NLRP12 is an innate immune checkpoint for repressing IFN signatures and attenuating lupus nephritis progression.

Signaling driven by nucleic acid sensors participates in interferonopathy-mediated autoimmune diseases. NLRP12, a pyrin-containing NLR protein, is a negative regulator of innate immune activation and type I interferon (IFN-I) production. Peripheral blood mononuclear cells (PBMCs) derived from systemic lupus erythematosus (SLE) patients expressed lower levels of NLRP12, with an inverse correlation with IFNA expression and high disease activity. NLRP12 expression was transcriptionally suppressed by runt-related transcription factor 1-dependent (RUNX1-dependent) epigenetic regulation under IFN-I treatment, which enhanced a negative feedback loop between low NLRP12 expression and IFN-I production. Reduced NLRP12 protein levels in SLE monocytes was linked to spontaneous activation of innate immune signaling and hyperresponsiveness to nucleic acid stimulations. Pristane-treated Nlrp12-/- mice exhibited augmented inflammation and immune responses; and substantial lymphoid hypertrophy was characterized in NLRP12-deficient lupus-prone mice. NLRP12 deficiency mediated the increase of autoantibody production, intensive glomerular IgG deposition, monocyte recruitment, and the deterioration of kidney function. These were bound in an IFN-I signature-dependent manner in the mouse models. Collectively, we reveal a remarkable link between low NLRP12 expression and lupus progression, which suggests the impact of NLRP12 on homeostasis and immune resilience.

LCMD: Lung Cancer Metabolome Database.

Lung cancer, one of the most common causes of cancer-related death worldwide, has been associated with high treatment cost and imposed great burdens. The 5-year postoperative survival rate of lung cancer (13%) is lower than many other leading cancers indicating the urgent needs to dissect its pathogenic mechanisms and discover specific biomarkers. Although several proteins have been proposed to be potential candidates for the diagnosis of lung cancer, they present low accuracy in clinical settings. Metabolomics has thus emerged as a very promising tool for biomarker discovery. To date, many lung cancer-related metabolites have been highlighted in the literature but no database is available for scientists to retrieve this information. Herein, we construct and introduce the first Lung Cancer Metabolome Database (LCMD), a freely available online database depositing 2013 lung cancer-related metabolites identified from 65 mass spectrometry-based lung cancer metabolomics studies. Researchers are able to explore LCMD via two ways. Firstly, by applying various filters in the "Browse Metabolites" mode, users can access a list of lung cancer-related metabolites that satisfy the filter specifications. For each metabolite, users can acquire the value of the fold change (cancer/normal), statistical significance (p-value) of the fold change, and the comparative research designs of all the mass spectrometry-based lung cancer metabolomics studies that identify this metabolite. Secondly, by applying various filters in the "Browse Studies" mode, users can obtain a list of mass spectrometry-based lung cancer metabolomics studies that satisfy the filter specifications. For each study, users can view the type of studied specimen, mass spectrometry (MS) method, MS data processing software, and differential analysis method, as well as all the identified lung cancer-related metabolites. Furthermore, the overview of each study is clearly illustrated by a graphical summary. The LCMD (http://cosbi7.ee.ncku.edu.tw/LCMD/) is the first database that brings together the meaningful information of lung cancer-related metabolites. The development of the LCMD is envisioned to promote the biomarker discovery of lung cancer.

An Augmented Reality (AR) App Enhances the Pulmonary Function and Potency/Feasibility of Perioperative Rehabilitation in Patients Undergoing Orthopedic Surgery.

Perioperative rehabilitation is crucial for patients receiving surgery in order to reduce complications and mortality. Conventional methods such as verbal instructions and pre-recorded video are commonly used, but several disadvantages exist. Therefore, we developed an augmented reality (AR) app that includes respiration training, resistance muscle training, and walking training for surgery preparation. The aim of this pilot study was to compare the effects of AR-based training rehabilitation programs with conventional (non-AR-based) programs considering the objective pulmonary function and subjective feasibility and potency in orthopedic patients. This prospective study was conducted in a medical center in Taiwan between 2018 to 2021. Sixty-six patients undergoing elective orthopedic surgery were allocated with a 1:1 ratio to non-AR or AR groups according to their wishes. After training, the inspiratory flow rate of the AR group was higher than that of the non-AR group pre-operatively. As for the subjective assessment, the feasibility (level of confidence and anxiety reduction) and potency (cooperation and educative effect) were superior in AR-based training, compared with the conventional training model. Our study showed that patients using our AR app had better subjective and objective outcomes compared with a conventional model for perioperative rehabilitation.

Association between Traditional Chinese medicine and a lower risk of dementia in patients with major depression: A case-control study.

ETHNOPHARMACOLOGICAL RELEVANCE: Major depression is an important risk factor for dementia. Traditional Chinese medicine (TCM) can alleviate the symptoms of major depression. However, it is unclear whether TCM decreases the risk of dementia in patients with major depression. Therefore, in this nationwide case-control study, we aimed to evaluate the association between TCM and the risk of dementia. MATERIALS AND METHODS: We included 31,981 major depression patients with dementia from the National Dementia Database as the case group, and 4391 major depression patients without dementia from a one-million random sample database as the control group. We matched age (plus or minus two years), sex, and year of depression diagnosis based on a 1:4 ratio. RESULT: There were 11,724 and 2931 patients in the case and control groups, respectively. Based on a conditional logistic regression analysis, the TCM groups exhibited significantly lower odds ratios with a 95% confidence interval of 0.83 (0.74-0.91). TCM treatment for more than 90 days, dispersing Qi, and activating blood circulation resulted in lower dementia risk with the following odds ratios and 95% confidence intervals: 0.60 (0.56-0.68), 0.87 (0.74-1.08), and 0.66 (0.49-0.81). CONCLUSION: The results suggest that TCM is associated with lower dementia risk in major depression patients.

Extraction strategies for tackling complete hair metabolome using LC-HRMS-based analysis.

Over recent years, metabolomics has been featured as the state-of-the-art technology that successfully opens the paths to understanding biological mechanisms and facilitating biomarker discovery. However, the inherent dynamic and sensitive nature of the metabolome have been challenging the accuracy of capturing the timepoints of interest while using biofluids such as urine and blood. Hair has thus emerged as a valuable analytical specimen for the long-term and retrospective determinations. Unfortunately, notwithstanding the apparent interest on global hair metabolomics, very few studies have engaged in the optimisation of the extraction strategy. In this study, we systemically investigated the extraction procedures for hair metabolome using a single factor experimental design. Three pH values (acidic, neutral, and basic) in aqueous solution, six extraction solvents (methanol, acetonitrile, acetone, phosphate-buffered saline, deionised water, and dichloromethane), different compositions of selected solvent mixtures and their sequential extraction, and a series of extraction times (15, 45, 60, 120, 240, and 480 min) were evaluated. The ideal condition for hair extraction is ultrasonic-assisted extraction with methanol:phosphate-buffered saline 50:50 (v/v) under +55 °C for 240 min. This strategy may secure the true composition of the metabolome, maximise the signal abundance, and guarantee a high coverage of wide-range metabolites in a straightforward approach. The optimised extraction strategy was then coupled with structure annotation tools for hair metabolome profiling. After a single RPLC-HRMS run, hair metabolite identification was achieved as the annotations of 171 probable structures and 853 tentative structures as well as the assignments of 414 unequivocal molecular formulae. In conclusion, we established an efficient extraction strategy for untargeted hair metabolomics, which the method is deliverable to any analytical laboratories and the sample can be directly profiled by means of a conventional RPLC-HRMS gradient.

Incidence of Cellulitis Following Acupuncture Treatments in Taiwan.

Background: Cellulitis is a complication of acupuncture, but the risk factors and annualized incidence remain unclear. Objective: This study analyzed the incidence and risk factors of cellulitis related to acupuncture in a cohort of one million participants derived from Taiwan's Longitudinal Health Insurance Database. Methods: We tracked this cohort between 1997 and 2012 and recorded all outpatient medical information including diagnosis and treatment. Patients were categorized according to age, gender, comorbidities, residential area, and number of acupuncture treatments. We compared the incidence and risk of cellulitis between different demographics and comorbidities by logistic regression analysis and adjusted odds ratio (aOR) with a 95% confidence interval (95% CI). Results: We included 407,802 patients and 6,207,378 acupuncture treatments. The incidence of cellulitis after acupuncture was 64.4 per 100,000 courses of acupuncture treatment. The most common sites of cellulitis after acupuncture were the legs, feet, and face. Comorbidity was associated with post-acupuncture cellulitis; a multivariate logistic regression analysis showed that chronic kidney disease (aOR, 1.71; 95% CI, 1.55-1.88), rheumatoid arthritis (aOR, 1.86; 95% CI, 1.21-3.60), liver cirrhosis (aOR, 1.23; 95% CI, 1.15-1.32), diabetes mellitus (aOR, 1.69; 95% CI, 1.57-1.82), stroke (aOR, 1.44; 95% CI, 1.31-1.58), varicose veins (aOR, 2.38; 95% CI, 2.17-2.84), or heart failure (aOR, 1.81; 95% CI, 1.65-1.98) significantly increased cellulitis. Repeated exposure to acupuncture treatment was associated with an increased risk of cellulitis. Conclusions: A variety of chronic diseases may increase the risk of cellulitis after acupuncture. Physicians asked about past medical history before acupuncture might help to reduce cellulitis.