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With the development and maturation of massively parallel sequencing (MPS) technology, the mitochondrial genome (mitogenome) sequencing is increasingly applied in the forensic field. In this study, we employed the strategy of short overlapping amplicons for the whole mitogenome, library preparation with tagmentation using the Nextera® XT DNA Library Preparation Kit, sequencing on the MiSeq FGxTM Forensic Genomics System and analyzing data using the mitochondrial(mtDNA) MSR Plug-in and the mtDNA Variant Analyzer. A total of 27 libraries and 56 libraries were sequenced in a run using MiSeq Reagent Kit v2 and v3, respectively. Results showed more than 1800 × of averaged depth of coverage (DoC) at each position. Concordant haplotypes of 9947 A and 2800 M were obtained at 32 variants. Cross-reactivity was observed with 1 ng primate DNA and 10 ng non-primate DNA but could be easily distinguished. Full and accurate variants were obtained from at least 50 pg input DNA and from minor contributors between 19:1 and 1:19 mixed ratios with known reference profiles. More than 86% variants were detected from ≥200-bp degraded samples but its haplotype was assigned to more ancestral haplogroup. Further, a total of 3 962 variants were observed at 613 nucleotide positions from 103 Xibe mitogenomes with 25:1 ratio of transitions to transversions. Two new transversions (C13735A and A14755C) and two tri-alleles at nps 9824 and 16092 were identified. There were 103 unique mitogenome haplotypes from 103 Chinese Xibe that were assigned to 79 haplogroups. Haplogroup D was the preponderant top-level haplogroup in Xibe followed by F, B, M, A, N, G, C, Z, Y, HV and J. Random match probability (RMP) and haplotype diversity (HD) of the whole mitogenome was calculated as 0.0097 and 1.0000, respectively. Compared with HVS-I only, RMP decreased 33.56%, while the number of haplotypes and HD increased 15.73% and 0.49%, respectively. Principal component analysis (PCA) showed that Xibe was clustered to East and Southeast Asian. As a whole, this MPS strategy is suitable for the whole mitogenome sequencing especially for degraded samples and can facilitate generating mitogenome data to support the routine application in forensic sciences. EMP00726 is the first whole mitogenome dataset from Xibe contributed to the EMPOP. Supplemental data for this article are available online at. [ABSTRACT FROM AUTHOR] more...

Objectives: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy.Methods: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets.Results: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells.Conclusions: Low-dose IL-2 might be effective and tolerated in treatment of SLE.Trial Registration Number: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137). [ABSTRACT FROM AUTHOR] more...

Using 2,3-diaminopyridine and citric acid as precursors, blue fluorescent nitrogen-doped carbon quantum dots (NCQDs) with a narrow size distribution (∼7.2 nm) were prepared and applied in the following assay for mercury ion detection at a weight ratio of 2,3-diaminopyridine:citric acid = 1:1 (0.2 g: 0.2 g, 20 mL for H 2 O), 220 °C, and 10 h. NCQDs was characterized by TEM, FT-IR, XPS, UV–Vis and EDS, and the prepared NCQDs display excitation-independent behavior due to less surface defects and uniform size. The optimal excitation and emission wavelengths of the NCQDs were 380 nm and 430 nm, respectively. Interestingly, the fluorescence of the NCQDs could be rapidly and selectively quenched by Hg2+ within 9 min at room temperature without further modification. Under optimal conditions, the limit of detection (LOD) was measured to be at the nanomolar level (42.4 nmol/L) with a linear range of 0–5.0 μmol/L, and fluorescence analysis of NCQDs was successfully used for the qualitative and quantitative analysis of mercury ions in food samples. Furthermore, our results revealed that fluorescence quenching occurred under the common fluences of the inner filter effect, and the static quenching effect was authenticated in the process in which Hg2+ coordinates with the NCQDs to form nonfluorescent complexes. • The NCQDs was applied to the detection of mercury ions. • The NCQDs was characterized by TEM, FT-IR, XPS, UV–Vis and PL. • The detection limit is ∼42.4 nmol/L. • The NCQDs was successfully detected to Hg2+ in food samples. [ABSTRACT FROM AUTHOR] more...

Objective: To stratify systemic lupus erythematosus (SLE) patients clinically, to analyze the clinical characteristics of patients with and without disease activity, and to explore the application va-lue of key clinical indicators in assessing disease activity, as well as to construct an evaluation model., Methods: A retrospective analysis was conducted on clinical data of the SLE patients diagnosed at Peking University People' s Hospital from May 1995 to April 2014. Demographic information, clinical manifestations, laboratory tests, and antibody detection results were collected. The patients were divided into active and inactive groups based on systemic lupus erythematosus disease activity index 2000(SLEDAI-2000)scores. t -tests, Mann-Whitney U tests, and χ 2 tests were used to compare the differences between the groups. Spearman correlation analysis was used to evaluate the relevant clinical indicators associated with SLE activity in the active disease group. Based on the results of statistical analysis, a Logistic regression model was constructed, and the performance of the model was evaluated., Results: No significant differences were found in demographic characteristics between the two groups. In the active disease group, positive rates of antinuclear antibodies (ANA) and anti-double-stranded DNA antibodies (anti-dsDNA) were increased; white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), lymphocytes (LY), total protein (TP), albumin (ALB), and complement 3(C3) levels were significantly decreased; while immunoglobulin A and G levels were markedly elevated. The correlation analysis results showed that hemoglobin, albumin, C3, and complement 4(C4) had higher correlation indices compared with other clinical indicators. Among these, C3 exhibited a certain negative correlation with disease activity. The Logistic regression model based on 12 significantly different indicators ( P < 0.05) achieved an accuracy of 91.4%, sensitivity of 94.4%, specificity of 81.0%, and the area under curve (AUC) of the receiver operating characteristic (ROC) was 0.944., Conclusion: This study comprehensively evaluated a range of clinical indicators related to SLE disease activity, providing a thorough understanding of both laboratory and clinical markers. The Logistic regression model, which was primarily constructed using laboratory test indicators, such as inflammatory markers, immune response parameters, and organ involvement metrics, demonstrated a high degree of accuracy in assessing the disease activity in SLE patients. Consequently, this model might provide a new basis for the diagnosis and treatment of SLE patients, offering significant clinical diagnostic value. more...

Objectives: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy., Methods: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets., Results: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells., Conclusions: Low-dose IL-2 might be effective and tolerated in treatment of SLE., Trial Registration Number: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...

Objectives: This study was performed to evaluate the performance and clinical significance of lipopolysaccharide-binding protein (LBP) as a disease activity biomarker in rheumatoid arthritis (RA)., Methods: LBP levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations between LBP and the clinical and serological features of RA and its clinical significance as a RA disease activity biomarker were analysed., Results: The serum level of LBP in RA was significantly elevated compared to those in OA, SLE, pSS and HC. The level of LBP in RA synovial fluid (SF) was higher than that in OA SF. LBP was significantly correlated with RA disease activity parameters such as ESR, CRP, tender joint counts, swelling joint counts and DAS28. Furthermore, LBP positive RA patients were more likely to show higher disease activity (DAS28>5.1), positive APF, interstitial lung disease and metabolic disorders. The predictive value of LBP on high disease activity was comparable with those of CRP and ESR. In 52.5% of the patients with active disease but negative in CRP /ESR, LBP was still positive and correlated with swelling joint counts., Conclusions: LBP is a sensitive serum biomarker to evaluate RA disease activity, and it could be a promising laboratory marker to assist RA disease activity assessment in active RA patients with negative ESR or CRP. more...

Objective: To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta1 * 0401, * 0402, * 0403, * 0404 and * 0101 subtypes on the protein kinase A (PKA) signaling pathway., Methods: Adenylate cyclase (AC), cAMP and PKA activity in transfectants expressing RA-associated HLA-DRbeta1 subtypes and their mutants were detected., Results: Compared to HLA-DRbeta1 * 0402 transfectants, the RA-associated HLA-DRbeta1 * 0401, * 0404 and * 0101 transfectants produced significantly lower levels of AC, cAMP and PKA., Conclusion: RA-associated HLA-DRbeta1 molecules are involved in the pathogenesis of RA through down-regulation of the PKA signaling pathway. more...