Search

ABSTRACTHepatic immunity is one of the driving forces for the development of nonalcoholic steatohepatitis (NASH), and targeting gut microbiota is believed to affect the hepatic immune constitution. Here, we aimed to investigate the hepatic immunological state in NASH, with a specific emphasis on natural killer (NK) cells. In addition, we aimed to identify the contributing species that target hepatic immunity to provide new directions and support the feasibility of immunotherapy for NASH. A possible NASH population was determined by combination of long-term severe fatty liver, metabolic disorders and increased serum CK18 to detect serum immune factors and gut microbiota. NASH was induced in mice fed a high-fat diet to verify the prophylactic effect of the functional species on the immunopathology and development of NASH. Hepatic immunologic state was examined, and the effector functions of NK cells were detected. Hepatic transcriptome, proteomic, and fecal metagenome were performed. We observed a statistical increase in serum IL-10 (p

Abstract Purpose To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities. Methods We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression. Results During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30–40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD. Conclusions FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30–40 and female populations above 60 for FLD prevention and treatment.

Abstract Interferon-γ release assay (IGRA) is a widely used blood test for detecting TB infection. However, a positive result of IGRA cannot differentiate active tuberculosis (ATB) infection from inactive tuberculosis (IATB). In this study, we established a nomogram model for predictive risk of ATB, differentiated from IATB, based on the concentration of interferon-γ (IFN-γ) of QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and clinical characteristics. Participants with a positive QFT-GIT result were recruited and divided into a training and validation cohort according to hospitalisation date. The nomogram model for the differential diagnosis of ATB from IATB was established according to gender, age, pleural effusion (PE), and the concentration of IFN-γ in the Nil, TB antigen, and mitogen tube of QFT-GIT in the training cohort by logistic regression and validated in the validation cohort, and then combined with adenosine deaminase (ADA) to evaluated the performance value in ATB cases with PE. The area under receiver operating characteristic curve (AUC) of the diagnostic nomogram model, which we called the NSMC-ATB model for ATB diagnosis was 0.819 (95% CI 0.797–0.841), with sensitivity 73.16% and specificity 75.95% in training cohort, and AUC was 0.785 (95% CI 0.744–0.827), with sensitivity 67.44% and specificity 75.14% in validation cohort. A combination of the NSMC-ATB model and ADA performed better than the NSMC-ATB model and ADA alone in predicting ATB cases with PE, as AUC was 0.903 (95% CI 0.856–0.950) with sensitivity 78.63% and specificity 87.50%. We established an effective diagnostic nomogram model, called the NSMC-ATB model to differentiate ATB from IATB. Meanwhile, the combination of the NSMC-ATB model and ADA improved the performance value of ATB with PE.

Abstract Objectives Dysglycemia promotes the occurrence of fatty liver disease (FLD). However, the process is unclear. This study aimed to analyze the median time-to-onset, cumulative prevalence and influencing factors for the occurrence of FLD in people undergoing routine screening and evaluation. Methods Data from Karamay Central Hospital (September 2008–April 2017) were analyzed. Survival analysis was performed to calculate the median time and cumulative prevalence of FLD associated with normal and elevated fasting blood glucose (FBG) levels. Cox proportional hazards model was used to determine risk factors. Results A total of 31,154 participants were included in the two cohorts of this study, including 15,763 men. The mean age was 41.1 ± 12.2 years. There were 2230 patients (1725 male) in the elevated FBG group, the median age was 53 years (range 21–85 years), the median time-to-onset of FLD was 5.2 years. The incidence of FLD was 121/1000 person-years, and the 1-, 3-, 5-, and 7-year prevalence rates were 4%, 30%, 49%, and 64%, respectively. The normal FBG group included 28,924 participants (14,038 male), the median age was 40 years (range 17–87 years), and the corresponding values were as follows: 8.3 years, 66/1000 person-years, and 3%, 16%, 28%, and 41%, respectively. The Cox proportional hazards analysis revealed that age, blood pressure, FBG, body mass index and triglycerides were independent influencing factors for FLD in individuals (P

Abstract Background Recent studies have shown that chronic kidney disease (CKD) prevalence is significantly higher in patients with hepatic steatosis (HS); however, it remains unclear whether HS is associated with serum creatinine (SCr). We aimed to explore the association between SCr levels and HS in a Chinese population. Methods We performed a cross-sectional study among 56,569 Chinese individuals. SCr level, other clinical and laboratory parameters, abdominal ultrasound and noninvasive fibrosis scores were extracted, and the fibrosis 4 score (FIB-4) was calculated. Results A total of 27.1% of the subjects had HS. After 1:1 propensity score matching (PSM) according to sex and age, we included 13,301 subjects with HS and 13,301 subjects without HS. SCr levels were significantly higher in the HS group than in the non-HS group [73.19 ± 15.14(μmoI/L) vs. 71.75 ± 17.49(μmoI/L), p

Background: Considering the remarkable heterogeneity of biological features of renal cell carcinoma (RCC), the current clinical classification that only relies on classic clinicopathological features is in urgent need of improvement. Herein, we aimed to conduct DNA methylation modification patterns in RCC. Methods: We retrospectively curated multiple RCC cohorts, comprising TCGA-KIRC, TCGA-KICH, TCGA-KIRP, and E-MTAB-1980. DNA methylation modification patterns were proposed with an unsupervised clustering algorithm based on 20 DNA methylation regulators. Immunological features were characterized using tumor-infiltrating immune cells and immunomodulators. Sensitivity to immuno- or targeted therapy was estimated with submap and Genomics of Drug Sensitivity in Cancer (GDSC). DNA methylation score (DMS) was developed with principal component analysis. Results: Three DNA methylation modification patterns were conducted across RCC patients, namely C1, C2 and C3. Among them, C3 displayed the most remarkable survival advantage. The three patterns presented in agreement with immune phenotypes: immune-desert, immune-excluded, and immune-inflamed, respectively. These patterns displayed distinct responses to anti-PD-1 and targeted drugs. DMS enabled the quantification of DNA methylation status individually as an alternative tool for prognostic estimation. Conclusions: The DNA methylation molecular patterns we proposed are an innovative complement to the traditional classification of RCC, which might contribute to precision medicine.

ObjectiveTo analyze the prevalence, associated comorbidities, influencing factors, and identifying factors of non-obese fatty liver disease and to provide a reference for its prevention and treatment.Materials and methodsFirstly, to screen data obtained from the physical examinations of individuals conducted in the Second Affiliated Hospital of Xi’an Jiaotong University in 2021, subjects with complete data of abdominal ultrasonography, body mass index, age and sex were selected to analyze the prevalence of fatty liver disease and non-obese fatty liver disease. Secondly, to screen non-obese subjects who had data for triglycerides, fasting blood glucose, and so on, to analyze the complications, influencing factors, and identifying factors of non-obese fatty liver disease.ResultsThe prevalence of fatty liver disease was 27.8% (18,416/66,221), including 33.9% (11,921/35,131) in males and 20.9% (6,495/31,090) in females, revealing that the prevalence was significantly higher in males than in females (P < 0.001). There were 40,673 non-obese subjects screened in total, and the prevalence of non-obese fatty liver disease was 13.0% (5,307/40,673). The prevalence of non-obese fatty liver disease was 13.3% (2,208/16,572) in males and 12.9% (3,099/24,101) in females; the difference was not statistically significant (P = 0.17). The serum triglycerides level was elevated in 54.2% of subjects with non-obese fatty liver disease, and this was the most common abnormal metabolic index accompanying the disease. Logistic regression analysis showed that gender, age, body mass index, blood pressure, alanine aminotransferase, aspartate aminotransferase, fasting blood glucose, triglycerides, total cholesterol, and serum uric acid were independent risk factors for non-obese fatty liver disease (P < 0.001). For triglycerides, the area under the receiver operating characteristic curve in predicting non-obese fatty liver disease was the greatest (0.806).ConclusionThe prevalence of fatty liver disease and non-obese fatty liver disease determined by the physical examination of individuals was high, and the triglycerides is likely to be useful for the extensive screening of non-obese fatty liver disease.

Introduction: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) with renal insufficiency in recent years and the association between MAFLD and renal insufficiency is not entirely clear especially in overweight/obesity. The aim of this study was to analyze the prevalence and risk factors of MAFLD with renal insufficiency in overweight/obese adults. Methods: Individuals who attended check-up at the Second Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2021 were included. The prevalence of MAFLD with renal insufficiency [estimate glomerular filtration rate (eGFR)≤90 ml/min/1.73 m2] in overweight/obesity was estimated. Propensity score-matched (PSM) analysis, univariate and multivariate analysis were used to determine the risk factors for MAFLD with renal insufficiency. Results: From 2016 to 2021, the prevalence of MAFLD in overweight/obesity reached its highest of 44.7% in 2017 and its lowest of 36.9% in 2018；and 33.9% in 2021 and 21.8% in 2019 is the highest and lowest prevalence of MAFLD with renal insufficiency, respectively. MAFLD was more common in men, old individuals, and persons with a higher BMI, and was characterized by significant renal insufficiency. MAFLD with renal insufficiency was more common in women, old individuals, and persons with a higher BMI, and was characterized by significant metabolic dysfunction and liver fibrosis. Multivariable analysis showed BMI, uric acid and fibrosis (evaluated with non-invasive liver fibrosis score FIB-4) were independent risk factors for MAFLD with renal insufficiency. Conclusion: The prevalence of MAFLD with renal insufficiency in overweight/obese adults is quite high in the last 5 years. BMI, uric acid and fibrosis are independent risk factors for MAFLD with renal insufficiency.

Costimulatory molecules (CMGs) play essential roles in multiple cancers. However, lncRNAs regulating costimulatory molecules have not been fully explored in gastric cancer (GC). Public data of GC patients were obtained from The Cancer Genome Atlas database. R software v4.1.1, SPSS v13.0, and GraphPad Prism 8 were used to perform all the analyses. The Limma package was used for differential expression analysis. The survival package was used for patient prognosis analysis. The gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto encyclopedia of genes and genomes (KEGG) analysis were used for pathway enrichment analysis. qRT-PCR was used to detect the RNA level of target lncRNA. CCK-8 and colony formation assay were used to assess the proliferation ability of GC cells. The transwell assay was used to evaluate the invasion and migration ability of GC cells. We first identified CMG-related lncRNAs (CMLs) through co-expression analysis. Then, an eight-CML-based signature was constructed to predict patient overall survival (OS), which showed satisfactory predictive efficiency (the training cohort: 1-year AUC = 0.764, 3-year AUC = 0.810, 5-year AUC = 0.840; the validation cohort: 1-year AUC = 0.661, 3-year AUC = 0.718, 5-year AUC = 0.822). The patients in the high-risk group tend to have a worse prognosis. GSEA showed that epithelial–mesenchymal transition, KRAS signaling, and angiogenesis were aberrantly activated in high-risk patients. GO and KEGG analyses indicated that the biological difference between high- and low-risk patients was mainly enriched in the extracellular matrix. Immune infiltration analysis showed that macrophages (M1 and M2), dendritic cells, monocytes, Tregs, and T regulatory cells were positively correlated with the risk scores, partly responsible for the worsening OS of high-risk patients. Finally, lncRNA AP000695.2 was selected for further experiments. The result showed that AP000695.2 was upregulated in GC cell lines and could facilitate the proliferation, invasion, and migration of GC cells. In summary, this study established an effective prognosis model based on eight CMLs, which would be helpful for further therapy options for cancer. Also, we found that AP000695.2 could promote GC cell malignant phenotype, making it an underlying therapy target in GC.

Abstract Background Procyanidin B2 (PB2), a unique component of the grape seed and other medicinal plants. PB2 has shown wide anticancer activity in various human cancer cells. However, it remains unclear about the biological effects and associated mechanisms of PB2 on gastric cancer cells. Methods Cell proliferation was measured by CCK8 assay, and cellular lactate dehydrogenase (LDH) release was measured in the culture medium. Cellular apoptosis was observed via TUNEL staining assay and measured by caspase-3 and -9 activities. Autophagy was observed by LC3 staining. Western blot analysis was performed to verify autophagy-associated proteins (Beclin1 and Atg5) and Akt-mTOR pathway. Results PB2 reduced the viability of BGC-823 and SGC-7901 cells in a concentration-dependent manner. Furthermore, PB2 induced increased apoptosis rate of gastric cancer cells and enhanced caspase-3 and -9 activities. Simultaneously, PB2 triggered autophagy in gastric cancer cells, with enhanced LC3 staining and increased expression of Beclin1 and Atg5, while the inhibition of autophagy by 3-MA reversed the PB2-induced suppression on cell viability. In addition, PB2 significantly decreased p-Akt and p-mTOR protein expression of gastric cancer cells. Conclusion PB2 exerts anti-proliferative and apoptotic effects and induces autophagy by modulating Akt/mTOR signaling pathway. PB2 may be developed as a potential therapeutic drug for gastric cancer.

Abstract Background A series of evidence revealed that body mass index was an important confounding factor in the research of uric acid and ischemic heart disease/hypertension. The objective of this study was to investigate whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD, and the possible interactive effect of hyperuricemia and obesity. Methods We conducted a cross-sectional study in a total of 557 ultrasound diagnosed-NAFLD. The hepatic steatosis and liver fibrosis were quantitatively evaluated by transient elastography. Hyperuricemia was defined as serum uric acid > 420 μmol/L in men, > 360 μmol/L in women and obesity was defined as body mass index ≥ 25 kg/m2. The adjusted OR values of hyperuricemia and obesity were analyzed by multivariate logistic regression analysis, and the additive model was used to investigate the possible interactive effect. Results Multivariate regression analysis showed that hyperuricemia was associated with serious hepatic steatosis (1.74[1.09–2.79]) and elevated ALT (2.17[1.38–3.41]), but not with advanced fibrosis (1.61[0.91–2.85]). The association was further investigated in different BMI group. Hyperuricemia was associated with higher odds of serious hepatic steatosis (2.02[1.14–3.57]) and elevated ALT (2.27[1.37–3.76]) only in obese NAFLD, not in non-obese subjects. Similarly, patients with hyperuricemia had higher odds of advanced fibrosis in obese subjects (2.17[1.13–4.18]), not in non-obese subjects (0.60[0.14–2.70]). Furthermore, there was an additive interaction between hyperuricemia and obesity on the odds of serious hepatic steatosis (AP: 0.39[0.01–0.77]) and advanced fibrosis. (AP: 0.60[0.26–0.95]). Conclusions Hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Thus, management of uric acid may need to be targeted in obese NAFLD.

Abstract To explore the effects of urea dissociation on reducing false-positive results of the Elecsys HIV combi PT assay. A retrospective analysis was used to evaluate the false-positive rate of the Elecsys HIV combi PT assay. Six false-positive sera, six positive sera and six sera from patients with early HIV infection were collected. Dissociation was performed using 1 mol/L, 2 mol/L, 4 mol/L, 6 mol/L, or 8 mol/L urea, and HIV screening assay were then detected to select the appropriate concentration of urea dissociation. Next, 55 false-positive sera and 15 sera from early HIV infection were used to verify the best concentration of urea to achieve dissociation. Retrospective analysis showed that the COI of the Elecsys HIV combi PT assay in false-positive sera ranged from 1.0 to 200.0, and approximately 97.01%(227/234) of false-positive sera were in the range of 1.0–15.0. The avidity index (AI) in positive and false-positive sera decreased as the urea dissociation concentration increased. When the dissociation concentration was 6 mol/L, the AI of false-positive serum was between 0.0234 and 0.2567, and the AI of early HIV infection sera was between 0.4325 and 0.5017. The difference in AI between false-positive and positive samples was significant. When negativity was defined as an AI of less than 0.3970, the sensitivity and specificity were 100.0% and 100.0%, respectively. Urea-mediated dissociation could significantly reduce the false-positive rate of the Elecsys HIV combi PT assay with a low COI. Our findings provided a reference for distinguishing positive and false-positive of the Elecsys HIV combi PT assay.

Abstract Background Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further. Methods In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. Results Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4. Conclusion We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.

Background and AimsThere are few studies on non-obese fatty liver disease, the aims of this study was to analyze its prevalence, popular trends, and associated and predictive factors, so as to provide reference for its prevention and treatment.MethodsIndividuals with complete data of body mass index, sex, age, and abdominal ultrasound in Karamay Central Hospital from 2009 to 2016 were selected to analyze the prevalence and popular trends of non-obese fatty liver disease (body mass index

Abstract Background Insulin resistance (IR) and lipid peroxidation are accepted as ‘two-hit’ hypothesis of Non-alcoholic fatty liver disease (NAFLD). However, there are few published research on identifying genes which connect lipid and glucose metabolism by gene microarray. Objective To identify target genes related to lipid and glucose metabolism that might be responsible for the pathogenesis of NAFLD. Methods A rat model of NAFLD was established by feeding male rats with high-fat diet and gene expression profiles of liver tissues were determined using Agilent DNA microarray. We then investigated differentially expressed genes (DEGs) and intersection of them by using Gene Ontology (GO) and Pathway Analyses. Target genes were verified by Real-time polymerase chain reaction (RT-PCR). Results Compared with control, 932 genes, including 783 up-regulated and 149 down-regulated, exhibited differences in expression. The up-regulated genes were involved in biosynthesis, cell development, cell differentiation and down-regulated genes contributed to biological metabolic process, adipokine metabolic pathway and insulin signaling pathway. We identified genes involved in insulin signaling pathway, Notch signaling pathway and lipid synthetic process to be closely related to liver fat accumulation and insulin resistance. Among them, IGFBP7, Notch1 and HMGCR were up-regulated (2.85-fold, 3.22-fold, and 2.06-fold, respectively, all P

Background: Urinary exosomal miRNAs are gaining increasing attention for their potential as ideal non-invasive biomarkers for kidney diseases; however, little is known about their diagnostic ability for paediatric nephrotic syndrome (NS). This study explored the clinical value of urinary exosomal miRNAs for paediatric idiopathic NS. Methods: Urine samples were collected from 129 NS children and 126 age−/sex-matched healthy controls. The miRNA profile of urinary exosomes was analysed by high-throughput Illumina sequencing via synthesis (SBS) technology followed by verification with a quantitative reverse-transcription polymerase chain reaction (RT-qPCR) assay arranged in two independent cohorts. Additionally, paired urine samples from 65 of these patients were collected before and after treatment. Findings: The Illumina SBS identified 30 markedly increased urinary exosomal miRNAs in NS children compared with controls (≥ 5-fold, P 3-fold, P

The serological detection of antibodies to Treponema pallidum is essential to the diagnosis of syphilis. However, for the presence of cross-reaction, the specific antibody tests [e.g., enzyme-linked immunosorbent assay (ELISA)] always have false-positive results. In this study, we derived and validated the dissociation of urea in an attempt to alleviate the situation of false-positive antibodies to T. pallidum detected by ELISA. Six serum samples that were false-positive antibodies to T. pallidum detected by ELISA, and 16 control serum samples (8 sera positive for both specific IgG and IgM, and 8 IgG-positive and IgM-negative sera) were collected to select the appropriate dissociated concentration and time of urea. Our goal was to establish improved an ELISA method based on the original detection system of ELISA. The sensitivity of the improved ELISA was evaluated by 275 serum samples with class IgM-positive antibodies to T. pallidum. At 6 mol/L with 10 minutes dissociation of urea, 6 samples with false-positive antibodies to T. pallidum were converted to negative, and compared with true-positive antibodies to T. pallidum. The sensitivity of the improved ELISA was 100% by detecting the class IgM-positive antibodies to T. pallidum in sera of patients with syphilis. Considering the importance at the diagnosis of syphilis, antibodies to T. pallidum in serum samples should be retested by the improved ELISA method to avoid false-positive results.

Background: Endothelial progenitor cells (EPCs) derived from the bone marrow (BM) play a key role in the homeostasis of vascular repair by enhanced reendothelialization. Panax notoginseng saponins (PNS), a highly valued traditional Chinese medicine, has been shown to reduce morbidity and mortality from coronary artery disease. The present research was designed to explore the contribution of progenitor cells to the progression of atherosclerotic plaques and the possible modulatory role of PNS in this process. Methods: PNS (60 or 120 mg/kg via intraperitoneal injection) was administered over 8 weeks in apolipoprotein E knockout mice on an atherogenic diet. The sizes and histochemical alteration of atherosclerotic lesions and numbers of EPCs in BM and peripheral blood were analyzed. The expression of chemokine stromal cell-derived factor 1α (SDF-1α) and its receptor, CXCR4, was monitored as well. Results: PNS significantly reduced the lesion area and intima-to-media ratio compared to vehicle treatment. PNS also augmented endothelialization and reduced the smooth muscle cell (SMCs) content of the lesions. The number of c-kit and sca-1 double-positive progenitor cells and flk-1 and sca-1 double-positive progenitor cells were significantly increased in the BM and the peripheral blood of the PNS-treated groups. PNS treatment increased the plasma levels of SDF-1α and SCF as well as the BM levels of matrix metalloproteinase-9 (MMP-9). Moreover, the mRNA levels of SDF-1α and protein levels of CXCR4 were both increased in the BM of mice treated with PNS, while SDF-1α expression decreased. Conclusion: PNS reduce the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilization. SDF-1α-CXCR4 interactions and the possible modulatory role of PNS in this process may contribute to the increased progenitor cell mobilization.

[This corrects the article DOI: 10.1371/journal.pone.0041228.].

Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.

Pyroelectricity enables autonomous perception and remote detection in the field of infrared sensor, human machine interfacing and virtual reality. However, the low pyroelectric coefficient and inferior thermal conductivity hinders the energy conversion and signal transduction of pyroelectric sensors. Herein, we designed and prepared PZT-CNT/PVDF ternary composite (PTC) capable of infrared sensing and noncontact human machine interfacing (HMI). The incorporation of CNT not only facilitates the photo-thermal energy conversion and the heat transfer toward embedded PZT fillers, but also boost the all-trans conformation of fluoropolymer matrix and thus pyroelectric activity. The influence of CNT doping mass fractions on the pyroelectric noncontacted HMI and infrared detection properties was investigated. It is found that a doping content of 3 wt% gives rise to an optimal proximity sensitivity of 55.78 % and infrared detection optimum value of Fd 6.42 μPa−1/2, which is 13.97 % higher than that of the undoped version. This work provides insight into the interfacial coupling mechanism of pyroelectrics, and offers the new possibility for design of high-performance self-powered sensing devices.