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Investigating the GWAS-Implicated Loci for Rheumatoid Arthritis in the Pakistani Population
Rheumatoid arthritis (RA) is a complex and multifactorial autoimmune disorder with the involvement of multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified more than 50 RA genetic loci in European populations. Given the anticipated overlap of RA-relevant genes and pathways across different ethnic groups, we sought to replicate 58 GWAS-implicated SNPs reported in Europeans in Pakistani subjects. 1,959 unrelated subjects comprising 1,222 RA cases and 737 controls were collected from three rheumatology facilities in Pakistan. Genotyping was performed using iPLEX or TaqMan® methods. A total of 50 SNPs were included in the final association analysis after excluding those that failed assay design/run or postrun QC analysis. Fourteen SNPs (LINC00824/rs1516971, PADI4/rs2240336, CEP57/rs4409785, CTLA4/rs3087243, STAT4/rs13426947, HLA-B/MICA/rs2596565, C5orf30/rs26232, CCL21/rs951005, GATA3/rs2275806, VPS37C/rs595158, HLA-DRB1/rs660895, EOMES/rs3806624, SPRED2/rs934734, and RUNX1/rs9979383) were replicated in our Pakistani sample at false discovery rate (FDR) of <0.20 with nominal values ranging from 4.73E-06 to 3.48E-02. Our results indicate that several RA susceptibility loci are shared between Pakistani and European populations, supporting the role of common genes/pathways.
Association of Serum FAM19A5 with Cognitive Impairment in Vascular Dementia
Objective. Family with sequence similarity 19 member A5 (FAM19A5), a novel chemokine-like peptide, is a secreted protein mainly expressed in the brain. FAM19A5 was recently found to be involved in a variety of neurological diseases; however, its correlation with vascular dementia (VaD) remains unclear. The aim of the study is to explore the association between serum FAM19A5 and cognitive impairment in subjects with VaD. Method. 136 VaD subjects and 81 normal controls were recruited in the study. Their demographic and clinical baseline data were collected on admission. All subjects received Mini-Mental State Examination (MMSE) evaluation, which was used to test their cognitive functions. A sandwich enzyme-linked immunosorbent assay (ELISA) was applied to detect the serum levels of FAM19A5. Results. No significant differences were found between the two groups regarding the demographic and clinical baseline data (). The serum FAM19A5 levels were significantly higher compared to normal controls (). The Spearman correlation analysis indicated that serum FAM19A5 levels and MMSE scores have a significant negative correlation in VaD patients (, <0.001). Further multiple regression analysis indicated that serum FAM19A5 levels were independent risk predictors for cognitive functions in VaD (, ). Conclusion. The serum FAM19A5 level of VaD patients is significantly increased, which may serve as a biomarker to predict cognitive function of VaD.
The Variation of Peripheral Inflammatory Markers in Vocal Leukoplakia before and after Recurrence and Canceration
Background. This retrospective study aims at comparing the variation of peripheral inflammatory markers in recurrent and cancerous vocal fold leukoplakia (VFL) and at exploring the potential connection with pathological outcomes. Methods. The patients undergoing carbon dioxide laser surgery with postoperative pathological diagnosis of recurrent vocal fold leukoplakia in the last 5 years were included. The clinical data were collected, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocytes-to-lymphocyte ratio (MLR) before and after recurrence and canceration were calculated. Related comparison with two-grade pathological classification was made to evaluate their potential connection with postsurgical histopathology and clinical events. Results. The data of 193 patients were engaged into research, as 111 in the recurrence group (Group A) and 82 in canceration group (Group B). The NLR, PLR, and MLR were significantly increased in canceration event compared to the first (, respectively) and penultimate (, respectively) time when the previous pathologies were leukoplakia. When redividing the Group A according to the two-grade pathological classification, the high-risk groups showed statistically higher NLR and PLR values than low-risk groups in the subgroups with grade changing (, respectively) and subgroups without grade changing (, respectively). Conclusions. NLR, PLR, and MLR are reliable biomarkers in the circulation system which show significantly interrelation with the pathological progression of vocal fold leukoplakia. Presurgical evaluation of NLR, PLR, and MLR may have potential values to indicate the following treatment in clinical practice.
Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy (with or without Chemotherapy) in Patients with Stage IB2, IIA, or IIB Cervical Cancer: A Systematic Review and Meta-Analysis
Background. This study was to compare the efficacy and safety between neoadjuvant chemotherapy followed by radical surgery (NACT+RS) and radiotherapy only (RT) or concurrent chemoradiotherapy (CCRT) for treatment of patients with stage IB2, IIA, or IIB cervical cancer. Method. The electronic databases of PubMed, Embase, and the Cochrane Library were searched to screen relevant studies from their inception to October 2018. Clinical data including overall survival (OS), disease-free survival (DFS), and adverse events were extracted. Egger’s test was used to evaluate the publication bias, and sensitivity analysis was conducted to estimate the robustness of results. Results. Finally, three randomized controlled trials (RCTs) and two case-control studies consisting of 1,275 patients with stage IB2, IIA, or IIB cervical cancer were included in the current study. Overall, pooled results showed no significant differences in OS ((, ) and DFS (, ) for patients treated with NACT+RS compared with RT only or CCRT, but the subgroup analysis showed that the OS and DFS were significantly longer in the NACT+RS groups than the RT or CCRT group (OS: , , ; DFS: , , ) for the population with median follow-up time of more than 60 months. For adverse events, the incidence of thrombocytopenia in the NACT+RS group was significantly higher than that in the RT only or CCRT group (, 95% CI 1.575-6.662), while the incidence of diarrhea was significantly lower than that in the RT only or CCRT group (, 95% CI =0.230-0.890). Conclusion. These findings suggest that the short-term therapeutic effects of the two treatments may be possibly equal for patients with stage IB2-IIB cervical cancer, but the long-term effects for improving OS and DFS may be better using NACT+RS compared with the RT only or CCRT.
Association of the Expression Level of miR-16 with Prognosis of Solid Cancer Patients: A Meta-Analysis and Bioinformatic Analysis
Objective. To assess the association between the expression level of miR-16 and prognosis of solid cancer patients by meta-analysis and bioinformatic analysis. Methods. PubMed, Web of Science, and Embase databases were searched until October 31, 2019, to identify eligible studies reporting the association of the miR-16 status with the prognosis of solid cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled, and a heterogeneity test was conducted. Sensitivity analysis and a publication bias test were also carried out. Furthermore, the miRpower database was used to validate the association. Results. Thirteen articles with 2303 solid cancer patients were included in the meta-analysis. Solid cancer patients with low expression level of miR-16 had shorter survival time (, , 95% CI: 1.13-1.91, ). In the subgroup analyses of cancer sites, low miR-16 expression level was associated with poor prognosis in the reproductive system cancers (, , 95% CI: 1.06-1.45, ). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg’s test and Egger’s test revealed no publication bias in the meta-analysis. In bioinformatic analysis, the significant association between miR-16 level and prognosis of patients with reproductive system cancers was further confirmed (, 95% CI: 1.03-1.42, ). Conclusion. Low expression level of miR-16 is an indicator for poor prognosis of solid cancer patients, particularly in reproductive system cancers.
Increased Serum Level and High Tissue Immunoexpression of Interleukin 17 in Cutaneous Lichen Planus: A Novel Therapeutic Target for Recalcitrant Cases?
Background. Interleukin-17 is supposed to play an important role in the pathogenesis of oral lichen planus (OLP). However, there is scarce data in the literature on its significance in the cutaneous variant of the disease. Objectives. To determine the serum level and tissue immunoexpression of IL-17 in cutaneous lichen planus (CLP). Methods. Fifty-two adult patients with CLP, without any significant autoimmune or inflammatory conditions, were included in the first part of the study. The control group consisted of 27 age- and sex-matched healthy volunteers. Serum concentration of IL-17 was quantified using enzyme-linked immunosorbent assay (ELISA) kit. In the second part of the study, the tissue expression of IL-17 was assessed in archival paraffin-embedded biopsy specimens from CLP () against normal control tissues () using immunohistochemical assays. The expression was evaluated using Zeiss Axio Imager A2 light microscope. Positively stained cells were counted in 10 fields of view for biopsy specimen at 200x magnification, and the mean value was calculated. Results. The serum level of IL-17 was significantly elevated in patients with CLP, compared with healthy volunteers ( versus , respectively; ). No correlation was found between the serum concentration of IL-17 and patient age, gender, disease duration, extent of skin involvement, the presence or intensity of pruritus, and coexistence of mucosal lesions. In tissue samples from CLP lesions, significantly higher numbers of cells expressing IL-17 were found when compared to a healthy skin (). Conclusion. Elevated serum concentration of IL-17 and high expression in a lesional skin support the hypothesis that IL-17 is implicated in the immunopathogenesis of CLP. These findings may constitute a premise for the future use of anti-IL-17 monoclonal antibodies in the treatment of severe and recalcitrant forms of CLP.