymorphism was significantly associated with SLE susceptibility (T VS C: OR = 1.17, 95% CI = 0.86-1.60, P = 0.304; T/T VS C/C: OR = 1.92, 95% CI = 1.09-3.39, P = 0.024; T/C VS C/C: OR = 1.50, 95% CI = 0.91-2.49, P = 0.114; T/T VS T/C: OR = 1.29, 95% CI = 0.95-1.75, P = 0.107). When stratified by ethnicity, the CTLA-4 -1722T/C polymorphism was associated with SLE only in Asians (T VS C: OR = 1.47, 95% CI = 1.10-1.96, P = 0.010; T/T VS C/C: OR = 2.09, 95% CI = 1.13-3.85, P = 0.018; T/C VS C/C: OR = 1.53, 95% CI = 0.87-2.69, P = 0.141; T/T VS T/C: OR = 1.42, 95% CI = 0.97-2.09, P = 0.070). In summary, the CTLA-4 -1722T/C polymorphism confers to SLE risk, especially in Asians.