Man-Man Lu

Association of MicroRNA-146a with Autoimmune Diseases

MicroRNAs (miRNAs) are a group of approximately 20–22-nucleotide-long non-coding RNAs that repress target gene expression through mRNA degradation and translation inhibition. MiRNA (miR)-146a, located in the second exon of the LOC285628 gene on human chromosome 5, is a negative regulator in immune and inflammatory responses. Studies have indicated that miR-146a is associated with the pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s syndrome. In this review, emphasis will be laid on the recent progress in the functional roles of miR-146a in these autoimmune diseases.

Prognostic value of matrix metalloproteinase 9 expression in patients with non-small cell lung cancer

BACKGROUND The role of matrix metalloproteinase 9 (MMP-9) expression in non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review of the literature with meta-analysis. METHODS Electronic databases were used to identify published studies before December 1, 2011. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) was used to estimate the strength of the association between MMP-9 expression survival of NSCLC patients. Heterogeneity and publication bias were also assessed. RESULTS The final analysis of 2029 NSCLC cases from 17 studies is presented. The combined HR of 1.84 (95% CI: 1.62-2.09) suggested that MMP-9 over-expression had a poor prognosis in patients with NSCLC. Subgroup analyses also detected significant association. Heterogeneity and publication bias was absent in current meta-analysis. Sensitivity analyses suggested that the summary statistics obtained should approximate the actual average. CONCLUSION High MMP-9 expression is associated with a poor prognosis in patients with NSCLC.

Increased serum RANTES in patients with systemic lupus erythematosus

The aim of this study was to investigate the serum RANTES (regulated on activation, normal T-cell expressed and secreted) level in patients with systemic lupus erythematosus (SLE), and the associations with disease activity and clinical laboratory indexes. Twenty-seven SLE patients and 27 normal controls were enrolled in this study. Serum RANTES was measured by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory parameters of the patients were also recorded. Results showed that serum RANTES level was significantly elevated in SLE patients when compared with normal controls. Serum RANTES level was correlated with C3, ANA, anti-dsDNA antibodies, anti-Sm antibodies, and anti-SSB antibodies. Nevertheless, no association of serum RANTES level with SLEDAI was found. Taken together, serum RANTES level was significantly higher in SLE patients, suggesting that RANTES might be involved in the pathogenesis of SLE.

Association of FAS gene polymorphisms with systemic lupus erythematosus: A case-control study and meta-analysis

The association of functional polymorphisms in the promoter of the apoptosis gene FAS with systemic lupus erythematosus (SLE) susceptibility has been a controversial subject. We conducted a case-control study to investigate this association in a Chinese population and performed a meta-analysis in different populations. The single nucleotide polymorphisms (SNPs) rs2234767 (−1377G>A) and rs1800682 (−670A>G) were genotyped by TaqMan allelic discrimination assays in 552 Chinese SLE patients and 718 healthy controls. In our case-control study, we observed allelic association between the promoter SNP rs2234767 [P=0.033, odds ratio (OR)=0.836, 95% confidence interval (CI), 0.709–0.986] and SLE but not the SNP rs1800682. Haplotype analysis revealed that one haplotype of GA was significantly associated with the disease (P=0.039, OR=1.184, 95% CI, 1.009–1.391). In the meta-analysis available studies, including our data, were combined using the STATA software package v.7.0. The meta-analysis revealed a significant association between FAS polymorphisms and SLE (rs2234767 A vs. G allele; P=0.004, OR=0.819, 95% CI, 0.715–0.938, rs1800682 G vs. A allele: P=0.034, OR=0.791, 95% CI, 0.637–0.983). In conclusion, FAS gene polymorphisms may contribute to SLE susceptibility in the Chinese population, and the meta-analysis shows that FAS polymorphisms may be associated with SLE susceptibility in different populations.

MicroRNA-101, mitogen-activated protein kinases and mitogen-activated protein kinases phosphatase-1 in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the prototype of human autoimmune disease in which various inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6 and interferon (IFN) play crucial pathogenic roles. The production of these cytokines is responsible for the mitogen-activated protein kinases (MAPKs), which can also generate mitogen-activated protein kinases phosphatases (MKPs). MKP-1, a prototypical member of the MKP family that can influence outcomes of autoimmune diseases and reduce the inflammatory cytokines by dephosphorylation of p38 and JNK MAPK, plays a critical role in the expression of inflammatory mediators at transcriptional and post-transcriptional levels. MicroRNA-101 (miR) is a small non-coding RNA that regulates the MAPK response by targeting MKP-1 mRNA 3′-UTR, and affects the secretion of the downstream inflammatory cytokines. However, the interaction among the above three in the pathogenesis of SLE has not previously been reported. This review discusses the current understanding of the role of the MAPK/MKP/miR-101 axis in regulating immune responses and the pathogenesis of SLE to provide new ideas for clinical treatment of SLE.

Association of RIP2 gene polymorphisms and systemic lupus erythematosus in a Chinese population.

The aim of this study was to investigate the association of receptor interacting protein 2 (RIP2) single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A case-control study was performed on the SNPs rs16900617 and rs16900627 in 590 Chinese SLE patients and 660 healthy controls. These SNPs were typed by TaqMan allele discrimination assays. We found a significant association of rs16900617 G allele [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.41-0.72] and rs16900627 G allele (OR = 1.28, 95% CI 1.04-1.58) with SLE. Significant differences in genotype frequency distribution were also found in SLE and control individuals (rs16900617: AG versus AA, OR = 0.59, 95% CI 0.44-0.81; GG versus AA, OR = 0.08, 95% CI 0.01-0.65; AG + GG versus AA, OR = 0.55, 95% CI 0.41-0.75; rs16900627: AG versus AA, OR = 1.51, 95% CI 1.17-1.93; AG + GG versus AA, OR = 1.43, 95% CI 1.13-1.82). Analysis of the haplotypes revealed that two haplotypes of AG and GA were also significantly associated with SLE (OR = 1.37, 95% CI 1.11-1.70; OR = 0.60, 95% CI 0.45-0.79). Our findings suggest that the RIP2 gene polymorphisms may be associated with susceptibility to SLE in the Chinese population.

Sex‐specific differences in the relationship between the single‐nucleotide polymorphism rs2298804 of FCER1A and the susceptibility to systemic lupus erythematosus in a Chinese Han population

IgE plays a important role in systemic lupus erythematosus (SLE). A recent study identified the high‐affinity IgE receptor α‐chain (FcεRIα) gene FCER1A as a susceptibility locus influencing total serum IgE levels.

The relationship between demands for lung cancer screening and the constructs of health belief model: a cross-sectional survey in Hefei, China

Abstract The aim of investigation is to explore the relationship between demands for lung cancer screening (LCS) and the constructs derived from the health belief model (HBM) in Hefei. The study collected data about socio-demographics, health beliefs in and demands for LCS during early June to later July 2015. By constructing a LCS demands HBM constructs, it calculated indices of demands for LCS (DSI) and HBM constructs, which include perceived risk (PR) and seriousness (PS) of the cancers; and perceived effectiveness (PE), benefits (PB) and difficulties (PD) of the screening. It also performed descriptive and multivariate regression analysis of the demands and the HBM constructs. The amount of 823 respondents participated and completed the survey. 6.4% of them had ever undertaken LCS, whereas 60.1% of them expressed willingness to accept the service of LCS if it is free. In multiple regression analysis which used weights in calculating the HBM construct indices, education displayed significant positive associations with DSI (p = .044), and most of HBM constructs indices (PSI, PRI, PBI, and PDI) were statistically significant with DSI (p < .05). HBM-based constructs regarding LCS have important effects on demands for the service, and may provide effective paths to cancer screening promotion.

Pathways and cost-effectiveness of routine lung cancer inpatient care in rural Anhui, China: a retrospective cohort study protocol

Introduction Routine inpatient care (RIC) for patients with cancer forms various pathways of clinical procedures. Although most individual procedures comprising the pathways have been tested via clinical trials, little is known about the collective cost and effectiveness of the pathways as a whole. This study aims at exploring RIC pathways for patients with lung cancer from rural Anhui, China, and their determinants and economic impacts. Methods and analysis The study adopts a retrospective cohort design and proceeds in five steps. Step 1 defines the four main categories of study variables, including clinical procedures, direct cost and effectiveness of procedures, and factors affecting use of these procedures and their cost and effectiveness. Step 2 selects a cohort of 5000 patients with lung cancer diagnosed between 1 July 2015 and 30 June 2016 from rural Anhui by clustered random sampling. Step 3 retrieves the records of all the inpatient care episodes due to lung cancer and extracts data about RIC procedures, proximate variables (eg, Karnofsky Performance Status, Lung Function Score) of patient outcomes and related factors (eg, stage of cancer, age, gender), by two independent clinician researchers using a web-based form. Step 4 estimates the direct cost of each of the RIC procedures using micro-costing and collects data about ultimate patient outcomes (survival and progression-free survival) through a follow-up survey of patients and/or their close relatives. Step 5 analyses the data collected and explores pathways of RIC procedures and their relations with patient outcomes, costs, cost:effect ratios, and a whole range of clinical and sociodemographic factors using multivariate regression and path models. Ethics and dissemination The study protocol has been approved by an authorised ethics committee of Anhui Medical University (reference number: 20170312). Findings from the study will be disseminated through conventional academic routes such as peer-reviewed publications and presentations at regional, national and international conferences. Trial registration number ISRCTN25595562.