Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Periplogenin inhibits pyroptosis of fibroblastic synoviocytes in rheumatoid arthritis through the NLRP3/Caspase-1/GSDMD signaling pathway.

Although the pathogenesis of rheumatoid arthritis (RA) remains unclear, an increasing number of studies have confirmed that pyroptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is an important factor affecting the progression of RA. Periplogenin (PPN) is a natural cardiac glycoside; reportedly, it exerts anti-inflammatory and analgesic effects in diseases by inhibiting cell growth and migration. This study aimed to determine the effect of PPN on the growth, migration, and invasion of RA-FLS and the potential mechanism of pyroptosis regulation. We discovered that PPN could inhibit the migration and invasion abilities of RA-FLS and block their growth cycle, down-regulate the secretion and activation of NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18, and reduce the number of pyroptosis. In summary, PPN inhibited pyroptosis, reduced the release of inflammatory factors, and improved RA-FLS inflammation by regulating the NLRP3/Caspase-1/GSDMD signaling pathway.

The causal impact of saturated fatty acids on rheumatoid arthritis: a bidirectional Mendelian randomisation study.

Objective: The causal relationship between saturated fatty acids (SFAs) and rheumatoid arthritis (RA) remains poorly understood. This study aimed to determine whether SFAs are causally related to RA using Mendelian randomisation (MR) analyses. Methods: Genome-wide association study (GWAS) summary data for RA (ukb-d-M13_RHEUMA) and SFAs (met-d-SFA) were obtained from the Integrative Epidemiology Unit OpenGWAS database. A bidirectional MR analysis was performed using a suite of algorithms, namely the MR-Egger, weighted median, simple mode, weighted mode, and inverse-variance weighted (IVW) algorithms, all integrated using the "MR" function. The robustness of the MR findings was further evaluated through sensitivity analyses, including heterogeneity, horizontal pleiotropy, and leave-one-out tests. Results: The IVW algorithm in the forward MR analysis indicated a causal link between SFAs and RA (p = 0.025), identifying SFAs as a risk factor for RA (odds ratio = 1.001). Sensitivity analyses indicated no significant heterogeneity, horizontal pleiotropy, or severe bias, reinforcing the credibility of the forward MR results. However, the reverse MR analysis revealed that RA does not causally affect SFA levels (p = 0.195), and this finding was supported by corresponding sensitivity analyses. Conclusion: The findings of this study substantiate the positive causal effect of SFAs on the incidence of RA through bidirectional MR analysis, thereby offering a consequential direction for future research on the diagnosis and treatment of RA.

Stigmasterol Depresses the Proliferation and Facilitates the Apoptosis of Fibroblast-Like Synoviocytes via the PI3K/AKT Signaling Pathway in Collagen-Induced Arthritis Rats.

Rheumatoid arthritis (RA) is a chronic disease characterized by persistent synovitis and angiogenesis. Its clinical manifestations are synovial hyperplasia and progressive destruction of bone and cartilage, eventually leading to joint deformation and even disability. The healing effect of monomer stigmasterol, the main active ingredient of the Jinwujiangu recipe the Chinese Herbal Compound, on RA has been confirmed in several studies. Fibroblast-like synoviocytes (FLS) are related to the occurrence and development of RA. This study aims to investigate the effects of stigmasterol on FLS cell proliferation and apoptosis, as well as its impact on FLS cell cycle proteins and key genes in the Phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway, providing insights into the development of stigmasterol as an alternative therapeutic drug for RA. We administered 20 g/kg stigmasterol to rats continuously for 5 d to obtain stigmasterol-containing serum, and established rat models of osteoarthritis induced by ossein to obtain FLS. To explore the effects of stigmasterol on the viability, migration, proliferation and apoptosis of collagen-induced arthritis (CIA)-FLS cells, we selected 0% (control), 5% (low concentration), 10% (medium concentration) and 20% (high concentration) drug-containing serum to intervene cells and conducted Cell Counting Kit-8 (CCK-8), Transwell, 5-ethynyl-2' -deoxyuridine (EdU) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) experiments, respectively. The results showed that compared with the control group, low, medium, and high serum significantly inhibited the activity, migration, and proliferation of FLS cells, and promoted their apoptosis, and high serum had the best effect. In addition, we investigated the mechanism of stigmasterol inhibiting FLS proliferation and promoting its apoptosis by qPCR, Western blot, and immunofluorescence assays. The results showed that stigmasterol significantly inhibited the expression of Cyclin D1, cyclin-dependent kinase 4 (CDK4), and Retinoblastoma (Rb), and decreased the expression of key genes kinase insert domain-containing receptor (KDR), PI3K, AKT, phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in the KDR-mediated PI3K/AKT signaling pathway, thus inhibiting the proliferation of FLS and promoting the apoptosis of FLS. It was suggested that stigmasterol may be a potential alternative drug for RA treatment.

Clinical features of acute generalized exanthematous pustulosis caused by hydroxychloroquine in rheumatology patients and exploration of CARD14 gene mutations.

Introduction: Acute generalized exanthematous pustulosis (AGEP) is a rare condition characterized by superficial pustules following drug ingestion or infection. Currently, there is no clear link between rheumatism and AGEP. It has been described that hydroxychloroquine (HCQ) is a rare cause of acute generalized epidermal necrolysis (AGEP). Presently, there are limited studies on HCQ-induced AGEP. We aimed to explore the clinical features and associated gene expression of AGEP induced after HCQ treatment exposure in rheumatology patients. Methods: We assessed patients with HCQ-induced AGEP diagnosed at the Second Affiliated Hospital of Guizhou University of Chinese Medicine between January 1, 2017, and May 1, 2022. We also reviewed similar cases reported in specific databases. Results: The study included five females (mean age, 40.2 years), and the mean time from initiation of HCQ treatment to symptom onset was 12.2 d. All patients received steroids and allergy medications after HCQ discontinuation, and the rash completely resolved within an average of 25.2 d. We performed whole exome sequencing and Sanger validation in our patient sample. CARD14 gene mutations were detected in three patients. Additionally, seven mutation sites were detected. Discussion: HCQ-induced AGEP may have a longer latency period and regression time than AGEP induced by other drugs. Our patients all experienced CARD14 gene mutations. AGEP often resolves with topical therapy and drug discontinuation, although some cases require systemic steroid therapy. In the future, patients with rheumatism should pay attention to the effectiveness of HCQ during treatment and be aware of the associated skin toxicity.

Research on the impact of COVID-19 on the spatiotemporal distribution of carbon dioxide emissions in China.

Since the outbreak of COVID-19 at the end of 2019, the Chinese government has imposed strict control measures on affected cities, which may have impacted the spatial and temporal pattern of carbon dioxide emissions. This paper follows the quantitative analysis method, experimental method, mathematical method, etc., and quantitatively studies the impact of the epidemic on China's carbon emissions. The combination model of ARIMA and BP neural network is used to predict the actual impact of epidemic situation on China's carbon emissions in 2020, and the spatial autocorrelation analysis method is used to analyze the spatial characteristics of China's provincial carbon emissions, which indicate that China's carbon emissions have consistently maintained a growth trend, from 2.05 billion tons in 2005 to 3.89 billion tons in 2019. Furthermore, the growth rate of carbon emissions and the changing trend of the emission intensity are the same, dropping from 12% in 2005 to 3% in 2019. The emission intensity also dropped from 1.1 in 2005 to 0.6 in 2019, indicating that the trend of increasing carbon emissions in northern provinces and Xinjiang changed significantly from 2005 to 2019. The overall carbon emissions of the 30 provinces in 2020 are predicted to be 4.068 billion tons, while the actual energy carbon emissions will be 3.921 billion tons, suggesting that the pandemic significantly reduced carbon emissions. Among affected provinces, carbon emissions from Hubei, Jiangsu, Shandong, Shanghai, and other places changed significantly, from 0.99, 0.25, 0.43, and 76 million tons in 2019 to 0.88, 0.24, 0.42, and 72 million tons in 2020, respectively. The results show a positive spatial correlation between China's provincial carbon emissions; the high-high and bottom-high agglomeration are mainly among the provinces, mainly distributed in North China and East China. Although the pandemic seriously impacts China's carbon emissions, each province's spatial relationship has not changed significantly.

A Systematic Review and Network Meta-Analysis about the Efficacy and Safety of Tripterygium wilfordii Hook F in Rheumatoid Arthritis.

Objective: This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods: We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results: A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion: Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA.

Opportunities for fraudsters: When would profitable milk adulterations go unnoticed by common, standardized FTIR measurements?

Milk is regarded as one of the top food products susceptible to adulteration where its valuable components are specifically identified as high-risk indicators for milk fraud. The current study explores the impact of common milk adulterants on the apparent compositional parameters of milk from the Dutch market as measured by standardized Fourier transform infrared (FTIR) spectroscopy. More precisely, it examines the detectability of these adulterants at various concentration levels using the compositional parameters individually, in a univariate manner, and together in a multivariate approach. In this study we used measured boundaries but also more practical variance-adjusted boundaries to set thresholds for detection of adulteration. The potential economic impact of these adulterations under a milk payment scheme is also evaluated. Twenty-four substances were used to produce various categories of milk adulterations, each at four concentration levels. These substances comprised five protein-rich adulterants, five nitrogen-based adulterants, seven carbohydrate-based adulterants, six preservatives and water, resulting in a set of 360 samples to be analysed. The results showed that the addition of protein-rich adulterants, as well as dicyandiamide and melamine, increased the apparent protein content, while the addition of carbohydrate-based adulterants, whey protein isolate, and skimmed milk powder, increased the apparent lactose content. When considering the compositional parameters univariately, especially protein- and nitrogen-based adulterants did not raise a flag of unusual apparent concentrations at lower concentration levels. Addition of preservatives also went unnoticed. The multivariate approach did not improve the level of detection. Regarding the potential profit of milk adulteration, whey protein and corn starch seem particularly interesting. Combining the artificial inflation of valuable components, the resulting potential profit, and the gaps in detection, it appears that the whey protein isolates deserve particular attention when thinking like a criminal.

Prevalence of Milk Fraud in the Chinese Market and its Relationship with Fraud Vulnerabilities in the Chain.

This study aimed to assess the prevalence of ultra-high-temperature (UHT) processed milk samples suspected of being adulterated on the Chinese market and, subsequently, relate their geographical origin to the earlier determined fraud vulnerability. A total of 52 UHT milk samples purchased from the Chinese market were measured to detect possible anomalies. The milk compositional features were determined by standardized Fourier transform-infrared spectroscopy, and the detection limits for common milk adulterations were investigated. The results showed that twelve of the analysed milk samples (23%) were suspected of having quality or fraud-related issues, while one sample of these was highly suspected of being adulterated (diluted with water). Proportionally, more suspected samples were determined among milks produced in the Central-Northern and Eastern areas of China than in those from the North-Western and North-Eastern areas, while those from the South were in between. Combining the earlier collected results on fraud vulnerability in the Chinese milk chains, it appears that increased fraud prevalence relates to poorer business relationships and lack of adequate managerial controls. Since very few opportunities and motivations differ consistently across high and low-prevalence areas, primarily the improvement of control measures can help to mitigate food fraud in the Chinese milk supply chains.

A combined ultrasonic B-mode and color Doppler system for the classification of breast masses using neural network.

OBJECTIVES: To develop a dual-modal neural network model to characterize ultrasound (US) images of breast masses. MATERIALS AND METHODS: A combined US B-mode and color Doppler neural network model was developed to classify US images of the breast. Three datasets with breast masses were originally detected and interpreted by 20 experienced radiologists according to Breast Imaging-Reporting and Data System (BI-RADS) lexicon ((1) training set, 103212 masses from 45,433 + 12,519 patients. (2) held-out validation set, 2748 masses from 1197 + 395 patients. (3) test set, 605 masses from 337 + 78 patients). The neural network was first trained on training set. Then, the trained model was tested on a held-out validation set to evaluate agreement on BI-RADS category between the model and the radiologists. In addition, the model and a reader study of 10 radiologists were applied to the test set with biopsy-proven results. To evaluate the performance of the model in benign or malignant classifications, the receiver operating characteristic curve, sensitivities, and specificities were compared. RESULTS: The trained dual-modal model showed favorable agreement with the assessment performed by the radiologists (κ = 0.73; 95% confidence interval, 0.71-0.75) in classifying breast masses into four BI-RADS categories in the validation set. For the binary categorization of benign or malignant breast masses in the test set, the dual-modal model achieved the area under the ROC curve (AUC) of 0.982, while the readers scored an AUC of 0.948 in terms of the ROC convex hull. CONCLUSION: The dual-modal model can be used to assess breast masses at a level comparable to that of an experienced radiologist. KEY POINTS: • A neural network model based on ultrasonic imaging can classify breast masses into different Breast Imaging-Reporting and Data System categories according to the probability of malignancy. • A combined ultrasonic B-mode and color Doppler neural network model achieved a high level of agreement with the readings of an experienced radiologist and has the potential to automate the routine characterization of breast masses.

Dairy farming system markers: The correlation of forage and milk fatty acid profiles from organic, pasture and conventional systems in the Netherlands.

The relationships between the fatty acid (FA) composition in forage and milk (F&M) from different dairy systems were investigated. Eighty milk samples and 91 forage samples were collected from 40 farms (19 organic, 11 pasture and 10 conventional) in the Netherlands, during winter and summer. The FA profiles of F&M samples were measured with gas chromatography. The results showed that the F&M of organic farms were significantly differentiated from the F&M of other farms, both in summer and winter. The differences are likely due to the different grazing strategies in summer and different forage composition in winter. The Pearson's correlation results showed the specific relationship between individual FAs in forages and related milk. A PLS-DA model was applied to classify all milks samples, resulting in 87.5% and 83.3% correct classifications of training set and validation set.

[Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis].

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

Adaptive Backstepping Design of a Microgyroscope.

This paper presents a novel algorithm for the design and analysis of an adaptive backstepping controller (ABC) for a microgyroscope. Firstly, Lagrange⁻Maxwell electromechanical equations are established to derive the dynamic model of a z-axis microgyroscope. Secondly, a nonlinear controller as a backstepping design approach is introduced and deployed in order to drive the trajectory tracking errors to converge to zero with asymptotic stability. Meanwhile, an adaptive estimator is developed and implemented with the backstepping controller to update the value of the parameter estimates in the Lyapunov framework in real-time. In addition, the unknown system parameters including the angular velocity may be estimated online if the persistent excitation (PE) requirement is met. A robust compensator is incorporated in the adaptive backstepping algorithm to suppress the parameter variations and external disturbances. Finally, simulation studies are conducted to prove the validity of the proposed ABC scheme with guaranteed asymptotic stability and excellent tracking performance, as well as consistent parameter estimates in the presence of model uncertainties and disturbances.

Detection of three common G6PD gene mutations in Chinese individuals by probe melting curves.

OBJECTIVE: In order to develop and validate an assay for rapid detection of three common G6PD gene mutations in Chinese individuals. METHODS: In this report we design two sets of primers and fluorescently labeled hybridization probes recognizing adjacent sequences in the amplicon; after annealing, the fluorophores were in resonance energy transfer, providing real-time monitoring of the amplication process. At the completion of PCR, fluorescence was monitored as the temperature increased through the Tm of the probe/product duplex, and a characteristic melting profile for each mutation was obtained. By using the fluorescence method and PCR/RE, a total of 57 samples obtained from two groups of G6PD-deficient individuals were studied. RESULT: A rapid method for detection of three common G6PD gene mutations in Chinese individuals by probe melting curves was developed. This method shows 100% accordance with the traditional method. CONCLUSION: This fluorescent melting curve analysis is a simple, rapid, and effective method for clinical diagnosis and screening of G6PD deficiency.