Diagnostic delay and its associated factors in Chinese axial spondyloarthritis: A single-center study of 1295 patients.

AIM: To delineate the landscape of diagnostic delay in Chinese axial spondyloarthritis (axSpA), investigate its associated factors, and explore its potential impact on medication modalities. METHODS: A total of 1295 patients fulfilling the ASAS classification criteria were obtained. Demographic and clinical data were collected through face-to-face interviews, based on predesigned questionnaires and available medical records. Logistic regression analyses under univariate and multivariable model were performed, using the median of diagnostic delay as the cut-off point for group classification. Differences between early- and late-diagnosed groups were subsequently compared by the Pearson chi-square test or Mann-Whitney U test. RESULTS: Of 1295 axSpA patients, 80.3% were male and the median of disease duration was 8.0 years. The median (IQR) diagnostic delay in Chinese axSpA was 3.0 (1.0 ~ 7.0) years and 24.8% of them reported a history of misdiagnosis. Older age at onset (OR = 0.97, p < .001) and higher education attainment (p = .001) were correlated with early diagnosis of axSpA, whereas coming from less developed areas (p = .002), a history of peripheral arthritis at the time of diagnosis (OR = 1.58, p = .002) and history of misdiagnosis (OR = 1.98, p < .001) increased the risk of diagnostic delay. Oral medication modalities were similar between two groups, but the proportion with no medication ever was higher in the late-diagnosed group (26.5% vs. 20.7%, p = .02). CONCLUSION: Our findings depicted a detailed spectrum of diagnostic delay in Chinese axSpA, verified five associated factors that may help facilitate timely diagnosis of axSpA, and pinpointed that timely medication was unsatisfying, especially in the late diagnosis group.

Preclinical evaluation of the safety and effectiveness of a new bioartificial cornea.

Cross-linking agents are frequently used to restore corneal properties after decellularization, and it is especially important to select an appropriate method to avoid excessive cross-linking. In addition, how to promote wound healing and how to improve scar formation require further investigation. To ensure the safety and efficacy of animal-derived products, we designed bioartificial corneas (BACs) according to the criteria for Class III medical devices. Our BACs do not require cross-linking agents and increase mechanical strength via self-cross-linking of aldehyde-modified hyaluronic acid (AHA) and carboxymethyl chitosan (CMC) on the surface of decellularized porcine corneas (DPCs). The results showed that the BACs had good biocompatibility and transparency, and the modification enhanced their antibacterial and anti-inflammatory properties in vitro. Preclinical animal studies showed that the BACs can rapidly regenerate the epithelium and restore vision within a month. After 3 months, the BACs were gradually filled with epithelial, stromal, and neuronal cells, and after 6 months, their transparency and histology were almost normal. In addition, side effects such as corneal neovascularization, conjunctival hyperemia, and ciliary body hyperemia rarely occur in vivo. Therefore, these BACs show promise for clinical application for the treatment of infectious corneal ulcers and as a temporary covering for corneal perforations to achieve the more time.

Long-Lived Photoacid-Doped Conducting Composites Induce Photocurrent for Efficient Wound Healing.

Electrical stimulation is an effective strategy for facilitating wound healing. However, it is hindered by unwieldy electrical systems. In this study, a light-powered dressing based on long-lived photoacid generator (PAG)-doped polyaniline composites is used, which can generate a photocurrent under visible light irradiation to interact with the endogenous electric field and facilitate skin growth. Light-controlled proton binding and dissociation result in oxidation and reduction of the polyaniline backbone, inducing charge transfer to generate a photocurrent. Due to the rapid intramolecular photoreaction of PAG, a long-lived proton-induced localized acidic environment is formed, which protects the wound from microbial infection. In summary, a simple and effective therapeutic strategy is introduced for light-powered and biocompatible wound dressings that show great potential for wound treatment.

Biomimetic Antithrombotic Tissue-Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Herein, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen-gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming "harmful" substances into "beneficial" factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.

Overexpressed RAD51 promoted osteogenic differentiation by activating IGF1R/PI3K/AKT pathway in osteoblasts.

BACKGROUND: Osteoporosis (OP) is a skeleton disease induced by imbalance between osteoblast and osteoclast. Osteogenic differentiation of osteoblasts is of great importance, and the regulatory mechanisms are urgent to be studied. METHODS: Differentially expressed genes were screened from microarray profile related to OP patients. The dexamethasone (Dex) was used to induce osteogenic differentiation of MC3T3-E1 cells. MC3T3-E1 cells were exposed to microgravity environment to mimic OP model cells. Alizarin Red staining and alkaline phosphatase (ALP) staining were used to evaluate the role of RAD51 in osteogenic differentiation of OP model cells. Furthermore, qRT-PCR and western blot were applied to determine expression levels of genes and proteins. RESULTS: RAD51 expression was suppressed in OP patients and model cells. Alizarin Red staining and ALP staining intensity, the expression of osteogenesis-related proteins including runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and collagen type I alpha1 (COL1A1) were increased by over-expressed RAD51. Furthermore, RAD51 related genes were enriched in IGF1 pathway, and up-regulated RAD51 activated IGF1 pathway. The effects of oe-RAD51 on osteogenic differentiation and IGF1 pathway were attenuated by IGF1R inhibitor BMS754807. CONCLUSIONS: Overexpressed RAD51 promoted osteogenic differentiation by activating IGF1R/PI3K/AKT signaling pathway in OP. RAD51 could be a potential therapeutic marker for OP.

Gelation of highly entangled hydrophobic macromolecular fluid for ultrastrong underwater in situ fast tissue adhesion.

Although strong underwater bioadhesion is important for many biomedical applications, designing adhesives to perform in the presence of body fluids proves to be a challenge. To address this, we propose an underwater and in situ applicable hydrophobic adhesive (UIHA) composed of polydimethylsiloxane, entangled macromolecular silicone fluid, and a reactive silane. The hydrophobic fluid displaced the boundary water, formed an in situ gel, bonded to tissues, and achieved exceptional underwater adhesion strength. Its underwater lap shear adhesion on porcine skin was significantly higher than that of cyanoacrylate and fibrin glues, demonstrating excellent water resistance. The burst pressure of UIHA on porcine skin was 10 times higher than that of fibrin glue. The cytocompatible UIHA successfully sealed ruptured arteries, skin, and lungs in rats, pigs, rabbits, and dogs. Together, the gelation of highly entangled hydrophobic macromolecular fluid provided a means to prepare underwater bioadhesives with strong bonding to tissues and excellent water resistance.

Ataxia-televangelist mutated (ATM)/ ATR serine/threonine kinase (ATR)-mediated RAD51 recombinase (RAD51) promotes osteogenic differentiation and inhibits osteoclastogenesis in osteoporosis.

Osteoporosis is a metabolic bone disease that significantly affects the quality of life and can even lead to death. In this study, we aimed to investigate the role of RAD51 recombinase (RAD51) in osteoblast and osteoclast differentiation. We analyzed differentially expressed genes using microarray analysis. The osteogenic differentiation capability was analyzed by alkaline phosphatase (ALP) staining and alizarin red staining assays. Osteogenesis and osteoclast related genes expression was detected using quantitative real-time PCR (qPCR) and Western blotting. The phosphorylation of Ataxia-telangiectasia mutated (ATM) and ATR serine/threonine kinase (ATR) was tested using Western blotting. The effect of RAD51 on osteoporosis was also explored in vivo. The results showed that RAD51 was downregulated in osteoporosis, but upregulated in differentiated osteoblasts. Overexpression of RAD51 enhanced the differentiation of osteoblasts and suppressed the formation of osteoclasts. Furthermore, p-ATM and p-ATR levels were upregulated in osteoblasts and downregulated in osteoclasts. RAD51 expression was reduced by the ATM/ATR pathway inhibitor AZ20. AZ20 treatment inhibited osteoblastogenesis and promoted osteoclastogenesis, whereas RAD51 reversed the effects induced by AZ20. Moreover, RAD51 improved bone microarchitecture in vivo. Taken together, ATM/ATR signaling-mediated RAD51 promoted osteogenic differentiation and suppressed osteoclastogenesis. These findings reveal a critical role for RAD51 in osteoporosis.

Programmable dual responsive system reconstructing nerve interaction with small-diameter tissue-engineered vascular grafts and inhibiting intimal hyperplasia in diabetes.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) with hyperglycemia resistance have not been constructed. The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs. Here, inspired by bionic regulation of nerve on vascular, we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells (VSMCs). The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs. To address this concern, sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels. An external primary Reactive Oxygen Species (ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia. Then, the internal secondary ATP-responsive DENND1A (guanine nucleotide exchange factor) system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes. The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation. At day 90, the abnormal VSMCs phenotype was not detected in the sdTEVGs, which maintained long-time patency without intima hyperplasia. Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.

Dynamics of Adaptive Immune Cell and NK Cell Subsets in Patients With Ankylosing Spondylitis After IL-17A Inhibition by Secukinumab.

Background: Anti-IL-17A therapy is generally effectively applied in patients with Ankylosing Spondylitis (AS) to achieve and maintain remission. However, the influence of anti-IL-17A on the composition of the immune system is not apparent. Our prospective study was to explore the changes in immune imbalance regarding T cell, B cell and natural killer (NK) cell subsets after secukinumab treatment in AS patients. Methods: Immune cell distribution of 43 AS patients treated with secukinumab for 12 weeks and 47 healthy controls (HC) were evaluated. Flow cytometry using monoclonal antibodies against 25 surface markers was accomplished to explore the frequencies of lineage subsets. The differences between HC, AS pre-treatment, and post-treatment were compared using the paired Wilcoxon test, Mann-Whitney U test, and ANOVA. Results: AS patients had altered immune cell distribution regarding T cell and B cell subsets. Apart from activated differentiation of CD4+ T cell, CD8+ T cell and B cell, higher levels of cytotoxic T (Tc) two cells and Tc17 cells were noted in AS patients. We confirmed that helper T (Th) one cell became decreased; however, Th17 cells and T follicular helper (Tfh) 17 cells went increased in AS. After 12 weeks of secukinumab therapy, CRP and ASDAS became significantly decreased, and meanwhile, the proportions of Th1 cells, Tfh17 cells and classic switched B cells were changed towards those of HC. A decreased CRP was positively correlated with a decrease in the frequency of naïve CD8+ T cells (p = 0.039) and B cells (p = 0.007) after secukinumab treatment. An elevated level of T cells at baseline was detected in patients who had a good response to secukinumab (p = 0.005). Conclusion: Our study confirmed that AS patients had significant multiple immune cell dysregulation. Anti-IL-17A therapy (Secukinumab) could reverse partial immune cell imbalance.

Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart.

Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI.

Comorbidities and factors influencing frequent gout attacks in patients with gout: a cross-sectional study.

OBJECTIVES: The objective was to identify the comorbidities of gout, to compare gender difference and independent factors of frequent gout attacks (> 20 times). METHOD: Demographic, clinical variables, self-reported comorbidities, and biochemical variables (i.e., initial serum uric acid (UA) and UA at visit) were collected in this cross-sectional study. Gout attack times were recorded as ≤ 5, 6-10, 11-20, and > 20. Adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to explore the association between selected risk factors and frequent gout attacks. RESULTS: Six hundred fifty-three gout patients with a mean age of 48.3 ± 15.8 years were included, 84.7% of whom were males. The median gout duration was 6.0 (3.0-12.0) years. The most common comorbidities involved hypertension (166, 25.4%), coronary artery disease (CAD) (67, 10.3%), chronic kidney disease (66, 10.1%), and hyperlipidemia (57, 8.7%). Abnormalities including nephrolithiasis (29.4%), hydronephrosis (3.2%), and gallstones (11.9%) were also found. Although female patients had a longer disease duration and more CAD, they had a lower level of UA, creatine, and C-reactive protein (CRP) but higher high-density lipoprotein cholesterol (HDL-C) (p < 0.05). A positive correlation between UA and triglycerides was found in females (p = 0.039). Patients with renal insufficiency or nephrolithiasis had longer disease duration and more gout attacks (p < 0.001). In multivariable regression analysis, only gout duration (OR = 7.89, p < 0.001) and UA (OR = 1.48, p < 0.001) was independent factors of frequent gout attacks. CONCLUSIONS: Comorbidity screening involving dyslipidemia is often neglected in gout patients. Gout duration and UA are the risk factors of frequent gout attacks. Key Points • Comorbidities can be overlooked if the screening for lipid levels, cardiovascular disease, and kidney disease is not completed. • There are differences in comorbidities and biochemical findings between male and female patients with gout. • Gout duration and serum uric acid level are independent risk factors of frequent gout attacks.

TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis.

BACKGROUND: Studies into ankylosing spondylitis (AS) and its relationship with immune imbalance are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune imbalance is unclear. METHODS: A total of 40 immune cells were tested with flow cytometry, and the results of 105 healthy control (HC) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed. RESULTS: Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (P < 0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (P < 0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (P < 0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (P < 0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (P < 0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (P < 0.001, 0.0001, and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (P < 0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (P < 0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of naïve CD4+ T cells had decreased (P < 0.05) but Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (P < 0.01 and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in C-reactive protein (CRP) (r = 0.489, P = 0.018). CONCLUSIONS: We found that active-stage AS patients have an immunity imbalance of frequency involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. TNF-α inhibitor Anbainuo can not only help to inhibit disease activity but can also improve the immune imbalance of CD4+ T cells and negative regulatory cells in frequency. But CD8+ T cells have not been rescued.

Circulating Retinol-Binding Protein 4 as a Possible Biomarker of Treatment Response for Ankylosing Spondylitis: An Array-Based Comparative Study.

OBJECTIVE: To explore proteins associated with ankylosing spondylitis (AS) and to investigate potential proteins that may predict treatment response of adalimumab (ADA) in AS patients. METHODS: In the discovery cohort, 39 AS patients and 20 healthy controls (HCs) were included, and 16 AS patients received ADA treatment for 24 weeks after included. In the validation cohort, 43 AS patients and 39 HCs were enrolled, and all 43 patients received ADA treatment after enrollment. Blood samples and clinical information were collected from two cohorts at baseline from all participants and week 24 from patients received ADA treatment. A human antibody array containing 1,000 proteins was used in the discovery phase, and Elisa kits were used for protein validation. RESULTS: Compared with HCs, we identified 53 differentially expressed proteins (DEPs) in AS patients. Bioinformatics analysis revealed they were mostly enriched in coagulation function-related pathways, acute response signaling, and LXR/RXR activation. Bone metabolism pathways were also associated. Comparison between samples of pre- and post-ADA treatment revealed 42 DEPs. They were mostly associated with bone metabolism and inflammation response pathways. Significant enrichment was also found in LXR/RXR activation but not the coagulation function-related pathways. Upstream regulator analysis suggested that most regulators also significantly functioned under usage of ADA. Precisely, seven proteins were abnormally expressed in AS and restored after ADA treatment. Retinol-binding protein 4 (RBP4), one of the seven proteins, was validated that its baseline levels were inversely correlated with improvements in Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Likewise, percentage changes in RBP4 levels were inversely correlated with changes in ASDAS-CRP score. CONCLUSION: A dysregulated serum protein profile existed in AS. ADA exerted a considerable but not entire alteration toward the dysregulation. RBP4 could be a biomarker for predicting and monitoring ADA treatment response.

Investigation and analysis of HEp 2 indirect immunofluorescence titers and patterns in various liver diseases.

INTRODUCTION: Antinuclear antibody (ANA) testing using indirect immunofluorescence assay (IIFA) is a common and economical method which contributes to detect systemic autoimmune diseases (SARD) and autoimmune liver diseases (AILD). The primary aim of our study was to investigate ANA positivity and their patterns in multiple liver diseases, including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), hepatitis B virus infection (HBV), hepatitis C virus infection (HCV), and hepatic carcinoma (HCC). Besides, we also compared the ANA titers and patterns in patients with liver disease, SARD, and healthy controls (HC). METHODS: A total of 2537 patients with SARD, 137 PBC cases, 57 AIH cases, 3420 HBV cases, 769 HCV cases, 268 HCC cases, and 1073 HC were retrospectively assessed. The titers and patterns of ANA were detected with the IIFA method. RESULTS: ANA positivity rate was considerably discernible between these diseases, which is 90.1% in SARD, 93.4% in PBC, 49.1% in AIH, 19.1% in HBV, 13.9% in HCV, and 23.5% in HCC. Moreover, only 4.9% of HCC cases, 2.5% of HBV patients, and 1.6% of HCV patients had an ANA titer ≥ 1:320. The mixed pattern which composed of at least two patterns majorly lied in PBC. AC-15 and AC-21 was frequently related to liver diseases; the former pattern was more frequently found in AIH (84.2%) and PBC (8.8%), and the latter pattern was easily seen in PBC (62.2%) and HCC (22.6%). The positive rate of ANA in HC was 12.2%, and its major pattern was AC-2. CONCLUSIONS: There are differences in ANA positivity among patients with SARD and various liver diseases. Some mixed patterns may provide important evidence for the diagnosis of PBC. Clinicians should pay attention to ANA patterns and titer during the interpretation of this test. Key Points • Defining the clinical relevance of antinuclear antibody (ANA) using indirect immunofluorescence assay in the context of diseases can be an important tool for the clinician in the diagnostic work-up of patients with liver diseases. • The mixed pattern of ANA is majorly found in primary biliary cirrhosis (PBC). ANA patterns including AC-15 and AC-21 are frequently related to liver diseases. AC-15 is more often found in autoimmune hepatitis (AIH) (84.2%) and PBC (8.8%), and AC-21 is easily found in PBC (62.2%, and hepatic carcinoma (HCC) (22.6%). • ANA positivity can be seen in 19.1% of hepatitis B virus infection (HBV) cases, 13.9% of hepatitis C virus infection (HCV) cases, and 23.5% of HCC cases. Only 2.5% of HBV patients, 1.6% of HCV patients, and 4.9% of HCC cases have an ANA titer ≥ 1:320.

Analysis of 47 Non-MHC Ankylosing Spondylitis Susceptibility Loci Regarding Associated Variants across Whites and Han Chinese.

OBJECTIVE: To present a systematic evaluation of 47 non-MHC ankylosing spondylitis (AS) susceptibility loci that have been initially discovered through white genome-wide association studies in Han Chinese. METHODS: Originally, 10,743 samples representing north and south Chinese in 4 datasets were obtained. After data quality control and imputation, metaanalysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNP) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages of AS-associated variants were compared. Functional annotations of AS-associated variants were conducted using HaploReg, RegulomeDB, and rVarBase databases. RESULTS: We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (p = 6.30 × 10-10), rs10050860 (p = 4.09 × 10-5) and rs8070463 (p = 1.03 × 10-4). Potential susceptible SNP within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15), and rs62074054 (17q21). Epistatic interactions between 3 ERAP1 SNP (rs17401719, rs30187, and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect, while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than in whites. Further genomic annotation pinpointed 35 candidate functional SNP, especially in the 2p15, ERAP1, and NPEPPS-TBKBP1 regions. CONCLUSION: Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1, and NPEPPS-TBKBP1 regions may play a critical role in AS pathogenesis across diverse populations.

Spondyloarthritis Patients Suffer Increased Risk of Renal Complications Compared With General Population: A Retrospective Observational Study.

The objective of this study was to identify the prevalence and risk factors of renal complications of spondyloarthritis (SpA) patients, and to assess increased risks compared to general people. We conducted a retrospective study enrolled with consecutive SpA patients from an inpatient department and age, sex-matched general population (GP). The renal disorders investigated in this study contained decreased estimated glomerular filtration rate (eGFR), hematuria, proteinuria and nephrolithiasis. A total of 350 admitted SpA patients with complete medical records and 323 age and sex-matched GP were enrolled. Most SpA patients were male (n = 283, 80.9%) and the mean age was 31.61 ± 10.73 years old. Among 350 SpA patients, 29 (8.8%) suffered from hematuria, six (1.8%) suffered from proteinuria, one (0.3%) had decreased eGFR, and 27 (13.0%) presented with nephrolithiasis. The relative risk (RR) of nephrolithiasis in SpA compared to the GP was 2.24 (95% CI, 1.00-4.98), and the RR of renal insufficiency was 2.04 (95% CI, 1.11-3.77). In a univariate analysis, nephrolithiasis was significantly associated with age, age of onset, smoking, extra-articular manifestation and a bamboo spine. Renal insufficiency was significantly associated with age, peripheral manifestation, serum albumin, C-reactive protein and erythrocyte sedimentation rate. In a multivariable analysis, only extra-articular manifestation (OR = 8.43, 95% CI, 1.65-43.06, p = 0.010) and bamboo spine (OR = 3.47, 95% CI, 1.01-12.06, p = 0.049) remained significantly associated with nephrolithiasis. However, no variable was recognized as an independent risk factor for renal insufficiency. Renal complications are more common in SpA patients, with more than two-fold increased risk compared with GP. Extra-articular manifestation and bamboo spine are independent risk factors of renal disease in SpA patients.

Using Mobile Apps for Health Management: A New Health Care Mode in China.

BACKGROUND: China has a large population; however, medical resources are unevenly distributed and extremely limited, and more medical services are needed. With the development and ever-increasing popularity of mobile internet communication, China has created a mode of mobile health (mHealth) care to resolve this problem. OBJECTIVE: The aim of this study was (1) to describe the problems associated with China's medical care practice, (2) explore the need for and the feasibility of internet-based medical care in China, and (3) analyze the functionality of and services offered by internet-based health care platforms for the management of chronic diseases. METHODS: Data search was performed by searching national websites, the popular search engine Baidu, the App Store, and websites of internet medical care institutions, using search terms like "mobile health," "Internet health," "mobile medical," "Internet medical," "digital medical," "digital health," and "online doctor." A total of 6 mobile apps and websites with the biggest enrollment targeting doctors and end users with chronic diseases in China were selected. RESULTS: We recognized the limitations of medical and health care providers and unequal distribution of medical resources in China. An mHealth care platform is a novel and efficient way for doctors and patients to follow up and manage chronic diseases. Services offered by these platforms include reservation and payment, medical consultation, medical education assessment, pharmaceutical and medical instruments sales, electronic medical records, and chronic disease management. China's health policies are now strongly promoting the implementation of mHealth solutions, particularly in response to the increasing burden of chronic diseases and aging in the population. CONCLUSIONS: China's internet-based medical and health care mode can benefit the populace by providing people with high-quality medical resources. This can help other countries and regions with high population density and unevenly distributed medical resources manage their health care concerns.

Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway.

The in vitro and in vivo effects of physalin D on macrophage M1/M2 polarization were investigated. In silico analysis was first performed for biological function prediction of different physalins. The results suggest physalins have similar predicted biological functions due to their similarities in chemical structures. The cytotoxicity of physalins was then analyzed based on cell apoptosis rate and cell viability evaluation. Physalin D was chosen for further study due to its minimal cytotoxicity. Bone marrow macrophages were isolated and induced with lipopolysaccharide/interferon (IFN)-γ for M1 polarization and interleukin (IL)-4/IL-13 for M2 polarization. The results showed that physalin D can repolarize M1 phenotype cells toward M2 phenotype. In addition, physalin D is protective in M2 macrophages to maintain the M2 phenotype in the presence of IFN-γ. On the molecular level, we found that physalin D suppressed the signal transducers and activators of transcription (STAT)1 activation and blocked STAT1 nuclear translocation. Conversely, physalin D can also activate STAT6 and enhance STAT6 nuclear translocation for M2 polarization. Taken together, these results suggested that physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway.