HPC-Atlas: Computationally Constructing A Comprehensive Atlas of Human Protein Complexes.

A fundamental principle of biology is that proteins tend to form complexes to play important roles in the core functions of cells. For a complete understanding of human cellular functions, it is crucial to have a comprehensive atlas of human protein complexes. Unfortunately, we still lack such a comprehensive atlas of experimentally validated protein complexes, which prevents us from gaining a complete understanding of the compositions and functions of human protein complexes, as well as the underlying biological mechanisms. To fill this gap, we built Human Protein Complexes Atlas (HPC-Atlas), as far as we know, the most accurate and comprehensive atlas of human protein complexes available to date. We integrated two latest protein interaction networks, and developed a novel computational method to identify nearly 9000 protein complexes, including many previously uncharacterized complexes. Compared with the existing methods, our method achieved outstanding performance on both testing and independent datasets. Furthermore, with HPC-Atlas we identified 751 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected human protein complexes, and 456 multifunctional proteins that contain many potential moonlighting proteins. These results suggest that HPC-Atlas can serve as not only a computing framework to effectively identify biologically meaningful protein complexes by integrating multiple protein data sources, but also a valuable resource for exploring new biological findings. The HPC-Atlas webserver is freely available at http://www.yulpan.top/HPC-Atlas.

Understanding the Attitudes and Willingness of Adult Chinese Patients with Rheumatic Diseases Towards COVID-19 Vaccination.

Background: The SARS-CoV-2 pandemic has imposed substantial health and economic burdens on the societies. COVID-19 vaccination is the most effective method of controlling the epidemic. This study assessed the attitude, willingness, and related factors of adult patients with rheumatic diseases (RDs) in China towards COVID-19 vaccination and identified their reasons for being vaccinated. Methods:  A cross-sectional survey was administered to patients with rheumatic diseases from July 18 to August 18, 2021, using an online questionnaire. Logistic regression analysis was performed to examine the data. Results: We analyzed data drawn from 464 participants who provided valid responses. A total of 324 (69.83%) RD patients were not willing to be vaccinated, of which 76.97% believed that COVID-19 vaccination might exacerbate the diseases symptoms. Logistic regression analysis showed that a combination of experiencing systemic damage, being in the acute attack stage of the disease, and fear of the adverse impact of vaccination on rheumatism, etc., were the predominant factors affecting the intentional vaccination rate in adult patients with rheumatic diseases (p < 0.05). Conclusion: The COVID-19 intentional vaccination rate was relatively low in adult Chinese patients with RD. Public health education and the dissemination of government scientific data for patients with RD should be enhanced to increase COVID-19 vaccination rates.

Non-targeted detection of food adulteration using an ensemble machine-learning model.

Recurrent incidents of economically motivated adulteration have long-lasting and devastating effects on public health, economy, and society. With the current food authentication methods being target-oriented, the lack of an effective methodology to detect unencountered adulterants can lead to the next melamine-like outbreak. In this study, an ensemble machine-learning model that can help detect unprecedented adulteration without looking for specific substances, that is, in a non-targeted approach, is proposed. Using raw milk as an example, the proposed model achieved an accuracy and F1 score of 0.9924 and 0. 0.9913, respectively, when the same type of adulterants was presented in the training data. Cross-validation with spiked contaminants not routinely tested in the food industry and blinded from the training data provided an F1 score of 0.8657. This is the first study that demonstrates the feasibility of non-targeted detection with no a priori knowledge of the presence of certain adulterants using data from standard industrial testing as input. By uncovering discriminative profiling patterns, the ensemble machine-learning model can monitor and flag suspicious samples; this technique can potentially be extended to other food commodities and thus become an important contributor to public food safety.

Clinical study of factors associated with pregnancy outcomes in pregnant women with systemic lupus erythematosus in the southern China.

Objectives: This study aims to estimate predicted factors for maternal and fetal outcomes in Hakka pregnant women with systemic lupus erythematosus (SLE) in the southern China. Patients and methods: Between June 2014 and February 2020, we retrospectively analyzed the data of a total of 123 singleton pregnant women with SLE (mean age: 27.1±4.1 years; range, 19 to 39 years) who were referred to our rheumatology clinic. Demographic, clinical, and laboratory data of the patients were recorded. Adverse pregnancy outcomes (APOs) were assessed. Results: Multivariate logistic regression analysis revealed that preeclampsia was associated with the increased odds of APOs (odds ratios [OR]=9.538, 95% confidence interval [CI]: 2.055-44.271, p=0.004), premature birth (OR=14.289, 95% CI: 3.596-56.777, p<0.001) and low birth weight (OR=8.275, 95% CI: 2.117-32.345, p=0.002). Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody positivity was the predictor of APOs (OR=2.165, 95% CI: 1.034-4.532, p=0.040), premature birth (OR=2.849, 95% CI: 1.220-6.657, p=0.016) and pregnancy loss (OR=3.004, 95% CI: 1.086-8.305, p=0.034). The use of hydroxychloroquine and prednisone was associated with the decreased odds of APOs (OR=0.412, 95% CI: 0.198-0.860, p=0.018) and pregnancy loss (OR=0.304, 95% CI: 0.111-0.831, p=0.020). Conclusion: Our study results indicate that preeclampsia, anti-dsDNA antibody positivity, and the use of hydroxychloroquine and prednisone are independent predictors of pregnancy outcomes.

Portable and Intelligent Urine Glucose Analyzer Based on a CdTe QDs@GOx Aerogel Circular Array Sensor.

Diabetes is a public health problem characterized by hyperglycemia, high mortality, and morbidity. A simple, rapid, and sensitive glucose detection method for diabetes screening and health self-management of patients with diabetes is of great significance. Therefore, an attractive urine glucose (UG) analyzer with advantages of fastness, sensitivity, and portability was developed. A cadmium telluride quantum dots (CdTe QDs)@glucose oxidase (GOx) aerogel circular array sensor can emit visible red fluorescence when excited by a 365 nm ultraviolet light source inside the analyzer. When urine samples containing glucose were dropped onto the sensor, glucose was oxidized by GOx to produce hydrogen peroxide (H2O2), which quenched the red fluorescence of CdTe QDs. The fluorescence images of the sensor were obtained using a CCD camera, and the linear relationship between the glucose concentration and the gray value of the fluorescence image was established. The analyzer shows good sensitivity (LOD, 0.12 mM) with a wide linear range of 0.12-26 mM. Based on the linear relation, the software of the analyzer was written in the C++ language, which can automatically give the gray value of the image and the corresponding glucose concentration. The UG analyzer was used for the detection of a large number clinical samples and compared with a variety of UG test papers, which all showed good detection performance. The novel analyzer we proposed has an important significance in the screening of diabetes and the self-management of diabetic patients.

Neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios in juvenile systemic lupus erythematosus: correlation with disease manifestations.

BACKGROUND: This retrospective study aimed to investigate the usefulness of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for organ involvement and disease activity in newly diagnosed juvenile systemic lupus erythematosus (jSLE). METHODS: A total of 186 jSLE inpatients were included for analysis. All participants' clinical characteristics and laboratory data were obtained from medical records. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score scale was used to assess disease activity. Mann-Whitney U test and Kruskal-Wallis test were performed for non-parametric variables between the groups. Spearman rank correlation coefficient was used to analyze correlations between variables. RESULTS: The NLR was significantly higher in participants with serositis as compared those without serositis [2.72 (1.71-5.0) vs. 2.08 (1.42-3.15), P=0.038]. The PLR was significantly higher in participants manifesting symptoms of cutaneous rash [130.0 (92.6-235.0) vs. 112.0 (49.3-169.0), P=0.002], and arthritis [167.0 (106.0-243.0) vs. 106.0 (53.6-176.0), P<0.001], as compared to participants without such involvement. The PLR in participants with hematological involvement was significantly lower than in those without such involvement [111.0 (53.6-191.0) vs. 138.0 (107.0-185.0), P=0.016]. The PLR in participants with positive anti-Smith (anti-Sm) antibody was significantly higher than that in those with negative anti-Sm antibody [140.0 (91.6-228.0) vs. 114.0 (60.9-176.0), P=0.006]. The NLR showed positive correlations with serositis (r=0.153, P=0.037), complement C3 and C4 (r=0.152, P=0.038 and r=0.177, P=0.016, respectively). The PLR showed positive correlations with cutaneous rash (r=0.227, P=0.002), arthritis (r=0.290, P<0.001), anti-Sm antibodies (r=0.20, P=0.006) and erythrocyte sedimentation rate (ESR, r=0.159, P=0.03). Negative correlations were found between PLR and hematological involvement (r=-0.177, P=0.015). CONCLUSIONS: Both the NLR and PLR had correlations with serological indicators, and may predict organ involvement in jSLE, particularly cutaneous, arthritis, serositis, and haematological involvement.

Clinical and laboratory features, disease activity, and outcomes of juvenile systemic lupus erythematosus at diagnosis: a single-center study from southern China.

OBJECTIVES: This retrospective study aimed to analyze the clinical and laboratory features, disease activity, and outcomes of juvenile systemic lupus erythematosus (jSLE) patients from southern China. METHODS: A total of 173 jSLE patients who attended Rheumatology and Immunology Department of Meizhou People's Hospital between January 2010 and December 2019 are included for analysis. RESULTS: The mean age of disease onset was 13.65 ± 2.80 (range, 5-17). The median age at diagnosis was 13.98 ± 2.88 (range, 5-17) years. The female to male ratio was 6.5:1. Renal involvement was the most prevalent clinical feature, occurred in 71.7% of the patients. A total of 27 (15.6%) patients underwent renal biopsy, and the most common type of renal pathology was class IV (44.4%). Our study demonstrated differences in antibody clusters for which the positivity rates of anti-dsDNA antibodies and anti-Sm antibodies were higher than the other jSLE cohorts reported in China and worldwide. Cyclophosphamide combined with corticosteroids was the main treatment medication. The mean SLE Disease Activity Index (SLEDAI) score at diagnosis was 14.3 ± 7.6 (range, 3-38). Five patients died during the initial diagnosis and treatment. Infection was the major cause of death. CONCLUSION: The jSLE patients in this cohort had a higher prevalence of renal involvement, anti-dsDNA antibodies, and anti-Sm antibodies. Multicenter studies are needed to clarify the different clinical features of jSLE in southern China. KEY POINTS: • A single-center study of juvenile systemic lupus erythematosus in clinical and laboratory features. • The jSLE patients had a higher prevalence of renal involvement and antibody disorder.

The ratio of neutrophil to lymphocyte predicts interstitial lung disease and its prognosis in patients with primary Sjögren's syndrome: a retrospective analysis.

BACKGROUND: During the course of disease, some patients with primary Sjögren's syndrome (pSS) develop interstitial lung disease (ILD), which leads to a poor prognosis. There is currently a lack of methods to identify high-risk patients with ILD and predict the prognosis. The purpose of this study was to analyze the predictive value of the neutrophil to lymphocyte ratio (NLR) for the occurrence of ILD and its prognosis in patients with pSS. METHODS: According to the inclusion and exclusion criteria, patients with pSS admitted to our hospital from May 2009 to November 2020 were included. The patients were divided into either an ILD group or a non-interstitial pneumonia [non-ILD (NILD)] group. We compared the baseline data of the two groups of participants, and the participants were followed up (≥1 year) at clinic visits. Logistic multivariate regression analysis was used to analyze the risk factors related to ILD and prognosis in patients with pSS. RESULTS: A total of 217 patients with pSS were included, of which 71 (32.7%) participants were diagnosed with ILD (ILD group) at the time of pSS diagnosis, and 146 (67.3%) participants had no obvious ILD (NILD group). Based on follow-up results, logistic multivariate analysis revealed that NLR [relative risk (RR) =1.81, 95% confidence interval (CI): 1.15 to 4.73], age (RR =1.43, 95% CI: 1.06 to 3.66), non-regular treatment (RR =1.39, 95% CI: 1.03 to 3.38), ALB <35 g/L (RR =1.32, 95% CI: 1.05 to 3.17), and elevated CRP (RR =1.44, 95% CI: 1.10 to 4.53) were associated with the occurrence of ILD in participants with pSS during follow-up. Age (RR =1.28, 95% CI: 1.06 to 2.25), NLR (RR =1.43, 95% CI: 1.12 to 2.57), non-regular treatment (RR =1.51, 95% CI: 1.18 to 3.01), and ILD (RR =2.05, 95% CI: 1.36 to 4.72) were related to all-cause death during follow-up. CONCLUSIONS: The NLR is a risk factor for ILD in patients with pSS. The higher the NLR, the worse the prognosis; ILD significantly increases the risk of death in patients with pSS.

Circulating Exosomal microRNAs as Biomarkers of Systemic Lupus Erythematosus.

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=-0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=-0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

Circulating exosomal micrornas as biomarkers of systemic lupus erythematosus

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated (p<0.01), whereas miR-146a expression (p<0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 (p<0.01) and miR-155 (p<0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p<0.05) and miR-155 (R=0.33, p<0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=−0.38, p<0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=−0.39, p<0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

Clinical and immunological characteristics in 552 systemic lupus erythematosus patients in a southern province of China.

AIM: The purpose of this study was to gain a better understanding of systemic lupus erythematosus (SLE) in Hakka populations. METHODS: We studied the demographic, clinical and laboratory characteristics in a cohort of 552 SLE patients diagnosed at the Rheumatology Department in MeiZhou People's Hospital from January 2008 to December 2012. There were 495 women and 57 men (8.7 : 1) with a mean age of 35.3 years (range 12-78 years). The mean age at disease onset and the mean disease duration were 31.8 ± 14.4 years and 3.3 ± 2.8 years, respectively. RESULTS: The most common clinical manifestations were arthritis (61.6%), followed by malar rash (52.7%), photosensitivity (22.8%), mouth ulcers (17.0%) and discoid lupus (14.7%). The prevalence was 46.7% for nephritis (by biopsy), 18.3% for pleuritis, 15.6% for pericarditis and 4.9% for neuropsychiatric manifestations. The most common hematological manifestations were anemia (63.8%), followed by leucopenia (29.0%) and thrombocytopenia (14.9%). Antinuclear antibodies were detected in 99.8% of patients, followed by anti-double-stranded DNA (81.3%), anti-SSA (Sjögren's syndrome antigen A)/Ro (58.7%), anti-ribonucleoprotein (36.8%), anti-Sm (35.7%), and anti-SSB/La (15.0%). Anti-cardiolipin immunoglobulin G (IgG) and IgM were detected in 18.3% and 14.1% of patients, respectively. Active disease and infections were the two major causes of death. CONCLUSION: The clinical and immunological characteristics of the SLE patients in our study place our population in the middle of the spectrum between other Asian and Caucasian populations.