Search

This phase III trial (NCT04178850) evaluated the efficacy, safety, and immunogenicity of GB242, an infliximab biosimilar, vs. infliximab (Remicade®) reference product in patients with moderate-to-severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. Patients were randomized in a 1:1 ratio to receive either GB242 or INF (3 mg/kg). Therapeutic equivalence of clinical response according to the American College of Rheumatology 20% (ACR20) response rate at week 30 was declared if the two-sided 95% CI for the treatment difference was within ± 14%. The comparison of GB242 with INF also included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity. A total of 570 subjects were randomized into GB242 (N = 285) or INF (N = 285) and 283 subjects in each group were analyzed. At week 30, the ACR20 was 62.54% for the GB242 group (95% CI 56.62–68.20%) and 56.89% for the INF group (95% CI 50.90–62.74%). The difference between the two groups was 5.65% with a 95% CI of – 2.48 to 13.74. ACR50 response was 37.12% for GB242 and 32.86% for INF at week 30. ACR70 response was 19.79% for GB242 and 16.96% for INF at week 30, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs. 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs. 59.4% in INF) was comparable. GB242 demonstrated equivalent efficacy to INF at week 30. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF.

Objective To quantify the temporal trend of sex- and age-specific disability-adjusted life years (DALYs) for musculoskeletal (MSK) disorders by region and cause. Methods Data were collected from the Global Burden of Diseases Study 2019. The estimated annual percentage change (EAPC) by sex, age, region and cause was calculated to examine the temporal trend of the age-standardized DALYs rate (ASDR). The sociodemographic index (SDI) and risk exposures were also examined. Results Between 1990 and 2019, the global ASDR for MSK disorders remained almost stable by sex and age group but decreased among females ages 0–14 years (EAPC = −0.27). Such age and sex patterns were nearly the same by SDI, except for high SDI regions, where ASDR increased in all subgroups except those ages 15–49 years. The trend in ASDR of MSK disorders for females and males ages 50–74 and ≥75 years increased in ∼80% of countries and territories. The greatest increase was in El Salvador for males ages 15–49 years (EAPC = 1.30), followed by Nicaragua. The association between EAPC and SDI was positive in developing regions, particularly among females ages 15–49 years, and negative in developed regions. A decreasing trend in ASDR was mainly driven by the decrease in low back pain, while the increasing trend was largely due to other MSK disorders and gout across sexes and age groups. Conclusions There are great disparities in the age- and sex-specific trends in ASDR by cause on the global, regional and national levels. More differentiated prevention and management strategies are needed for MSK disorders.

Background The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients’ adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (健脾补肾续贯方, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer. Methods A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy. Discussion This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518)

The Internet of Things (IoT) play an important role in the financial sector in recent decades since several stock prediction models can be performed accurately according to IoT-based services. In real-time applications, the accuracy of the stock price fluctuation forecast is very important to investors, and it helps investors better manage their funds when formulating trading strategies. It has always been a goal and difficult problem for financial researchers to use predictive tools to obtain predicted values closer to actual values from a given financial data set. Leading indicators such as futures and options can reflect changes in many markets, such as the industry’s prosperity. Adding the data set of leading indicators can predict the trend of stock prices well. In this research, a trading strategy for finding stock trading signals is proposed that combines long short-term memory neural networks with genetic algorithms. This new framework is called long short-term memory neural network with leading index, or LSTMLI for short. We thus take the stock markets of the United States and Taiwan as the research objects and use historical data, futures, and options as data sets to predict the stock prices of these two markets. After that, we use genetic algorithms to find trading signals for the designed stock trading system. The experimental results show that the stock trading system proposed in this research can help investors obtain certain returns.

Rationale: Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation has been proved to be an effective therapeutic approach to treat systemic lupus erythematosus (SLE), the detailed underlying mechanisms are not fully understood. Transferring miRNAs is one mean by which MSCs communicate with surrounding cells. Sirt1 is a NAD-dependent deacetylase that protects against cell senescence by deacetylating p53. Here we aimed to explore whether hUC-MSCs affected senescence of splenic CD4+ T cells through regulating Sirt1/p53 via miRNA in the MRL/lpr lupus mouse model. Methods: The effects of hUC-MSCs on lupus syndrome and senescence pathways in MRL/lpr mice in vivo and in vitro were determined. The functional roles of miR-199a-5p in splenic CD4+ T cell senescence were studied by miRNA mimic or inhibitor in vitro. MRL/lpr mice were injected with miR-199a-5p agomir to evaluate the effects of miR-199a-5p on splenic CD4+ T cell senescence and disease in vivo. Results: We showed that hUC-MSCs transplantation ameliorated lupus symptoms and increased senescence of splenic CD4+ T cells through Sirt1/p53 signaling via miR-199a-5p in MRL/lpr mice. Moreover, systemic delivery of miR-199a-5p in MRL/lpr mice increased splenic CD4+ T-cell senescence, mimicking the therapeutic effects of transplanted hUC-MSCs. Conclusions: We have identified miR-199a-5p as one of the mechanisms employed by hUC-MSCs to alleviate lupus disease associated pathologies in MRL/lpr mice, which is attributable for promoting splenic CD4+ T cell senescence through Sirt1/p53 pathway.

Formulated as a conditional generation problem, face animation aims at synthesizing continuous face images from a single source image driven by a set of conditional face motion. Previous works mainly model the face motion as conditions with 1D or 2D representation ( e.g., action units, emotion codes, landmark ), which often leads to low-quality results in some complicated scenarios such as continuous generation and large-pose transformation. To tackle this problem, the conditions are supposed to meet two requirements, i.e., motion information preserving and geometric continuity. To this end, we propose a novel representation based on a 3D geometric flow, termed facial flow, to represent the natural motion of the human face at any pose. Compared with other previous conditions, the proposed facial flow well controls the continuous changes to the face. After that, in order to utilize the facial flow for face editing, we build a synthesis framework generating continuous images with conditional facial flows. To fully take advantage of the motion information of facial flows, a hierarchical conditional framework is designed to combine the extracted multi-scale appearance features from images and motion features from flows in a hierarchical manner. The framework then decodes multiple fused features back to images progressively. Experimental results demonstrate the effectiveness of our method compared to other state-of-the-art methods.

Background: Lupus nephritis (LN) is the most severe organ manifestations of systemic lupus erythematosus (SLE). Although increased knowledge of the disease pathogenesis has improved treatment options, outcomes have plateaued as current immunosuppressive therapies have failed to prevent disease relapse in more than half of treated patients. Thus, there is still an urgent need for novel therapy. Mesenchymal stem cells (MSCs) possess a potently immunosuppressive regulation on immune responses, and intravenous transplantation of MSCs ameliorates disease symptoms and has emerged as a potential beneficial therapy for LN. The objective of this review is to discuss the defective functions of MSCs in LN patients and the application of MSCs in the treatment of both LN animal models and patients. Summary: Bone marrow MSCs from SLE patients exhibit impaired capabilities of migration, differentiation, and immune regulation and display senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and patients with LN by inducing regulatory immune cells and suppressing Th1, Th17, T follicular helper cell, and B-cell responses. In addition, MSCs can home to the kidney and integrate into tubular cells and differentiate into mesangial cells. Key Messages: The efficacy of MSCs in the LN treatment remains to be confirmed, and future advances from stem cell science can be expected to pinpoint significant MSC subpopulations, as well as specific mechanisms of action, leading the way to the use of more potent stimulated or primed pretreated MSCs to treat LN.

To explore the association between the creatinine clearance rate (Ccr) and the prognosis of patients, and compared with estimated glomerular filtration rate (eGFR). We retrospectively collected information of patients with SLE who were first hospitalized between 1999 and 2009 in Jiangsu Province, China, and followed up in 2010 and 2015. Ccr was calculated and dichotomized into normal group (Ccr ≥ 70) and decreasing group (Ccr < 70). The clinical characteristics of the two groups were compared and Cox proportional-hazards regression models were used to calculate hazard ratio (HR) and 95% confidence interval (CI). Among 1990 SLE patients, we observed 437 (22.0%) with decreased Ccr, including 237 cases (11.9%) with mild renal dysfunction, 136 cases (6.8%) with moderate renal dysfunction, and 64 cases (3.2%) with severe renal dysfunction. Compared to normal Ccr, decreasing Ccr had a higher risk for mortality with adjusted HR (95% CI) of 2.21 (1.59–3.06). Dose-response relationships were significantly found between increased mortality of SLE and decreased Ccr (p for trend < 0. 001), as well as eGFR. Positive associations were consistently observed in subgroups, such as systemic lupus disease activity index (SLEDAI) ≥ 15, without comorbidities and abnormal laboratory indexes. Decreasing Ccr was positively associated with mortality from infection and renal failure with HR (95% CI) of 1.80 (1.02–3.19) and 6.84 (3.05–15.36). A significant association has been observed between decreased Ccr and increased risk for mortality of SLE patients. Early clinical interventions to modulate the Ccr of SLE patients may be beneficial to their survival.

Trastuzumab is a humanized mAb used to treat HER2-overexpressing breast cancer; however its mechanisms remain to be fully elucidated. Previous studies suggest a role for immunity in mediating trastuzumab-specific antitumor effects. This study evaluated the role(s) of trastuzumab and other antibodies on macrophage activation and Ab-dependent cell-mediated phagocytosis (ADCP) of HER2+ breast cancer cells in vitro and in vivo. We employed orthotopic implantation of HER2+ murine breast cancer (BC) cells in immunocompetent mouse models, a human HER2+ BC xenograft in an immune humanized mouse model, and human PDXs involving adoptive transfer of autologous macrophages to simulate an endogenous mammary tumor-immune microenvironment. Our study demonstrated that trastuzumab greatly and consistently increased macrophage frequency and tumor-cell phagocytosis, and that concurrent knockdown of B7-H4 by a neutralizing antibody increased immune cell infiltration and promoted an antitumor phenotype. Furthermore, neoadjuvant trastuzumab therapy significantly upregulated B7-H4 in the cancer-infiltrating macrophages of HER2+ BC patients, which predicted poor trastuzumab response. We suggest that strategies to specifically enhance ADCP activity might be critical to overcoming resistance to HER2 mAb therapies by inhibiting tumor growth and potentially enhance antigen presentation. Furthermore, these results advance the understanding of macrophage plasticity by uncovering a dual role for ADCP in macrophages involving elimination of tumors by engulfing cancer cells while causing a concomitant undesired effect by upregulating immunosuppressive checkpoints.

Background: Over half of patients with advanced cancer report appetite loss or anorexia. Previous studies have shown the benefit of acupuncture for cancer-related nausea and vomiting, but limited evidence exists for its role in appetite improvement. Our study aimed to evaluate the feasibility and safety of auricular acupuncture to improve appetite for cancer patients with advanced disease. Methods: We performed a two-arm parallel, pilot randomized controlled trial (RCT) of auricular acupuncture versus usual care control in patients with stage III or IV cancer who experienced appetite loss. The primary outcome was changed in the Simplified Nutritional Appetite Questionnaire (SNAQ; score range, 4–20) between two groups from baseline to weeks 2 and 4, with secondary outcomes including change in weight, as well as an additional evaluation at week 8 for durability of treatment effects. We used independent two-sample t-test for the change in mean score for each outcome during or after treatment. We assessed the interaction between time and treatment from baseline to weeks 2, 4, and 8 using mixed-effects models by ANOVA test. Results: We randomized 55 patients to auricular acupuncture (N=27) or control group (N=28). By week 4, the auricular acupuncture group had a significantly higher escalation in the SNAQ score than the control group compared with baseline [mean difference 3.69; 95% confidential interval (95% CI): 2.5, 4.8; P

As a particular type of artificial intelligence technology, machine learning (ML) is widely used to empower user experience (UX). However, designers, especially the novice designers, struggle to in...

Recently, interactive character control models based on neural network have become a hot research topic in computer graphics and motion synthesis. A real-time interactive character control model with two substructures called gated neural network is proposed in this paper. In the first part of the model, a gated network is used to calculate the expert weights based on the user’s input parameters and the character’s current pose dynamically. Mixture of experts is used in choosing different control strategies for user input. The character posture is controlled by selecting mode-adjustment or phase-adjustment. In the second part, a simple neural network is used to adjust the character’s state through additional input parameters on different landscapes and to synthesize the final character motion. Experimental results show that the model can improve the performance of character control.

Ankylosing spondylitis (AS) is a systemic, chronic, and inflammatory rheumatic disease that affects 0.2% of the population. Current diagnostic criteria for disease activity rely on subjective Bath Ankylosing Spondylitis Disease Activity Index scores. Here, we aimed to discover a panel of serum protein biomarkers. First, tandem mass tag (TMT)-based quantitative proteomics was applied to identify differential proteins between 15 pooled active AS and 60 pooled healthy subjects. Second, cohort 1 of 328 humans, including 138 active AS and 190 healthy subjects from two independent centers, was used for biomarker discovery and validation. Finally, biomarker panels were applied to differentiate among active AS, stable AS, and healthy subjects from cohort 2, which enrolled 28 patients with stable AS, 26 with active AS, and 28 healthy subjects. From the proteomics study, a total of 762 proteins were identified and 46 proteins were up-regulated and 59 proteins were down-regulated in active AS patients compared to those in healthy persons. Among them, C-reactive protein (CRP), complement factor H-related protein 3 (CFHR3), α-1-acid glycoprotein 2 (ORM2), serum amyloid A1 (SAA1), fibrinogen γ (FG-γ), and fibrinogen β (FG-β) were the most significantly up-regulated inflammation-related proteins and S100A8, fatty acid-binding protein 5 (FABP5), and thrombospondin 1 (THBS1) were the most significantly down-regulated inflammation-related proteins. From the cohort 1 study, the best panel for the diagnosis of active AS vs healthy subjects is the combination of CRP and SAA1. The area under the receiver operating characteristic (ROC) curve was nearly 0.900, the sensitivity was 0.970%, and the specificity was 0.805% at a 95% confidence interval from 0.811 to 0.977. Using 0.387 as the cutoff value, the predictive values reached 92.00% in the internal validation set (62 with active AS vs 114 healthy subjects) and 97.50% in the external validation phase (40 with active AS vs 40 healthy subjects). From the cohort 2 study, a panel of CRP and SAA1 can differentiate well among active AS, stable AS, and healthy subjects. For active AS vs stable AS, the area under the ROC curve was 0.951, the sensitivity was 96.43%, the specificity was 88.46% at a 95% confidence interval from 0.891 to 1, and the coincidence rate was 92.30%. For stable AS vs healthy humans, the area under the ROC curve was 0.908, the sensitivity was 89.29%, the specificity was 78.57% at a 95% confidence interval from 0.836 to 0.980, and the coincidence rate was 83.93%. For active AS vs healthy subjects, the predictive value was 94.44%. The results indicated that the CRP and SAA1 combination can potentially diagnose disease status, especially for active or stable AS, which will be conducive to treatment recommendation for patients with AS.

Video plays a great important role in online apparel sales, which is a vital tool for publicity and to provide consumers with space of imagination. However, as the apparel market rapidly updates in large amounts every day, creating videos for fast increasing clothes can be challenging and labor-consuming. Considering this, we present ApVideor, a music-driven video generation system customized for displaying clothes. This system consists of two main modules: music recommendation module and audio-visual synthesis module. The former assists users in searching background music that matches the apparel style, while the latter combines the audio and visuals into a video by music-driven approaches. Our user study suggests that this system makes the video creation process significantly easier and faster than manual creation. Meanwhile, the viewer test suggests that apparel-displaying videos created using our system are of comparable quality to those created manually by people who have worked with video editing.

Artificial intelligence (AI) has played a significant role in imitating and producing large-scale designs such as e-commerce banners. However, it is less successful at creative and collaborative design outputs. Most humans express their ideas as rough sketches, and lack the professional skills to complete pleasing paintings. Existing AI approaches have failed to convert varied user sketches into artistically beautiful paintings while preserving their semantic concepts. To bridge this gap, we have developed SmartPaint, a co-creative drawing system based on generative adversarial networks (GANs), enabling a machine and a human being to collaborate in cartoon landscape painting. SmartPaint trains a GAN using triples of cartoon images, their corresponding semantic label maps, and edge detection maps. The machine can then simultaneously understand the cartoon style and semantics, along with the spatial relationships among the objects in the landscape images. The trained system receives a sketch as a semantic label map input, and automatically synthesizes its edge map for stable handling of varied sketches. It then outputs a creative and fine painting with the appropriate style corresponding to the human’s sketch. Experiments confirmed that the proposed SmartPaint system successfully generates high-quality cartoon paintings.

Origami is the art of making 2D/3D shapes by folding paper, HCI researchers have leveraged novel structure design and material techniques to create a wide range of origami-based shape-changing interface. Meanwhile, additive manufacturing which could easily fabricate complicated artifacts and augment the haptic sensation, has drawn more attention to the field. This paper presents 3DP-Ori, a fabrication method of flexible origami construction with conventional FDM printers. To create and end-to-end pipeline, we developed a parametric design tool with dynamic folding simulation and feasibility estimation, which enable our software to output a printable semi-folded origami model for further easy manual deformation. Adopting and optimizing bridging-based printing, we leverage multiple geometric patterns with adjustable flexibility on creases, which further effect the haptic properties on 3DP-Ori objects. We believe the 3DP-Ori extends the design space of 3D printing beyond typically hard and fixed forms, and it will help designers and researchers to fabricate interactivities with various physical properties.

Objective Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of patients with primary Sjögren’s syndrome and to correlate these findings with their disease activity. Methods Fifty-two patients with primary SS and 52 sex- and age-matched healthy control subjects were included. All of them underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerized testing including the three stages of smell: threshold, identification, and memory of the different odors. Results All the olfactory scores (olfactory threshold, identification, and memory) in patients with pSS were significantly decreased than the control group (all P < 0.01). Patients had higher proportion of anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) than controls (χ2 = 10.526, P < 0.01). Multivariable regression analysis revealed that ESSDAI and the symptoms of dryness, fatigue, and limb pain had negative influence on olfactory function (adjusted R2 = 0.381, 0.387, 0.513, and 0.614, respectively). ESSPRI showed significantly negative association with olfactory threshold, identification, memory, and total scores. Olfactory identification and memory scores were decreased in pSS patients with thyroid dysfunction or hypocomplementemia (P < 0.05). Smell threshold scores were decreased in pSS patients with anti-SSA antibody or anti-nuclear antibody compared with those without those autoantibodies (P < 0.01). Conclusion Our findings indicate that olfactory functions are impaired in pSS patients. There was a close correlation between olfactory dysfunction and disease severity and immunological abnormalities. Immune and systemic inflammation dysregulation might play a role in the mechanism of this defect.

Autoreactive T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). TGF-β type I receptor (TGFβRI) is pivotal in determining T cell activation. Here, we showed that TGFβRI expression in naïve CD4+ T cells was decreased in SLE patients, especially in those with high disease activity. Moreover, IL-6 was found to downregulate TGFβRI expression through JAK/STAT3 pathway in SLE patients. In vitro, the JAK inhibitor tofacitinib inhibited SLE T cell activating by upregulating TGFβRI expression in a dose-dependent manner. In MRL/lpr mice, tofacitinib treatment ameliorated the clinical indicators and lupus nephritis, as evidenced by reduced plasma anti-dsDNA antibody levels, decreased proteinuria, and lower renal histopathological score. Consistently, tofacitinib enhanced TGFβRI expression and inhibited T cell activation in vivo. TGFβRI inhibitor SB431542 reversed the effects of tofacitinib on T cell activation. Thus, our results have indicated that tofacitinib can suppress T cell activation by upregulating TGFβRI expression, which provides a possible molecular mechanism underlying clinical efficacy of tofacitinib in treating SLE patients.

OBJECTIVE To explore the role of diffusion kurtosis magnetic resonance (MR) imaging in the noninvasive identification of synovitis in hand arthritis. METHODS A total of 30 patients with rheumatoid arthritis (RA) and 10 patients suspected of RA were enrolled in the prospective study. A 3.0-T MR imaging including the diffusion kurtosis MR imaging sequence (b = 0, 500, 1000, 1500, 2000 s·mm2) was performed. A total of 210 regions of interest were confirmed and diffusion kurtosis MR imaging parameters were generated. The suspected synovitis or effusion was scored on a scale of 0 (effusion) to 3 (mild, moderate, severe synovitis), according to RA-MR imaging scoring system. The performance of diffusion kurtosis MR imaging parameters (the apparent diffusion coefficient [ADC], diffusion coefficient [D], and kurtosis [K]) in distinguishing different synovitis scores was evaluated. RESULTS There were significant differences in ADC, D, and K values among different synovitis scores (all P < 0.001). Synovitis scores were negatively correlated with the ADC and D values significantly (r = -0.725, -0.757, respectively, all P < 0.001), but positively correlated with the K values significantly (r = 0.429, P < 0.001). The area under the curve values of D, ADC, and K values were 0.884, 0.874, and 0.728 for differentiating score 1-3 from score 0, respectively. Diffusion coefficient and ADC had similar diagnostic performance, and both were higher than K in detecting synovitis. No significant difference was found between the ADC and D values in detecting synovitis. CONCLUSIONS The diffusion kurtosis MR imaging may be feasible as a noninvasive method for the diagnosis and grading of synovitis in the hands of RA patients, and the D and ADC values showed similar diagnostic performance, both of which were higher than K values.

Introduction: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. Methods: We developed an initial 8-item TCM-SDS scale for CRC based on literature review and consultation with experts. We then pilot tested the scale ( n = 40) and performed item revision. We conducted a survey study among CRC patients from oncology clinics at a TCM Hospital to further determine the reliability and validity of the scale. Results: Among 100 patients finally enrolled and analyzed in the survey study, 46% were female with median age of 60 years old, 77% had left side tumors and 23% had stage IV disease. Factor loading indicated that there were three domains within TCM-SDS scale. The final TCM-SDS scale involves 5 items including “I feel loss of appetite,” “I feel abdomen fullness,” “I feel my arms and legs lack strength,” “I feel short of breath when talking,” and “My stool is formless” (Cronbach’s alpha coefficient 0.76). We calculated the total score of the scale by summing the 5 individual items and normalizing them to a value maximum of 10, with higher scores indicating greater burden of spleen deficiency syndrome. The average spleen deficiency score for all patients was 3.55 ± 1.54. Among them, those who had stage IV disease had higher scores than stage I-III patients (4.30 vs 3.38, P = .015). Test-retest reliability after 2 weeks showed Pearson coefficient of 0.67 and all items were highly related ( P Conclusion: The patient-reported TCM-SDS scale for CRC showed adequate initial reliability and validity. The development of the scale provided an outcome measurement tool, which could facilitate future studies to better evaluate the role of TCM in treating CRC.

Objective: To evaluate the effectiveness of Chinese Herbal Medicine (CHM) on leukopenia/neutropenia induced by chemotherapy in adults with colorectal cancer (CRC). Methods: Eight electronic databases were searched from their inception to June 2020. Randomized controlled trials with clarified sequence generation were qualified. Two reviewers independently conducted the screening and data extraction. Methodological quality was assessed using the Risk of Bias tool. RevMan 5.4 was applied to the meta-analysis. Results: Twenty-seven studies involving 1867 participants were qualified, of which 26 were included in the quantitative synthesis. Meta-analysis showed that CHM significantly reduced the incidence of leukopenia induced by chemotherapy (RR = 0.69; 95% CI 0.59-0.82), as well as the grade 3/4 leukopenia (RR = 0.71; 95% CI 0.55-0.90). Meanwhile,CHM decreased the occurrence of neutropenia (RR = 0.52, 95% CI 0.35-0.77), especially for the grades 3/4 neutropenia (RR = 0.42, 95% CI 0.27-0.64). Twenty-six of the included studies focused on the adverse events related to CHM. Conclusion: CHM may relieve neutropenia/leukopenia induced by chemotherapy in adults with colorectal cancer.

Rationale: Although mesenchymal stem cell (MSC) transplantation has been proved to be an effective therapeutic approach to treat experimental Sjogren's syndrome (SS), the detailed underlying mechanisms remains unknown. IL-27 has diverse influences on the regulation of T cell differentiation and was involved in SS through modulating immune response. Here we aimed to explore whether IL-27-mediated regulation of immune cells was responsible for the beneficial effects of MSC transplantation on SS. Methods: The SS-like symptoms were evaluated in IL-27 deficient and recombinant IL-27-treated NOD mice. The MSCs were infused into NOD mice via the tail vein. The histological features of submandibular glands, saliva flow rate and serum IL-27 were examined. The effects of MSCs on the IL-27 production and Th17/Treg cell in SS patients and mice in vitro and in vivo were determined for the mechanistic study. Results: This study showed that SS patients had decreased IL-27 level and increased ratio of Th17/Treg cells. Consistently, exacerbated SS-like symptoms were observed in IL-27 deficient NOD mice, along with increased ratio of Th17/Treg cells. Importantly, MSC transplantation alleviated SS-like symptoms by elevating the level of IL-27 to restore Th17/Treg balance in NOD mice. Mechanistically, MSC-secreted interferon-β (IFN-β) promote dendritic cells to produce IL-27. Conclusions: Thus, we have revealed a previously unrecognized function of MSC-mediated IL-27 production by DCs in suppressing SS-like syndrome, which provided evidences for clinical application of MSC in patients with SS.

Infection is a common cause of hospitalization and mortality in patients with systemic lupus erythematosus (SLE). How the underlying immune dysfunctions affect the antimicrobial immunity remains largely unknown. In the present study, employing the pulmonary infection model, we determined the antimicrobial defence of lupus-prone mice. After infecting with opportunistic bacterium Haemophilus influenzae (Hi), lupus-prone mice (B6/lpr) exhibited inefficient bacterial elimination and recovered slowly. They generated severer inflammation at the early stage of infection, as excessive accumulation of neutrophils and enhanced production of proinflammatory cytokines were observed in the lung. In addition, a large number of apoptotic cells were detected in the lungs of B6/lpr mice. For adaptive immune responses, B6/lpr mice were capable to generate enough protective Hi-specific Th17 cells. They evoked stronger Hi-specific γδ T17 response in both lungs and spleens. Unexpectedly, both CD4 and γδ T cells from lupus-prone mice showed deficiency in IFN-γ production. For humoral immune responses, compared with those of WT mice, the concentrations of Hi-specific IgA, IgM, and IgG, especially IgG, were significantly higher in the B6/lpr mice. Our findings suggest that lupus mice are capable to generate antibacterial immune responses; however, the overwhelming inflammation and overactivated immune responses increase the severity of infection.

Background Defective clearance of apoptotic cells (ACs) has been suggested to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) exhibit promising therapeutic effects on SLE, but whether MSCs phagocytose ACs and contributes to the underlying mechanism in the treatment of SLE remain unknown. Methods Human umbilical cord (UC) MSCs were co-cultured with ACs, and the engulfment of ACs by MSCs was either detected by flow cytometry or observed under confocal laser scanning microscope. Peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) were cultured in MSC conditioned medium (MCM) or MSC exposed to ACs (AC-MSC) conditioned medium (ACMCM), and then CD4+ T cell proliferation was detected. Soluble factors including prostaglandin (PG)E2 in the supernatants of MSCs and AC-MSCs, as well as in the mouse peritoneal lavage fluids (PLF) were determined by enzyme-linked immunosorbent assay (ELISA). Cyclooxygenase (COX)2 inhibitors and siRNA transfection were utilized to determine the function of COX2/PGE2 in AC-MSC-mediated immunosuppression. PGE2 metabolites (PGEM) in the plasma of SLE patients were measured before and 24 h after MSC transplantation respectively. Findings Human UC MSCs possessed the ability to engulf ACs. AC-MSCs increased MSC-mediated suppression of CD4+ T cell proliferation compared to MSCs alone. Mechanistically, ACs stimulated MSCs to express COX2 and consequently produced PGE2 that inhibited T cell responses. NF-κB signalling pathway mediated the activation of COX2/PGE2 in AC-MSCs. Importantly, in patients with SLE, the plasma PGEM levels increased significantly in those with reduced apoptotic mononuclear cells in peripheral blood after MSC transplantation. Interpretation Clearance of ACs by MSCs contributes to immunosuppressive function via increasing PGE2 production. These findings reveal a previously unrecognized role of MSC-mediated phagocytosis of ACs in MSC-based immunotherapy. Fund This study was supported by grants from the Chinese Major International (Regional) Joint Research Project (No. 81720108020), the Jiangsu Province Major Research and Development Program (No. BE2015602) and the Jiangsu Province 333 Talent Grant (BRA2016001). WJ. Chen was supported by the Intramural Research Program of NIH, NIDCR.

Triptolide is a biologically active component of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown to be effective in treating murine lupus. However, its immunological mechanisms are poorly understood. Regulatory T cells (Treg) are pivotal for maintaining peripheral self-tolerance and controlling autoimmunity. This study was undertaken to examine the therapeutic effect of triptolide in lupus mice and the related molecular mechanisms. Our results showed that triptolide treatment ameliorated serum anti-dsDNA, proteinuria and renal histopathologic assessment in MRL/lpr mice, induced the miR-125a-5p expression and enhanced the proportion of Treg in vivo. In vitro, triptolide upregulated the proportion of Treg and the miR-125a-5p expression. Down-regulation of the miR-125a-5p expression reversed the effect of triptolide on Treg. In conclusion, triptolide could induce Treg and the miR-125a-5p expression in vivo and in vitro. Inhibiting the effect of miR-125a-5p could counteract the effect of triptolide on inducing Treg. The study has strong implications for the therapeutic applications of triptolide in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a broad range of clinical manifestations and a heterogeneous disease course. There is no cure for SLE, but current standard pharmacotherapies can improve disease prognosis in most patients. However, some patients are refractory to conventional treatments and require alternative treatment options. The present study is aimed at identifying predictors of clinical response to allogeneic bone marrow-derived or umbilical cord-derived mesenchymal stem cell (BM-/UC-MSC) transplant in SLE. All adult patients identified in the Nanjing database with an SLE Disease Activity Index (SLEDAI) score≥8 at baseline that had undergone MSC transplant and who had at least 1 year of follow-up after one or two successive intravenous injections of allogeneic BM-/UC-MSCs (1 million/kg) were analyzed. SLE symptoms and SLEDAI were assessed at baseline and during follow-up to determine low disease activity (LDA) and clinical remission (CR) at 1, 3, 6, and 12 months. Sixty-nine patients were included in the study, with a median (range) SLEDAI of 13 (8-34) at baseline. Among the 69 patients, 40 (58%) achieved LDA and 16 (23%) achieved CR with a SLEDAI of 9 (4–20), 8 (0-16), 6 (0-18), and 5 (0-18) after 1, 3, 6, and 12 months, respectively. Older age (p=0.006) and no arthralgia/arthritis at baseline (p=0.03) were associated with a higher rate of LDA. Achieving CR was associated with older age (p=0.033), no arthralgia/arthritis at baseline (p=0.001), and no prior use of cyclophosphamide (p=0.003) or hydroxychloroquine (p=0.016). Future studies using unique immunosuppressive regimens and allogeneic MSC sources will further elucidate determinants of clinical response to MSC transplant in SLE.

Aim Cardiovascular complications related to atherosclerosis are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the underlying mechanisms are not fully understood. Endothelial dysfunction has been identified as having involvement in pathogenesis of cardiovascular diseases and SLE. This study aims to evaluate endothelial cell injury in mice with the combination of lupus and atherosclerosis. Methods The mouse model of accelerated atherosclerosis in lupus (gld.apoE- / - mouse) was generated from apolipoprotein E-deficient (apoE- / - ) and Faslgld C57BL/6 mice. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. The endothelial cell injury was determined. Results The results showed that the double-mutant gld.apoE- / - mice were generated. Spleens from 5-month-old gld.apoE- / - mice were significantly enlarged compared with wild-type mice (WT mice). The gld.apoE- / - mice produced high levels of total immunoglobulin G (IgG) and IgM and showed marked increase of IgG and C3 deposits in the glomeruli. The gld.apoE- / - mice displayed a pattern of glomerulonephritis typically found in SLE. The gld.apoE- / - mice have high levels of serum creatinine. The total cholesterol, low-density lipoprotein cholesterol and triglycerides were significantly increased, while high-density lipoprotein cholesterol decreased in the double-mutant mice. The circulating endothelial progenitor cells were significantly decreased. The serum levels of thrombomodulin and vascular cell adhesion molecule-1 were significantly elevated in gld.apoE- / - mice. The gld.apoE- / - mice simultaneously exhibited SLE and atherosclerosis characteristics. Conclusion Our findings indicated that endothelial cell injury might be a biomarker for evaluating risks of cardiovascular disease in SLE and targeting endothelial cell dysfunction might prevent and treat atherosclerosis in SLE.

BACKGROUND Conventional MRI is limited in quantitative evaluation of ankylosing spondylitis (AS) activity states. A comparison of the effectiveness of the whole-lesion apparent diffusion coefficient (ADC) histogram analysis with the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index in evaluating the disease activity of AS might aid in this assessment. PURPOSE To compare the effectiveness of the whole-lesion ADC histogram analysis with the SPARCC MRI index in evaluating the disease activity states of AS. STUDY TYPE Prospective. POPULATION A total of 57 AS patients and 27 healthy matched volunteers were included. FIELD STRENGTH/SEQUENCE 3.0T MR including a diffusion-weighted imaging (DWI) sequence (b = 0, 1000 s/mm2 ). STATISTICAL TESTS One-way analysis of variance (ANOVA) and Scheffe's post-hoc was used to compare the parameters among different groups. A receiver operating characteristic (ROC) analysis and the Spearman rank correlation were performed to test the diagnostic performance of all parameters in distinguishing different disease activity states and determining the correlations between them. ASSESSMENT AS disease activity states was evaluated according to the Ankylosing Spondylitis Disease Activity Score (ASDAS). Initial DWI images and corresponding ADC maps were imported into our in-house software. Regions of interest (ROIs) were drawn in all slices and the relevant parameters were derived simultaneously. The SPARCC MRI index scores were counted artificially based on T2 -PDW-SPAIR images. RESULTS The ADCmean , ADC percentiles, and SPARCC MRI index of the active group were significantly higher than the inactive and control groups (all P

Resolvin D1 (RvD1) prompts inflammation resolution and regulates immune responses. We explored the effect of RvD1 on systemic lupus erythematosus (SLE) and investigated the correlation between RvD1 and Treg/Th17 imbalance, which is one of the major factors contributing to the pathogenesis of disease. SLE patients and healthy controls were recruited to determine plasma RvD1 levels. MRL/lpr lupus model was used to verify rescue of the disease phenotype along with Treg/Th17 ratio. Purified naive CD4+ T cells were used to study the effect of RvD1 on Treg/Th17 differentiation in vitro. Furthermore, small RNA Sequencing and transfection were performed successively to investigate downstream microRNAs. The result showed that the RvD1 level was significantly lower in active SLE patients compared with inactive status and controls. Moreover, The SLE disease activity index (SLEDAI) score had a significant negative correlation with RvD1 level. As expected, RvD1 treatment ameliorated disease phenotype and inflammatory response, improved the imbalanced Treg/Th17 in MRL/lpr mice. In addition, RvD1 increased Treg while reduced Th17 differentiation in vitro. Furthermore, miR-30e-5p was verified to modulate the Treg/Th17 differentiation from naïve CD4+ T cells as RvD1 downstream microRNA. In conclusion, RvD1 effectively ameliorates SLE progression through up-regulating Treg and down-regulating Th17 cells via miR-30e-5p.

This demo presents FlexTruss, a design and construction pipeline based on the assembly of modularized truss-like objects fabricated with conventional 3D printers and assembled by threading. To create an end-to-end system, a parametric design tool with an optimal Euler path calculation method is developed, which can support both inverse and forward design workflow and multi-material construction of modular parts. In addition, the workflow guides the assembly of printed truss modules by threading. Finally, a series of application cases to demonstrate the affordance of FlexTruss are presented. We believe that FlexTruss extends the design space of 3D printing beyond typically hard and fixed forms, and it will provide new capabilities for designers and researchers to explore the use of such flexible truss structures in human-object interaction.

Background: This double-blind, active-controlled, randomized, multicenter phase III study evaluated the efficacy, safety and immunogenicity of GB242, an infliximab biosimilar, vs infliximab (Remicade®) reference product in patients with moderate to severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy.Methods: Patients randomised in a 1:1 ratio to receive either GB242 or INF (3 mg/kg intravenous at weeks 0, 2, 6, 14 and 22). MTX was given as an oral weekly dose of 10–25 mg/week with folic acid of 5–10 mg/week, 30 times totally. The primary end point was the American College of Rheumatology 20% (ACR20) response rate at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was declared if the two-sided 95% CI for the treatment difference was within ±14%. Statistical analysis was also performed with a two-sided 95% CI using ±14% margin. Secondary endpoints included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity of GB242.Results: 570 subjects were randomized into GB242 (N=285) or INF (N=285). Finally, 283 subjects in each group were analysed. The primary endpoint was the ACR20 response. In the full analysis population, 177 (62.54%) of 283 patients in the GB242 group (95% CI 56.62% – 68.20%) and 161 (56.89%) of 283 patients in the INF group (95% CI 50.90% – 62.74%) reached ACR20 at week 30. The difference between the two groups was 5.65% with a 95% CI of -2.48 to 13.74, which was within the predefined equivalence margin. The ACR20 response was also similarly shown in the PPS; ACR20 was 71.73% for GB242 and 66.52% for INF, respectively. The difference between the two groups was 5.21% with a 95% CI of -3.33 to 13.6, which was within the predefined equivalence margin. The second endpoints outcomes such as ACR50 response rate, ACR70 response rate and DAS28 were similar between GB242 and INF. ACR50 response for the FAS was 37.12% for GB242 and 32.86% for INF，ACR50 response for the PPS was 42.62% for GB242 and 38.63% for INF. ACR70 response for the FAS was 19.79% for GB242 and 16.96% for INF, ACR70 response for the PPS was 22.78% for GB242 and 20.63% for INF, respectively. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs 59.4% in INF) was comparable.Conclusions: The efficacy of GB242 appeared to be slightly better than that of INF in terms of ACR20, ACR50, ACR70 at week 30, but the difference was not statistically significant. Moreover, GB242 was well tolerated, with a similar immunogenicity and safety profile comparable to INF. Trial registration: CTR20170127, registered 28 July 2017; NCT04178850, registered 26 Nov 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04178850?term=GB242&draw=2&rank=1

3D printing, as a rapid prototyping technique, usually fabricates objects that are difficult to modify physically. This paper presents FlexTruss, a design and construction pipeline based on the assembly of modularized truss-shaped objects fabricated with conventional 3D printers and assembled by threading. To create an end-to-end system, a parametric design tool with an optimal Euler path calculation method is developed, which can support both inverse and forward design workflow and multi-material construction of modular parts. In addition, the assembly of truss modules by threading is evaluated with a series of application cases to demonstrate the affordance of FlexTruss. We believe that FlexTruss extends the design space of 3D printing beyond typically hard and fixed forms, and it will provide new capabilities for designers and researchers to explore the use of such flexible truss structures in human-object interaction.

3D printing technology makes Do-It-Yourself and reforming everyday objects a reality. However, designing and fabricating attachments that can seamlessly adapt existing objects to extended functionality is a laborious process, which requires accurate measuring, modeling, manufacturing, and assembly. This paper presents ShrinCage, a 4D printing system that allows novices to easily create shrinkable adaptations to fit and fasten existing objects. Specifically, the design tool presented in this work aid in the design of attachment that adapts to irregular morphologies, which accommodates the variations in measurements and fabrication, subsequently simplifying the modeling and assembly processes. We further conduct mechanical tests and user studies to evaluate the availability and feasibility of this method. Numerous application examples created by ShrinCage prove that it can be adopted by aesthetic modification, assistive technology, repair, upcycling, and augmented 3D printing.

Alerting customers on suspected online-payment fraud and persuade them to terminate transactions is increasingly requested with the rapid growth of digital finance worldwide. We explored the feasibility of using a conversational agent (CA) to fulfill this request. Shing, a voice-based CA, proactively initializes and repairs the conversation with empathetical communication skills in order to alert customers when a suspected online-payment fraud is detected, collects important information for fraud scrutiny and persuades customers to terminate the transaction once the fraud is confirmed. We evaluated our system by comparing it with a rule-based CA with regards to customer response and perceptions in a real-world context where our systems took 144,795 phone calls in total in which 83,019 (57.3%) natural breakdowns happened. Results showed that more customers stopped risky transactions after conversing with Shing. They seemed more willing to converse with Shing for more dialogue turns and provide transaction details. Our work presents practical implications for the design of proactive CA.

Objective To investigate the changes of olfactory function and odor-induced brain activation in patients with systemic lupus erythematosus (SLE) at early stages compared with healthy controls. Materials and Methods Olfactory function and odor-induced brain activation in 12 SLE patients at early stages and 12 age, gender and education matched healthy controls were evaluated using olfactory behavior test and odor-induced task-functional magnetic resonance imaging (task-fMRI). Results No significant differences in olfactory behavior scores (including olfactory threshold, olfactory identification, and olfactory memory) were found in the patients with SLE at early stages compared with the healthy controls, while significantly decreased odor-induced activations in olfactory-related brain regions were observed in the patients. In the SLE group, the patients with better performance in the olfactory threshold test had significantly lower levels of anti-dsDNA antibody. Conclusion The current study demonstrated that significant alterations in odor-induced brain activations occurred prior to measurable olfactory decline in SLE at early stages, which provided a new method for early diagnosis of olfactory dysfunction in SLE.

Medical patches have been widely explored and applied in various medical fields, especially in wound healing, tissue engineering, and other biomedical areas. Benefiting from emerging biomaterials and advanced manufacturing technologies, great achievements have been made on medical patches to evolve them into a multifunctional medical device for diverse health-care purposes, thus attracting extensive attention and research interest. Here, we provide up-to-date research concerning emerging functional biomaterials as medical patches. An overview of the various approaches to construct patches with micro- and nanoarchitecture is presented and summarized. We then focus on the applications, especially the biomedical applications, of the medical patches, including wound healing, drug delivery, and real-time health monitoring. The challenges and prospects for the future development of the medical patches are also discussed.

Objectives: This double-blind, active-controlled, randomized, multicenter phase III study evaluated the efficacy, safety and immunogenicity of GB242 , an infliximab biosimilar, vs infliximab (Remicade®) reference product in patients with moderate to severe active rheumatoid arthritis (RA) combination with methotrexate (MTX) therapy. Methods: Patients randomised in a 1:1 ratio to receive either GB242 or INF (3 mg/kg intravenous at weeks 0, 2, 6, 14 and 22). MTX was given as an oral weekly dose of 10–25 mg/week with folic acid of 5–10 mg/week, 30 times totally. The primary end point was the American College of Rheumatology 20% (ACR20) response rate at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was declared if the two-sided 95% CI for the treatment difference was within ±14%. Statistical analysis was also performed with a two-sided 95% CI using ±14% margin. Secondary endpoints included the proportion of patients achieving a week 30 ACR 50 response, ACR70 response, change in Disease Activity Score 28 (DAS28), as well as safety and immunogenicity of GB242.Results: 570 subjects were randomized into GB242 (N=285) or INF (N=285). Finally, 283 subjects in each group were analysed. The primary endpoint was the ACR20 response. In the full analysis population, 177 (62.54%) of 283 patients in the GB242 group (95% CI 56.62% – 68.20%) and 161 (56.89%) of 283 patients in the INF group (95% CI 50.90% – 62.74%) reached ACR20 at week 30. The difference between the two groups was 5.65% with a 95% CI of -2.48 to 13.74, which was within the predefined equivalence margin. The second endpoints outcomes such as ACR50 response rate, ACR70 response rate and DAS28 were similar between GB242 and INF. The incidence of treatment-emergent adverse events was comparable (77.4% in GB242 vs 80.2% in INF) and detection of antidrug antibodies (ADA) to infliximab up to week 30 (60.8% in GB242 vs 59.4% in INF) was comparable. Conclusions: GB242 demonstrated equivalent efficacy to INF at week 30, with a similar immunogenicity. GB242 was well tolerated, with a safety profile comparable to INF. Trial Registration: ClinicalTrials.gov NCT04178850 Funding: This study was funded by Genor Biopharma Co., Ltd., China. Declaration of Interest: None to declare. Ethical Approval: The study was conducted according to the Declaration of Helsinki and the International Committee on Harmonisation good clinical practice and all applicable regulatory requirements. The study protocol was reviewed and approved by independent ethics committees of each study site. All patients provided written informed consent.

We appreciate Chiang et al 1 for their interest and comments on our research article entitled ‘Incidence trend of five common musculoskeletal disorders from 1990 to 2017 at the global, regional and national level: results from the global burden of disease study 2017’.2 For exact occupations, it is unfortunately impossible to divide patients with musculoskeletal (MSK) disorders into groups according to their occupations since there are no corresponding estimates from the Global Burden of Disease study 2017.3 4 We agree with your comments on effects of social risk factors and occupational risks between high and low human development index (HDI) countries1; in our study, a stable or increasing trend of age-standardised incidence rate (ASR) for low back pain (LBP) was observed.2 However, occupational risks attributable to ASR might be more likely to be modified among countries …

IntroductionA considerable proportion of patients with systemic lupus ery­thematosus (SLE) have liver enzyme abnormalities. We evaluated whether fibrosis-4 (FIB-4) was associated with increased mortality of SLE patients.Material and methodsA multicenter retrospective cohort study was conducted based on medical records of first-admission SLE patients who were hospitalized during 1999–2009 in Jiangsu province. FIB-4 was estimated by age, platelet (PLT) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and FIB-4. A Cox model and a restricted cubic spline (RCS) model were used to estimate hazard ratio (HR) and 95% confidence interval (95% CI).ResultsDuring up to 15 years of follow-up, 226 deaths were observed among 2331 SLE patients. Increased overall mortality was associated with abnormal groups of PLT, ALT, AST, and high FIB-4 (≥ 1.92), with adjusted HRs (95% CI) of 1.58 (1.19–2.11), 1.54 (1.14–2.07), 1.58 (1.17–2.12), and 1.88 (1.42–2.50), respectively. Moreover, significant dose-response relationships were found between mortality of SLE and those indexes, and it was nonlinear for PLT (p < 0.001), ALT (p = 0.046) and FIB-4 (p < 0.001), but not AST (p = 0.109). In cause-specific analyses, high FIB-4 index was directly associated with death from liver failure and indirectly associated with other death from infection and neuropsychiatric impairment. We found no significant differences of areas under curves (AUCs) between FIB-4 index and the disease activity index score of SLE.ConclusionsThis is the first report to describe the nonlinear association between FIB-4 index and increased mortality of SLE patients. The FIB-4 index may be used as an independent prognostic indicator for SLE patients.

Aim: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. Method: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. Results: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. −0.76, P = .002), Collinsella (coef.−0.61, P = .02), Ruminiclostridium_9 (coef. −0.64, P = .01). Conclusion: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.

Digital fabrication allows users to produce physical objects from digital models. However, conventional fabrication processes are mostly irreversible: once an object is fabricated, it is detached from its original virtual model and cannot be physically changed. In this work, we propose WireTruss, a novel approach for rapid prototyping truss mesh structures, which can be rapidly fabricated, easily assembled and manually modified to support an intuitive design iteration. We developed a parametric design tool that first simplifies the object into a truss graph composed of multi-way joints, and then calculates the route of the wire which is inherently a Euler path. Furthermore, WireTruss can be demonstrated its practical usability through a series of application cases.

Textiles encompass a wide variety and rich characteristics that ranges from soft to tough, foldable to rigid, cuttable to stiff, elastic to plastic. On the other hand, 3D printing thermoplastic (e.g., PLA) materials exhibit controlled deformation at a certain transition temperature. In this paper, we present a method of fabricating form-fitting composite textiles by printing PLA on different fabric substrates, designing different structures and transforming the fabric-PLA composite to form different textures.

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR’97), 2012 Systemic Lupus International Collaborating Clinics (SLICC’12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR’19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC’12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR’19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.

Objective To evaluate serum concentration and activity of angiotensin-converting enzyme 2 (ACE2) in patients with connective tissue diseases (CTDs). Methods Serum samples from healthy subjects and patients with SLE, systemic sclerosis (SSc), primary Sjögren’s syndrome (SS) and RA were collected. The concentration and activity of ACE2 were measured by ELISA and fluorometric method, respectively, and analysed for associations with clinical features and concurrent medications. Results In total, 66 SLE, 55 SSc, 31 SS and 31 RA patients were involved. ACE2 concentration was significantly decreased in patients with either of the four CTDs compared with healthy subjects. The concentration was not linked to special clinical features expect that it was slightly lower in patients with lupus nephritis than those without. In SLE patients, ACE2 concentration elevated with the increase of glucocorticoids, and was not associated with other treatments. Different from the concentration, ACE2 activity was increased in CTD patients. A weak correlation of ACE2 activity with SLE disease activity index score was also observed. Conclusion The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggest ACE2 levels are not affected by most of the treatments.

BACKGROUND: Lipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets. METHODS: The expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/lpr mice and analyzing pristane-treated LCN2(−/−) mice. RESULTS: LCN2 is highly expressed in CD4(+) T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-γ overexpression in CD4(+) T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/lpr mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells. CONCLUSIONS: LCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN.

As simulators of organisms in Nature, soft robots have been developed over the past few decades. In particular, biohybrid robots constructed by integrating living cells with soft materials demonstrate the unique advantage of simulating the construction and functions of human tissues or organs, thus attracting extensive attention and research interest. Here, we present up-to-date studies concerning biohybrid robots with various biological actuators such as contractile cells and microorganisms. After presenting the basic components including biological components and synthetic materials, the controlling methods and locomotion modalities of biohybrid robots are clarified and summarized. We then focus on the applications, especially the biomedical applications, of the biohybrid robots including drug delivery, bioimaging, and tissue engineering. The challenges and prospects for the future development of biohybrid robots are also presented.

To verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC).It was a block randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into 2 groups at a 1:1 ratio. The patients in the treatment group received conventional therapy including chemotherapy, radiotherapy, targeted therapy and supportive care, and Chinese herbal medicine combined with Quxie Capsule (each capsule of 0.4 g was orally administered at 50 mg/kg, twice daily, day 1-20, in a 30-day course) for 3 months. The patients in the control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to therapy lines, right or left-sided colon, targeted therapy and RAS gene status to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until December 31st, 2018.Median follow-up time was 19.4 months. The median OS was 23.9 months in the treatment group [95% confidence interval (CI) 15.9-28.5] vs. 14.3 months in the control group (95% CI 11.3-21.4, P;0.05). Hazard ratio (95% CI) was 0.55 (0.31-0.95, P=0.040). There were no significant differences between the two groups in PFS (P0.05). In the subgroups of ⩾second-line therapy, non-targeted therapy, RAS gene wild type and left-sided colon, the treatment group showed a significant survival benefit compared with the control group (P;0.05 or P;0.01), respectively.Quxie Capsule can reduce the risk of death and prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733).

Objective To evaluate the association and dose–response pattern between antimalarial drugs and overall and cause specific mortality in SLE patients. Methods Medical records including information on HCQ/chloroquine (CQ) prescription were extracted from Jiangsu Lupus database. The database was designed to collect data from SLE patients that first-hospitalized during 1999–2009 in Jiangsu province, China, and a follow-up for survival status was performed in 2010 and 2015. Cox and restricted cubic spline models were used to estimate the hazard ratio and 95% CI. Results We identified 221 deaths among 2446 SLE patients in total. Compared with non-users, decreased overall mortality was associated with either HCQ or CQ users, with adjusted hazard ratio (95% CI) of 0.49 (0.35, 0.67) and 0.49 (0.27, 0.87), respectively. The association between HCQ/CQ and overall mortality was similar across subgroups, such as patients with comorbidities and organ involvements. Interestingly, both the time and the daily dosage of HCQ/CQ use were related to decreased mortality of SLE in a linear dose–response relationship. In cause specific analyses, HCQ/CQ was inversely associated with death from renal insufficiency and other organ (cardiopulmonary, gastrointestinal and haematological) involvements, with adjusted hazard ratio (95% CI) of 0.23 (0.09, 0.55) and 0.25 (0.10, 0.62), respectively, yet it was not significantly associated with mortality from infection and neuropsychiatric involvements. Conclusion Antimalarial drugs were associated with lower risk of SLE mortality, especially renal insufficiency- and other organ involvement-related death. The protective effects for survival might be augmented by adherence and full dosage of these drugs.

4D printing with a hobbyist FDM printer has enabled a rapid fabrication and self-assembly process for 3D shapes. Researchers have leveraged novel structure design and material techniques to create a wide range of 4D shapes. Meanwhile, 4D printing texture (i.e., shape-changing texture) on objects which could easily augment the haptic sensation, has drawn more attention to this field. In this paper, we introduce 4DTexture, a novel design and fabrication approach that integrates texture design through the 4D printing process. Compared to conventional 3D printing surfaces with texture, which usually requires support structures, 4DTexture can effectively reduce production material, time and the post-process effort after printing. Specifically, 4DTexture prints flat substrates with a customized texture design on its top surfaces, which can easily be triggered and can self-morph to target 3D shapes. Overall, our approach enables the design and fabrication of 3D surfaces with texture and can be leveraged by designers and researchers in the field of personal fabrication.