Rapid and Sensitive Detection of Fentanyl and Its Analogs by a Novel Chemiluminescence Immunoassay.

BACKGROUND: Abuse of fentanyl and its analogs is a major contributor to the opioid overdose epidemic in the United States, but detecting and quantifying trace amounts of such drugs remains a challenge without resorting to sophisticated mass spectrometry-based methods. METHODS: A sensitive immunoassay with a sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high-affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When used with human urine samples, the assay has a sub-picogram limit of detection for fentanyl, with results fully concordant with LC-MS. RESULTS: When applied to clinical samples, the novel chemiluminescence immunoassay can detect low positive fentanyl missed by routine screening immunoassays, with a limit of detection of 0.8 pg/mL in human urine. When applied to environmental samples, the assay can detect levels as low as 0.25 pg fentanyl per inch2 of environment surface. Assay turnaround time is less than 1 h, with inexpensive equipment and the potential for high-throughput automation or in-field screening. CONCLUSIONS: We have established a novel assay that may have broad applications in clinical, environmental, occupational, and forensic scenarios for detection of trace amounts of fentanyl and its analogs.

Growth of infants delivered by mothers with HIV in Guangxi, China: An 18-month longitudinal follow-up study, 2015-2021.

OBJECTIVES: The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. METHODS: We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. RESULTS: Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.

MiCas9 increases large size gene knock-in rates and reduces undesirable on-target and off-target indel edits.

Gene editing nuclease represented by Cas9 efficiently generates DNA double strand breaks at the target locus, followed by repair through either the error-prone non-homologous end joining or the homology directed repair pathways. To improve Cas9's homology directed repair capacity, here we report the development of miCas9 by fusing a minimal motif consisting of thirty-six amino acids to spCas9. MiCas9 binds RAD51 through this fusion motif and enriches RAD51 at the target locus. In comparison to spCas9, miCas9 enhances double-stranded DNA mediated large size gene knock-in rates, systematically reduces off-target insertion and deletion events, maintains or increases single-stranded oligodeoxynucleotides mediated precise gene editing rates, and effectively reduces on-target insertion and deletion rates in knock-in applications. Furthermore, we demonstrate that this fusion motif can work as a "plug and play" module, compatible and synergistic with other Cas9 variants. MiCas9 and the minimal fusion motif may find broad applications in gene editing research and therapeutics.

Rate of the HIV Transmission and Associated Factors Among HIV-Exposed Infants in Guangxi, China: 2014-2019.

This study aims to evaluate the epidemiological characteristics of mother-to-child transmission (MTCT) of HIV and identify the possible factors leading to infant HIV infection using a retrospective cohort study of early infant diagnosis (EID). Information on a total of 3,145 exposed infant-mother pairs was collected from the EID platform from July 2014 to December 2019. The MTCT rate was 2.1%. Spatial-temporal maps showed that rates varied by year and by region, with four districts (Baise, Guigang, Guilin, and Hechi) maintaining rates of >2.0% in 2019. The rate of antiretroviral therapy (ART) use was 94.4%, with a gradual increase in prescriptions of highly active ART (HAART) from 83.0% in 2014 to 92.4% in 2019. A majority of 99.5% of infants were receiving artificial feeding. Factors associated with MTCT were ART use (odds ratio [OR] = 0.065, confidence interval [95% CI] = 0.035-0.121) and artificial feeding (OR = 0.091, 95% CI = 0.018-0.452). HAART was more helpful in decreasing the risk of MTCT compared with monotherapy (OR = 0.115, 95% CI = 0.014-0.933). ART during the postpartum period correlated with an increased risk (OR = 11.579, 95% CI = 1.402-95.960) compared with use of ART during pregnancy. This study indicates that MTCT rate of HIV is decreasing meaningfully in Guangxi. Some areas still face challenges in elimination of MTCT and need further resources and interventions. Future program planning should take into consideration the fact that ART use-in particular the use of HAART or ART during pregnancy-and replacement feeding may contribute to the prevention of MTCT.

Human IgA Monoclonal Antibodies That Neutralize Poliovirus, Produced by Hybridomas and Recombinant Expression.

Poliovirus (PV)-specific intestinal IgAs are important for cessation of PV shedding in the gastrointestinal tract following an acute infection with wild type or vaccine-derived PV strains. We sought to produce IgA monoclonal antibodies (mAbs) with PV neutralizing activity. We first performed de novo IgA discovery from primary human B cells using a hybridoma method that allows assessment of mAb binding and expression on the hybridoma surface: On-Cell mAb Screening (OCMS™). Six IgA1 mAbs were cloned by this method; three potently neutralized type 3 Sabin and wt PV strains. The hybridoma mAbs were heterogeneous, expressed in monomeric, dimeric, and aberrant forms. We also used recombinant methods to convert two high-potency anti-PV IgG mAbs into dimeric IgA1 and IgA2 mAbs. Isotype switching did not substantially change their neutralization activities. To purify the recombinant mAbs, Protein L binding was used, and one of the mAbs required a single amino acid substitution in its κ LC in order to enable protein L binding. Lastly, we used OCMS to assess IgA expression on the surface of hybridomas and transiently transfected, adherent cells. These studies have generated potent anti-PV IgA mAbs, for use in animal models, as well as additional tools for the discovery and production of human IgA mAbs.

Long non­coding RNA BCYRN1 promotes glycolysis and tumor progression by regulating the miR­149/PKM2 axis in non­small­cell lung cancer.

Cancer cells use aerobic glycolysis to sustain their proliferation. Long non­coding RNA brain cytoplasmic RNA 1 (BCYRN1) has been reported to act as an oncogene in non­small­cell lung cancer (NSCLC). The present study investigated the role of BCYRN1 in NSCLC glycolysis. BCYRN1 expression was detected in NSCLC cells and tissues using reverse transcription­quantitative PCR. The effect of BCYRN1 on aerobic glycolysis was examined by measuring NSCLC cell glucose catabolism and lactate synthesis. The relationships between BCYRN1 and microRNA (miR)­149, and between miR­149 and pyruvate kinase M1/2 (PKM2) were measured using a dual­luciferase reporter assay. Cell proliferation and invasion were analyzed by the Cell Counting kit­8 assay and the Matrigel invasion assay, respectively. High BCYRN1 expression was observed in NSCLC tissues and cells compared with the corresponding controls. BCYRN1 induced glycolysis and upregulated the expression levels of PKM2 in NSCLC cells. In addition, BCYRN1 regulated miR­149 expression levels, and miR­149 inhibitor rescued the effects of si­BCYRN1 on glucose consumption and lactate production. miR­149 knockdown significantly enhanced the expression of PKM2. Furthermore, PKM2 inhibition significantly reversed the effects of miR­149 inhibitor on glucose catabolism and lactate synthesis. Furthermore, PKM2 was involved in NSCLC cell proliferation and invasion, and BCYRN1 knockdown and miR­149 overexpression inhibited both processes. The present study suggested that BCYRN1 was involved in cell glycolysis, proliferation and invasion during NSCLC via regulating miR­149 and PKM2.

The Role of Killer Immunoglobulin-Like Receptor Genes in Susceptibility to HIV-1 Infection and Disease Progression: A Meta-Analysis.

Genetic studies on the association of the killer immunoglobulin-like receptor (KIR) genes with HIV-1 infection and disease progression have been widely carried out with somewhat contradictory results. Therefore, we undertook a quantitative assessment based on 25 studies [involving 3,216 HIV-1 infected subjects, 1,690 exposed uninfected subjects, 1,262 healthy controls (HCs), 748 typical progressors (TPs), and 244 long-term nonprogressors (LTNPs)] to further define the roles of KIR in HIV-1 control/susceptibility. An overall analysis, showed that, among the 16 KIR genes, the presence of KIR2DS4 may associate with an elevated risk of HIV-1 infection (p < .05, using HCs), whereas KIR3DS1 may associate with a reduced risk (p < .001, using HCs). In the subgroup analyses, among Africans, KIR2DS4 also revealed a significant risk of HIV-1 infection (p < .05), whereas KIR2DL2, 2DL5, and 2DS3 conferred a protective role (p < .05). KIR2DL2 and 3DL1 showed an increased risk of acquiring infection among Caucasians (p < .05). A negative effect on susceptibility to infection for KIR2DL1, 2DL3, and 3DS1 was found among East Asians. 3DS1 conferred a protective effect of HIV-1 infection among serodiscordant couples (p < .05). Moreover, among Chinese, KIR2DL3 was significantly lower in frequency in TPs when compared with LTNPs (p < .05), indicating a possible role in the delay of disease progression. This meta-analysis supports the individual studies that associate specific KIR genes with HIV-1 infection and disease progression and further emphasizes that this outcome differs according to specific populations.

Role of SDF-1 3'A polymorphism in HIV-1 disease progression: A systematic review and meta-analysis.

BACKGROUND: Chemokine stromal cell-derived factor 1(SDF-1) 3'A polymorphism has been reported to influence HIV-1 disease pathogenesis and progression, but the results remain controversial. OBJECTIVES: A meta-analysis was carried out to evaluate their association. METHODS: Comprehensive literature search of Pubmed, Web of Science and China National Knowledge Infrastructure was conducted. The strength of association between SDF-1 3'A polymorphism and HIV-1 progression was evaluated using the pooled ORs and 95%CIs calculated under different comparison models. Subgroup analyses, heterogeneity, Galbraith plot analyses and test for publication bias were also carried out. RESULTS: Our result showed that when compared with the typical progressors, the GA + AA and GA genotype of SDF-1 3'A polymorphism was found positively associated with the long-term non-progressors (LTNP) in the Caucasian HIV-1 infectors (GA + AA vs. GG, OR = 1.49, 95% CI: 1.02-2.18, p = 0.040; GA vs. GG, OR = 1.58, 95% CI: 1.06-2.35, p = 0.024), while AA genotype was found significantly higher in Asian LTNPs (AA vs. GG + GA, OR = 3.32, 95% CI: 1.25-8.85, p = 0.016). CONCLUSIONS: Our result suggested that HIV-1 infectors with SDF-1 3'A polymorphism have a higher chance of developing late AIDS than infectors with the SDF-1 GG genotype.

Systematic review and meta-analysis of single-incision versus conventional multiport laparoscopic splenectomy.

BACKGROUND: There is no consensus that single-incision laparoscopic surgery splenectomy (SILS-SP) is on a par with conventional multiport laparoscopic surgery splenectomy (CMLS-SP). AIMS: The aim of this systematic review and meta-analysis was to assess feasibility and safety of SILS-SP when compared with CMLS-SP. MATERIALS AND METHODS: Eligible articles were identified by searching several databases including PubMed, EMBASE, CNKI (China) and the Cochrane Library, up until February 2016. Studies were reviewed independently and rated by Newcastle-Ottawa Quality Assessment Scale. Evaluated outcomes were complications, operative time, post-operative hospital stay, blood loss, starting diet, post-operative pain scores, conversion and analgesic requirements. RESULTS: Ten retrospective studies met the eligibility criteria. Overall, there was no significant difference between SILS-SP and CMLS-SP in complications, operative time, post-operative hospital stay, blood loss, starting diet, post-operative pain scores, conversion and analgesic requirements. CONCLUSIONS: SILS-SP is feasible and safe in certain patients, with no obvious advantages over CMLS-SP. Therefore, it may be considered an alternative to CMLS-SP. We await high-quality, double-blind RCTs. These should include clear statements on standard scores of post-operative pain and cosmetic results, longer follow-up assessment and cost-benefit analysis.

Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis.

INTRODUCTION: The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies. METHODS: All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study. RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks. CONCLUSIONS: Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke.

Activation of Mouse Tcrb: Uncoupling RUNX1 Function from Its Cooperative Binding with ETS1.

T lineage commitment requires the coordination of key transcription factors (TFs) in multipotent progenitors that transition them away from other lineages and cement T cell identity. Two important TFs for the multipotent progenitors to T lineage transition are RUNX1 and ETS1, which bind cooperatively to composite sites throughout the genome, especially in regulatory elements for genes involved in T lymphopoiesis. Activation of the TCR ß (Tcrb) locus in committed thymocytes is a critical process for continued development of these cells, and is mediated by an enhancer, Eß, which harbors two RUNX-ETS composite sites. An outstanding issue in understanding T cell gene expression programs is whether RUNX1 and ETS1 have independent functions in enhancer activation that can be dissected from cooperative binding. We now show that RUNX1 is sufficient to activate the endogenous mouse Eß element and its neighboring 25 kb region by independently tethering this TF without coincidental ETS1 binding. Moreover, RUNX1 is sufficient for long-range promoter-Eß looping, nucleosome clearance, and robust transcription throughout the Tcrb recombination center, spanning both DßJß clusters. We also find that a RUNX1 domain, termed the negative regulatory domain for DNA binding, can compensate for the loss of ETS1 binding at adjacent sites. Thus, we have defined independent roles for RUNX1 in the activation of a T cell developmental enhancer, as well as its ability to mediate specific changes in chromatin landscapes that accompany long-range induction of recombination center promoters.

Plasminogen Activator Inhibitor-1 Polymorphism Confers a Genetic Contribution to the Risk of Recurrent Spontaneous Abortion: An Updated Meta-Analysis.

Various studies have investigated the risk of recurrent spontaneous abortion (RSA) with plasminogen activator inhibitor-1 ( PAI-1) 4G/5G polymorphism. However, the results have been somewhat contradictory. Therefore, an updated meta-analysis based on 31 studies (5617 cases and 3952 controls) was undertaken to clarify this relationship. The degree of RSA risk was estimated using the odds ratio (OR) and the 95% confidence interval (CI). Overall, the random effects OR was 1.464 (95% CI: 1.269-1.690) for 4G versus 5G, 2.075 (95% CI: 1.563-2.754) for 4G/4G versus 5G/5G, 1.457 (95% CI: 1.211-1.753) for 4G/5G versus 5G/5G, 1.743 (95% CI: 1.358-2.236) for 4G/4G versus 4G/5G + 5G/5G, and 1.600 (95% CI: 1.327-1.930) for 4G/4G + 4G/5G versus 5G/5G, indicating that PAI-1 4G/5G polymorphism could confer an increased risk of RSA. Furthermore, a subgroup analysis showed a significantly elevated susceptibility to RSA in Asians, Caucasians, and Africans. Thus, this study demonstrated that PAI-1 4G/5G polymorphism likely confers a genetic contribution to the development of RSA. The results may aid in developing a theoretical basis for effective strategies to prevent and treat RSA.

cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer Independent.

Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritize transcriptional control elements as therapeutic targets.

P-glycoprotein gene MDR1 polymorphisms and susceptibility to systemic lupus erythematosus in Guangxi population: a case-control study.

The multidrug resistance 1 gene (MDR1) encodes for P-glycoprotein (P-gp), which plays a pathophysiological role in the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Herein, we aimed to investigate the relationship between MDR1 gene polymorphisms and SLE susceptibility in the Chinese Guangxi population. The genotypes of rs1128503 and rs1045642 in MDR1 gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method in 283 SLE patients and 247 healthy controls from Guangxi. Direct sequencing method was used to verify the results. Binary logistic regression analyses adjusting for gender and age indicated that subjects carrying the rs1128503 T-allele and TT genotype were at increased risk of SLE when compared to carriers of the C allele and CC genotype, with adjusted ORs of 1.36 (95% CI 1.07-1.74; P = 0.014) and 1.77 (95% CI 1.08-2.88; P = 0.022), respectively. In addition, the risk allele T had a recessive effect (OR 1.49, 95% CI 1.04-2.14, P = 0.029). Subgroup analyses revealed effect modification by age for the presence of the rs1128503 T allele, yielding a significant positive association with SLE in older (≥40 years) subjects (T vs. C allele: OR 1.41, 95% CI 1.01-1.96; P = 0.041; TT vs. CC genotype: OR 1.74, 95% CI 1.07-2.79; P = 0.021). For the first time, we demonstrated that MDR1 rs1128503 polymorphisms were associated with SLE susceptibility in Chinese Guangxi population.

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study.

OBJECTIVE: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC). METHOD: A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005). CONCLUSIONS: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

Laparoendoscopic Single-site Adrenalectomy versus Conventional Laparoscopic Adrenalectomy: An Updated Meta Analysis.

PURPOSE: Previous meta-analyses that compared the outcome of laparoendoscopic single-site adrenalectomy (LESSA) and conventional laparoscopic adrenalectomy (CLA) have not shown consistent results. The aim of this meta-analysis was to reassess current evidence regarding the efficacy and safety of LESSA versus CLA. MATERIALS AND METHODS: A literature search of PubMed, Embase, Medline, and the Cochrane Library was performed to identify eligible articles up until September 2015. Quantitative variables were calculated using the weighted mean differences (WMDs), and qualitative variables were pooled using odds ratios (ORs). RESULTS: Ten retrospective studies, including a total of 704 cases, were identified. Patients in the LESSA group benefitted from shorter length of hospital stay (95% confidence interval [CI]: -1.27 to -0.36, WMD: -0.81, P < .001) and better postoperative pain scores (95% CI: -1.51 to -0.99, WMD: 1.25, P < .001). There was no significant difference between the two techniques in operative time, estimated blood loss, resumption of oral intake, dose of analgesic required, perioperative complications, conversion, transfusion, or pain medications required. CONCLUSIONS: Based on current evidence, LESSA appear to be a safe and feasible alternative to CLA with a shorter length of hospital stay and lower postoperative pain scores in certain patients. We await high-quality, double-blind randomized clinical trials with long-term follow-up to confirm and update the findings of this analysis; future studies should focus on failure of technique, cosmesis, and cost.

The Effects of RANTES Polymorphisms on Susceptibility to HIV-1 Infection and Disease Progression: Evidence from an Updated Meta-Analysis.

Associations of regulated on activation, normal T cell expressed and secreted (RANTES) -403G/A, -28C/G, and In1.1T/C polymorphisms with HIV-1 infection and the progression of HIV-1 disease have been widely reported with inconsistent results. To clarify this situation, we performed an updated meta-analysis of all available studies from PubMed, EMBASE, and the China National Knowledge Infrastructure. A total of 24 eligible studies involving more than 10,000 subjects were included. By using the healthy controls, we found that -403G/A polymorphism was significantly associated with reduced susceptibility to HIV-1 infection in G/A+A/A versus GG (odds ratio [OR] = 0.755, 95% confidence interval [CI] = 0.581-0.982); and a significantly decreased risk was also found for -28C/G polymorphisms (G vs. C, OR = 0.804, 95% CI = 0.696-0.927; G/G+C/G vs. C/C, OR = 0.826, 95% CI = 0.704-0.969). Whereas for In1.1T/C polymorphism, increased risk of HIV-1 infection was revealed (C vs. T, OR = 1.216, 95% CI = 1.047-1.430; T/C vs. T/T, OR = 1.68, 95% CI = 1.263-2.234; T/C+T/T vs. C/C, OR = 1.466, 95% CI = 1.147-1.875). Subgroup analyses by ethnicity showed significant association among Asians, but not among Caucasians. When HIV-1-exposed seronegative (HESN) controls were used, no significant association was detected. Moreover, -403G/A and -28C/G polymorphisms were also not associated with long-term nonprogressive HIV-1 infection (all p > .05). This meta-analysis suggests that RANTES -403G/A and -28C/G polymorphisms confer possible protection against HIV-1 infection, whereas In1.1T/C polymorphism may increase risk of HIV-1 infection, especially in Asians. These results may contribute to finding a theoretical basis for effective control strategies against HIV/AIDS. Further investigations are needed to validate our conclusions.

A pooled analysis of the IL-10-1082 A/G polymorphism and the nasopharyngeal carcinoma susceptibility.

It has been reported that IL-10-1082 A/G polymorphism might influence the transcription and secretion of IL10 and tumor development. While many studies have been conducted to investigate the association between IL-10-1082 A/G polymorphism and risk of nasopharyngeal carcinoma (NPC) in various populations, the results of these studies are still controversial. We aimed to explore this relationship through a cumulative meta-analysis. A search of the literature was performed using the Cochrane Library, PubMed, and EMBASE databases. The odds ratio (OR) and corresponding 95 % confidence interval (CI) were calculated to assess this possible association. Six studies were included in the study. The meta-analysis reveals a significant effect in the allelic model (G vs. A: OR 1.516, 95 % CI 1.077-2.133, P heterogeneity = 0.003), dominant model (AG + GG vs. AA: OR = 1.770, 95 % CI 1.415-2.212, P heterogeneity = 0.169), and co-dominant model (AG vs. AA: OR = 1.747, 95 % CI 1.377-2.216, P heterogeneity = 0.491). Similarly, in the stratified analyses, significant effects were reported in studies of Asian populations. Our meta-analysis results suggest that the IL-10-1082 A/G variant is associated with increased risk of NPC in Asian populations.

Association between catalase gene polymorphisms and risk of chronic hepatitis B, hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma in Guangxi population: a case-control study.

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC). A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms. Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04-2.20, P = 0.029), 1.48 (95% CI = 1.03-2.14, P = 0.035), and 1.51 (95% CI = 1.14-1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05-4.22, P = 0.035), 2.00 (95% CI, 1.01-3.95, P = 0.047), and 1.93 (95% CI = 1.14-3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16-2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23-2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05-2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52-0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases. Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.

The CD4 C868T Polymorphism and Its Correlation with HIV-1 Infection in a Chinese Population.

Previous studies performed in Kenya have suggested that the C868T single nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition; however, no relevant study has been conducted in China. To evaluate the influence of this SNP on risk of HIV-1 infection in a Chinese population, the CD4 genotype was determined by DNA sequencing in 101 HIV-1 patients and 102 healthy controls. No significant differences in the genotype and allele distributions of this polymorphism were observed among the patient and control groups. Additionally, binary logistic regression analyses adjusted by age and gender revealed that the C868T polymorphism was not associated with risk of HIV-1 infection. Furthermore, when analyses of genotype and allele frequencies were stratified by gender, similar nonsignificant results were found. Our study demonstrates a null association between the CD4 C868T polymorphism and an individual's susceptibility of HIV-1 acquisition in a Chinese population. Further studies are warranted to confirm these results.