Analysis of Imprecision for Internal Quality Control of Newborn Screening by Tandem Mass Spectrometry in China, 2015 - 2021.

BACKGROUND: This study aimed to assess the performance of the newborn screening laboratories in China through retrospective analysis of the coefficient of variation (CV) of the internal quality control (IQC) data in the national tandem mass spectrometry screening for inherited metabolic disorders in newborns. METHODS: From 2015 to 2021, the IQC data of amino acid and acylcarnitine test were collected twice each year. CVmonthly in-control was calculated by excluding outliers for the current month and its discrete distribution and changes in trend were comprehensively evaluated for both normal and high concentration levels. The proportion of laboratories meeting both 1/3 and 1/4 quality criteria of the total error allowable (TEa), based on the CVmonthly in-control for each testing item, was calculated. RESULTS: The analysis of CVmonthly in-control for the two concentration levels for the amino acids and acylcarnitine parameters showed that CVmonthly in-control for the normal concentration levels were more discrete before 2018, while CVmonthly in-control for the high concentration levels were less discrete than the normal concentration levels, but there were relatively more outliers. More than 80% of laboratories were able to meet the 1/3 TEa standard for each test at the high concentration level, while the pass rate for the 1/4 TEa standard was significantly lower than 80% (except for C2). CONCLUSIONS: According to the current status of testing in China, it is recommended to use 1/3TEa as the imprecision level standard; for laboratories with relatively high precision, the 1/4TEa standard can be used.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

BACKGROUND: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice. METHODS: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline. RESULTS: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory. CONCLUSIONS: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

The Association Between Rumination and Craving in Chinese Methamphetamine-Dependent Patients: The Masking Effect of Depression.

BACKGROUND: Craving is a core feature of addiction. Rumination and depression play a crucial role in the process of methamphetamine addiction. The aim of this study was to examine the relationship between rumination, depression and craving in methamphetamine patients, which has not been explored yet. METHODS: A total of 778 patients with methamphetamine user disorder (MUD) at the Xinhua Drug Rehabilitation Center, located in Mianyang City, Sichuan Province, China. We used a set of self-administered questionnaires that included socio-demographic, detailed drug use history, rumination, depression and craving information. The Rumination Response Scale (RRS) was used to measure rumination, the Beck Depression Inventory (BDI) to measure depression and the Visual Analogue Scale (VAS) to measure craving. RESULTS: There was a significant positive correlation between rumination and craving, or depression, and between depression and craving. Furthermore, depression mediated between rumination and craving, with a mediation effect of 160%. CONCLUSIONS: Our findings suggest that there is a close interrelationship between rumination, craving and depression in MUD patients, and that depression may play a mediating role between rumination and craving.

This is the first study to investigate the relationship between rumination and craving during withdrawal in methamphetamine dependent patients and the mediating role of depression.Among methamphetamine patients, it was found that reflection was positively correlated with rumination and depression, depression and craving, rumination and craving, and depression plays the mediating role between rumination and craving.These findings suggest that interventions to reduce depression and rumination may also be effective for withdrawal and relapse reduction in methamphetamine patients, providing further rationale for the treatment of methamphetamine patients.

Facilitated Unidirectional Electron Transmission by Ru Nano Particulars Distribution on MXene Mo2C@g-C3N4 Heterostructures for Enhanced Photocatalytic H2 Evolution.

Precious metals exhibit promising potential for the hydrogen evolution reaction (HER), but their limited abundance restricts widespread utilization. Loading precious metal nanoparticles (NPs) on 2D/2D heterojunctions has garnered considerable interest since it saves precious metal consumption and facilitates unidirectional electron transmission from semiconductors to active sites. In this study, Ru NPs loaded on MXenes Mo2C by an in-site simple strategy and then formed 2D/2D heterojunctions with 2D g-C3N4 (CN) via electrostatic self-assembly were used to enhance photocatalytic H2 evolution. Evident from energy band structure analyses such as UV-vis and TRPL, trace amounts of Ru NPs as active sites significantly improve the efficiency of the hydrogen evolution reaction. More interestingly, MXene Mo2C, as substrates for supporting Ru NPs, enriches photoexcited electrons from CN, thereby enhancing the unidirectional electron transmission. As a result, the combination of Ru-Mo2C and CN constructs a composite heterojunction (Ru-Mo2C@CN) that shows an improved H2 production rate at 1776.4 µmol∙g-1∙h-1 (AQE 3.58% at 400 nm), which is facilitated by the unidirectional photogenerated electron transmission from the valence band on CN to the active sites on Ru (CN→Mo2C→Ru). The study offers fresh perspectives on accelerated unidirectional photogenerated electron transmission and saved precious metal usage in photocatalytic systems.

HiFine: integrating Hi-C-based and shotgun-based methods to refine binning of metagenomic contigs.

MOTIVATION: Metagenomic binning aims to retrieve microbial genomes directly from ecosystems by clustering metagenomic contigs assembled from short reads into draft genomic bins. Traditional shotgun-based binning methods depend on the contigs' composition and abundance profiles and are impaired by the paucity of enough samples to construct reliable co-abundance profiles. When applied to a single sample, shotgun-based binning methods struggle to distinguish closely related species only using composition information. As an alternative binning approach, Hi-C-based binning employs metagenomic Hi-C technique to measure the proximity contacts between metagenomic fragments. However, spurious inter-species Hi-C contacts inevitably generated by incorrect ligations of DNA fragments between species link the contigs from varying genomes, weakening the purity of final draft genomic bins. Therefore, it is imperative to develop a binning pipeline to overcome the shortcomings of both types of binning methods on a single sample. RESULTS: We develop HiFine, a novel binning pipeline to refine the binning results of metagenomic contigs by integrating both Hi-C-based and shotgun-based binning tools. HiFine designs a strategy of fragmentation for the original bin sets derived from the Hi-C-based and shotgun-based binning methods, which considerably increases the purity of initial bins, followed by merging fragmented bins and recruiting unbinned contigs. We demonstrate that HiFine significantly improves the existing binning results of both types of binning methods and achieves better performance in constructing species genomes on publicly available datasets. To the best of our knowledge, HiFine is the first pipeline to integrate different types of tools for the binning of metagenomic contigs. AVAILABILITY AND IMPLEMENTATION: HiFine is available at https://github.com/dyxstat/HiFine. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Problem-Dependent Power of Quantum Neural Networks on Multiclass Classification.

Quantum neural networks (QNNs) have become an important tool for understanding the physical world, but their advantages and limitations are not fully understood. Some QNNs with specific encoding methods can be efficiently simulated by classical surrogates, while others with quantum memory may perform better than classical classifiers. Here we systematically investigate the problem-dependent power of quantum neural classifiers (QCs) on multiclass classification tasks. Through the analysis of expected risk, a measure that weighs the training loss and the generalization error of a classifier jointly, we identify two key findings: first, the training loss dominates the power rather than the generalization ability; second, QCs undergo a U-shaped risk curve, in contrast to the double-descent risk curve of deep neural classifiers. We also reveal the intrinsic connection between optimal QCs and the Helstrom bound and the equiangular tight frame. Using these findings, we propose a method that exploits loss dynamics of QCs to estimate the optimal hyperparameter settings yielding the minimal risk. Numerical results demonstrate the effectiveness of our approach to explain the superiority of QCs over multilayer Perceptron on parity datasets and their limitations over convolutional neural networks on image datasets. Our work sheds light on the problem-dependent power of QNNs and offers a practical tool for evaluating their potential merit.

Association between malnutrition and surgical site wound infection among spinal surgery patients: A meta-analysis.

A surgical site infection (SSI) is one of the most common complications of spinal surgery. Malnutrition has also been linked to SSI after other surgical procedures. However, whether malnutrition is a risk factor for SSI after spinal surgery remains controversial. Therefore, we performed a meta-analysis to comprehensively evaluate the relationship between malnutrition and SSI. Relevant studies of the correlation between malnutrition and SSI were retrieved from the Cochrane Library, EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure and Wanfang Data from database inception to 21 May 2023. Two reviewers independently assessed the included studies, and a meta-analysis was performed using STATA 17.0 software. A total of 24 articles with 179 388 patients were included: 3919 and 175 469 cases comprised the SSI and control groups, respectively. The meta-analysis results showed that malnutrition significantly increased the SSI incidence (odds ratio, 1.811; 95% confidence interval, 1.512-2.111; p < 0.001). These results suggest that patients with malnutrition are at higher risk for SSI after surgery. However, because of significant differences in sample sizes among studies, and because some studies had limitations to their methodological quality, further validation of these results by additional high-quality studies with larger sample sizes is necessary.

Efficient Measure for the Expressivity of Variational Quantum Algorithms.

The superiority of variational quantum algorithms (VQAs) such as quantum neural networks (QNNs) and variational quantum eigensolvers (VQEs) heavily depends on the expressivity of the employed Ansätze. Namely, a simple Ansatz is insufficient to capture the optimal solution, while an intricate Ansatz leads to the hardness of trainability. Despite its fundamental importance, an effective strategy of measuring the expressivity of VQAs remains largely unknown. Here, we exploit an advanced tool in statistical learning theory, i.e., covering number, to study the expressivity of VQAs. Particularly, we first exhibit how the expressivity of VQAs with an arbitrary Ansätze is upper bounded by the number of quantum gates and the measurement observable. We next explore the expressivity of VQAs on near-term quantum chips, where the system noise is considered. We observe an exponential decay of the expressivity with increasing circuit depth. We also utilize the achieved expressivity to analyze the generalization of QNNs and the accuracy of VQE. We numerically verify our theory employing VQAs with different levels of expressivity. Our Letter opens the avenue for quantitative understanding of the expressivity of VQAs.

Efficient Bipartite Entanglement Detection Scheme with a Quantum Adversarial Solver.

The recognition of entanglement states is a notoriously difficult problem when no prior information is available. Here, we propose an efficient quantum adversarial bipartite entanglement detection scheme to address this issue. Our proposal reformulates the bipartite entanglement detection as a two-player zero-sum game completed by parameterized quantum circuits, where a two-outcome measurement can be used to query a classical binary result about whether the input state is bipartite entangled or not. In principle, for an N-qubit quantum state, the runtime complexity of our proposal is O(poly(N)T) with T being the number of iterations. We experimentally implement our protocol on a linear optical network and exhibit its effectiveness to accomplish the bipartite entanglement detection for 5-qubit quantum pure states and 2-qubit quantum mixed states. Our work paves the way for using near-term quantum machines to tackle entanglement detection on multipartite entangled quantum systems.

Microbial production of riboflavin: Biotechnological advances and perspectives.

Riboflavin is an essential nutrient for humans and animals, and its derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are cofactors in the cells. Therefore, riboflavin and its derivatives are widely used in the food, pharmaceutical, nutraceutical and cosmetic industries. Advances in biotechnology have led to a complete shift in the commercial production of riboflavin from chemical synthesis to microbial fermentation. In this review, we provide a comprehensive review of biotechnologies that enhance riboflavin production in microorganisms, as well as representative examples. Firstly, the synthesis pathways and metabolic regulatory processes of riboflavin in microorganisms; and the current strategies and methods of metabolic engineering for riboflavin production are systematically summarized and compared. Secondly, the using of systematic metabolic engineering strategies to enhance riboflavin production is discussed, including laboratory evolution, histological analysis and high-throughput screening. Finally, the challenges for efficient microbial production of riboflavin and the strategies to overcome these challenges are prospected.

Angiogenic and Arthritogenic Properties of the Soluble Form of CD13.

Aminopeptidase N/CD13 is expressed by fibroblast-like synoviocytes (FLS) and monocytes (MNs) in inflamed human synovial tissue (ST). This study examined the role of soluble CD13 (sCD13) in angiogenesis, MN migration, phosphorylation of signaling molecules, and induction of arthritis. The contribution of sCD13 was examined in angiogenesis and MN migration using sCD13 and CD13-depleted rheumatoid arthritis (RA) synovial fluids (SFs). An enzymatically inactive mutant CD13 and intact wild-type (WT) CD13 were used to determine whether its enzymatic activity contributes to the arthritis-related functions. CD13-induced phosphorylation of signaling molecules was determined by Western blotting. The effect of sCD13 on cytokine secretion from RA ST and RA FLS was evaluated. sCD13 was injected into C57BL/6 mouse knees to assess its arthritogenicity. sCD13 induced angiogenesis and was a potent chemoattractant for MNs and U937 cells. Inhibitors of Erk1/2, Src, NF-κB, Jnk, and pertussis toxin, a G protein-coupled receptor inhibitor, decreased sCD13-stimulated chemotaxis. CD13-depleted RA SF induced significantly less MN migration than sham-depleted SF, and addition of mutant or WT CD13 to CD13-depleted RA SF equally restored MN migration. sCD13 and recombinant WT or mutant CD13 had similar effects on signaling molecule phosphorylation, indicating that the enzymatic activity of CD13 had no role in these functions. CD13 increased the expression of proinflammatory cytokines by RA FLS, and a CD13 neutralizing Ab inhibited cytokine secretion from RA ST organ culture. Mouse knee joints injected with CD13 exhibited increased circumference and proinflammatory mediator expression. These data support the concept that sCD13 plays a pivotal role in RA and acute inflammatory arthritis.

Transient absorption measurements of interlayer charge transfer in a WS2/GeS van der Waals heterostructure.

We introduce germanium sulfide (GeS) as a new layered material for the fabrication of two-dimensional van der Waals materials and heterostructures. Heterostructures of WS2/GeS were fabricated using mechanical exfoliation and dry transfer techniques. Significant photoluminescence quenching of WS2 in the heterostructures indicates efficient charge transfer. Transient absorption measurements were performed to study the dynamics of charge transfer. The results show that the heterostructure forms a type-II band alignment with the conduction band minimum and valence band maximum located in the WS2 and GeS layers, respectively. The ultrafast hole transfer from WS2 to GeS is confirmed by the faster decay of the lower peak value of the differential reflection signal in the heterostructure sample, in comparison to the WS2 monolayer. These results introduce GeS as a promising semiconductor material for developing new novel heterostructures.

Analysis of External Quality Assessment of Maternal Serum Prenatal Screening for Down Syndrome in the First Trimester in China.

BACKGROUND: We analyzed the 2019 external quality assessment (EQA) results to evaluate the analytical performance of maternal serum prenatal screening for Down Syndrome (DS) in the first trimester in China. METHODS: In each round, five lyophilized EQA samples with detailed clinical information were distributed to participants and used to test the concentration of human chorionic gonadotropin free beta subunits (free ß-HCG) and pregnancy-associated plasma protein-A (PAPP-A) to calculate the risk value of DS. The robust coefficient of variability (CV) was calculated or test results for free ß-HCG and PAPP-A using analytes and major measurement platforms. For DS risk values, the robust CV was calculated using a professional calculation platform. Failed EQA results were analyzed using serum marker testing results and DS risk values. RESULTS: EQA results were collected from 242 laboratories in round 1 and 239 laboratories in round 2. Total acceptable rates of testing results for free ß-HCG and PAPP-A ranged from 95.04% to 97.91%. Overall acceptable rates of DS risk values ranged from 97.52% to 97.90%. The proportion of laboratories exhibiting satisfactory performance was higher in round 2 than in round 1 for serum marker testing results and DS risk values. The robust CV for risk values for each sample were significantly higher than those of serum markers. Three EQA result failure types were found, including result reporting errors, serum marker concentration testing errors, and DS risk calculation errors. CONCLUSIONS: The analytical performance of maternal serum prenatal screening for DS in the first trimester in China can be improved further.

Quality assessment of interpretative commenting and competency comparison of comment providers in China.

Background This study aimed to evaluate the ability of comment providers who were responsible for interpreting results in clinical laboratories in China and to improve the quality of interpretative comments. Methods Basic information and interpretative comments for five cases of 1912 routine chemistry External Quality Assessment (EQA) participant laboratories were collected by web-based EQA system in May 2018. EQA organizers assigned scores to each key phrase of comments based on predetermined marking scale and calculated total scores for each participant's answer. Final scores and ranking were calculated according to scores of cases. Finally, we comprehensively analyzed the type of hospital and the professional title of participants. Results In total, 772 clinical laboratories, 1472 participants, from different Chinese provinces submitted interpretative comments. Median scores, interquartile ranges and score ranges of the five cases were 13 (11-15, 1-20), 13 (10-16, 0-20), 15 (12-17, 0-21), 7 (5-9, -2 to 14) and 12 (10-13, -2 to 18). The final scores and ranking of participants that came from tertiary hospitals were higher than those from secondary and other hospitals; however, there were no significant differences (0.774). When grouped by professional title, we found that although no significant variability existed among senior, intermediate, junior and others (0.699), it existed between laboratory physicians and technicians, as the median final scores of the former were higher than the latter. Conclusions Practice and quality of interpretative comments are indeed different among different laboratories and participants in China. Laboratories should train and assess the interpretative ability of personnel. EQA organizers should also improve the scoring method and establish peer assessors team through this survey.

Analysis and evaluation of the external quality assessment results of quality indicators in laboratory medicine all over China from 2015 to 2018.

Background This study aimed to comprehensively evaluate laboratory quality in China and explore factors affecting laboratory errors through analyzing the external quality assessment (EQA) results of quality indicators (QIs). Methods According to model 3 (interpretive) of the proficiency testing scheme, the National Center for Clinical Laboratories of China (CNCCL) developed a questionnaire for 15 QIs. Clinical laboratories from different provinces of China participated in the EQA program of QIs annually and submitted data via an online reporting system named Clinet-EQA. The results of QIs were expressed in percentage and sigma value or minute. Three levels of quality specifications (QSs) were defined based on percentile values. Furthermore, the QIs were analyzed by disciplines, hospital scales and information construction levels of participant laboratories. Results A total of 3450 laboratories nationwide continuously attended the EQA program and submitted complete data from 2015 to 2018. The performance of most QIs has improved year by year. QIs in post-analytical gained the best performance with sigma values that varied from 5.3σ to 6.0σ. The comparison of results among different disciplines showed significant differences for five QIs. More than half of QIs had statistical differences among different hospital scales measured by hospital grades and number of hospital beds. The performance of nine QIs were influenced by information construction levels of participant laboratories. Conclusions The overall laboratory quality in China has improved since the initiation of EQA program for QIs, but the performance of some QIs was still unsatisfactory. Therefore, laboratories should make efforts for continuous quality improvement based on information provided by QSs.

External Quality Assessment Program for Newborn Screening of Amino Acids in China.

BACKGROUND: To analyze the 2017 external quality assessment (EQA) results of newborn screening by MS/MS of amino acids by Chinese National Center for Clinical Laboratories, this study aimed to reflect the performance of clinical laboratories. METHODS: Five dried blood spots were distributed to participants every round. Satisfactory performance was defined as scores more than 80 of acceptable results within the evaluation criterion. The robust coefficient of variability (RCV) of each sample was calculated by measurement systems. The chi-square () test was used to compare the correct recognition rates. RESULTS: EQA results were collected from 150 laboratories for Ala, Val, Arg, Leu, Met, Phe, Tyr, Cit. The overall acceptable rates of the qualitative results were 87.42%, 92.72%, 73.33%, 94.04%, 92.72%, 94.70%, 92.72%, 94.04%, respectively, and the proportion of acceptable quantitative results were 76.51 %, 91.95%, 78.38 %, 92.62%, 93.29%, 93.29%, 94.63%, 91.28%, respectively. There were significant differences in the rates of acceptable quantitative results among different items and between four methods. CONCLUSIONS: Most of the participant laboratories had satisfactory performance for the quantitative results in this EQA scheme. But for qualitative assessment, the laboratory should re-evaluate and validate their reference intervals on a regular basis to improve the consistency of clinical assessment.

External Quality Assessment Program for Newborn Screening of Acylcarnitine in China, 2018.

BACKGROUND: The aim of this study was to analyze the 2018 external quality assessment (EQA) results of newborn screening by MS/MS of acylcarnitine by Chinese National Center for Clinical Laboratories and to determine the performance of clinical laboratories. METHODS: Five dried blood spots were distributed to participants every round. Satisfactory performance was defined as scores more than 80 of acceptable results within the evaluation criterion. The robust coefficient of variability (RCV) of each sample was calculated by measurement systems. The chi-square (2) test was used to compare the correct recognition rates. RESULTS: EQA results were collected from 150 laboratories for 15 different acylcarnitines between C0 - C18. The overall acceptable rates of the qualitative results were between 81.21% and 96.67%, and the proportion of acceptable quantitative results were between 78.38% and 93.24%. There were significant differences in the rates of acceptable quantitative results among different items and between the four methods. CONCLUSIONS: Most of the participant laboratories had satisfactory performance for the quantitative results in this EQA scheme. But for qualitative assessment, a laboratory should re-evaluate and validate their reference intervals on a regular basis to improve the consistency of clinical assessment.

BBS Posts Time Series Analysis based on Sample Entropy and Deep Neural Networks.

The modeling and forecasting of BBS (Bulletin Board System) posts time series is crucial for government agencies, corporations and website operators to monitor public opinion. Accurate prediction of the number of BBS posts will assist government agencies or corporations in making timely decisions and estimating the future number of BBS posts will help website operators to allocate resources to deal with the possible hot events pressure. By combining sample entropy (SampEn) and deep neural networks (DNN), an approach (SampEn-DNN) is proposed for BBS posts time series modeling and forecasting. The main idea of SampEn-DNN is to utilize SampEn to decide the input vectors of DNN with smallest complexity, and DNN to enhance the prediction performance of time series. Selecting Tianya Zatan new posts as the data source, the performances of SampEn-DNN were compared with auto-regressive integrated moving average (ARIMA), seasonal ARIMA, polynomial regression, neural networks, etc. approaches for prediction of the daily number of new posts. From the experimental results, it can be found that the proposed approach SampEn-DNN outperforms the state-of-the-art approaches for BBS posts time series modeling and forecasting.

Depleting the carboxy-terminus of human Wnt5a attenuates collagen-induced arthritis in DBA/1 mice.

Wnt5a signalling plays pathological roles in synovial inflammation and bone destruction. In the present study, we designed four human Wnt5a-based DNA recombinants and detected their effects on immunogenicity and anti-rheumatism in a collagen-induced arthritis (CIA) model. Histomorphometry and micro-CT scanning showed that the phWnt5a-NL was superior to other recombinants because it resulted in decreased severity of arthritis, histopathological scores of synovial inflammation and bone erosion in CIA mice. In addition, ELISA and TRAP staining showed that the phWnt5a-NL-immunized CIA mice had reductions in the serum concentrations of the rheumatoid-associated cytokines IL-1ß and RANKL and in osteoclastogenesis. Furthermore, flow cytometry showed that the phWnt5a-NL treatment increased the percentage of Treg cells. Finally, western blotting analysis showed that the phWnt5a-NL-immunization interrupted ß-catenin and JNK expression in osteoclast precursors derived from the CIA mice. The results suggest that depleting the carboxy-terminus in hWnt5a-based DNA recombinants may be beneficial for the treatment of chronic inflammatory disorders involving bone resorption.