Telitacicept: A novel horizon in targeting autoimmunity and rheumatic diseases.

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.

Crocetin Enhances Temozolomide Efficacy in Glioblastoma Therapy Through Multiple Pathway Suppression.

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells. METHODS: Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 µM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects. RESULTS: Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others. CONCLUSION: Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.

Effect of fly ash and curing temperature on the properties of magnesium phosphate repair mortar.

This article is aimed at discussing the combined effect of mineral admixture and servicing temperature, especially in cold environment, on the properties of magnesium phosphate repair mortar (MPM). The influence mechanism of fly ash content on the microstructure and performance of MPM were firstly investigated, and then the evolution rules in properties of fly ash modified MPM cured at - 20 °C, 0 °C, 20 °C and 40 °C were further revealed. The results show that the incorporation of fly ash has no significant effect on the setting time and fluidity of MPM. When MPM is modified with 10 wt% and 15 wt% fly ash, its mechanical properties, adhesive strength, water resistance, and volume stability are effectively improved. Fly ash reduces the crystallinity and continuity of struvite enriched in hardened MPM, and its particles are embedded among struvite and unreacted MgO. The compressive strength of MPM-10 cured for various ages increases with the elevating of curing temperature, while the flexural strength, interfacial bonding strength, strength retention and linear shrinkage exhibits the opposite laws. When cured at 0 °C and - 20 °C, MPM-10 still has good early strength, water resistance and interfacial bonding properties, which indicates that MPM-10 provides with an ability of emergency repair of cracked components served in cold environments.

Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases.

Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with immune cells being a crucial component of the body's immune system. This review provides an overview and discusses the relationship between ferroptosis, programmed cell death in immune cells, and autoimmune diseases. Additionally, it summarizes the role of various key targets of ferroptosis, such as GPX4 and TFR, in immune cell immune responses. Furthermore, the release of multiple molecules, including damage-associated molecular patterns (DAMPs), following cell death by ferroptosis, is examined, as these molecules further influence the differentiation and function of immune cells, thereby affecting the occurrence and progression of autoimmune diseases. Moreover, immune cells secrete immune factors or their metabolites, which also impact the occurrence of ferroptosis in target organs and tissues involved in autoimmune diseases. Iron chelators, chloroquine and its derivatives, antioxidants, chloroquine derivatives, and calreticulin have been demonstrated to be effective in animal studies for certain autoimmune diseases, exerting anti-inflammatory and immunomodulatory effects. Finally, a brief summary and future perspectives on the research of autoimmune diseases are provided, aiming to guide disease treatment strategies.

Efficacy and safety of culture-expanded mesenchymal stromal cell therapy in the treatment of 4 types of inflammatory arthritis: A systematic review and meta-analysis of 36 randomized controlled trials.

OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.

Exploring the effect of Gouqi Nuzhen Liuhe decoction on the PI3K/mTOR signaling pathway for premature ovarian insufficiency based on system pharmacology.

Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). Conclusion: GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.

Real-Time Cardiac Abnormality Monitoring and Nursing for Patient Using Electrocardiographic Signals.

INTRODUCTION: Cardiovascular disease nursing is a critical clinical application that necessitates real-time monitoring models. Previous models required the use of multi-lead signals and could not be customized as needed. Traditional methods relied on manually designed supervised algorithms, based on empirical experience, to identify waveform abnormalities and classify diseases, and were incapable of monitoring and alerting abnormalities in individual waveforms. METHODS: This research reconstructed the vector model for arbitrary leads using the phase space-time-delay method, enabling the model to arbitrarily combine signals as needed while possessing adaptive denoising capabilities. After employing automatically constructed machine learning algorithms and designing for rapid convergence, the model can identify abnormalities in individual waveforms and classify diseases, as well as detect and alert on abnormal waveforms. RESULT: Effective noise elimination was achieved, obtaining a higher degree of loss function fitting. After utilizing the algorithm in Section 3.1 to remove noise, the signal-to-noise ratio increased by 8.6%. A clipping algorithm was employed to identify waveforms significantly affected by external factors. Subsequently, a network model established by a generative algorithm was utilized. The accuracy for healthy patients reached 99.2%, while the accuracy for APB was 100%, for LBBB 99.32%, for RBBB 99.1%, and for P-wave peak 98.1%. CONCLUSION: By utilizing a three-dimensional model, detailed variations in electrocardiogram signals associated with different diseases can be observed. The clipping algorithm is effective in identifying perturbed and damaged waveforms. Automated neural networks can classify diseases and patient identities to facilitate precision nursing.

Gratitude practice helps undergraduates who experienced an earthquake in China find meaning in life.

This study was conducted following a magnitude 6.8 earthquake that occurred in early September 2022, coinciding with the commencement of a positive psychology course for the affected students. A sample of 479 Chinese undergraduates was recruited for an intervention focused on weekly gratitude practice. Data were collected through an online questionnaire package at 3 time points: the first week of the course (Time 1), the fifth week (Time 2), and the ninth week (Time 3), assessing gratitude, learning engagement, and the meaning of life. Findings revealed that gratitude significantly predicted meaning in life through learning engagement over time. This highlights the significant mediating role of learning engagement in the context of earthquakes and provides insights for positive interventions aimed at facilitating personal growth among emerging adults in higher educational settings, particularly those who have experienced traumatic events such as earthquakes.

Identification of Differentially Expressed Genes and microRNAs in the Gray and White Feather Follicles of Shitou Geese.

The Shitou goose, a highly recognized indigenous breed with gray plumage originating from Chaozhou Raoping in Guangdong Province, China, is renowned for being the largest goose species in the country. Notably, during the pure breeding process of Shitou geese, approximately 2% of the offspring in each generation unexpectedly exhibited white plumage. To better understand the mechanisms underlying white plumage color formation in Shitou geese, we conducted a comparative transcriptome analysis between white and gray feather follicles, aiming to identify key genes and microRNAs that potentially regulate white plumage coloration in this unique goose breed. Our results revealed a number of pigmentation genes, encompassing TYR, TYRP1, EDNRB2, MLANA, SOX10, SLC45A2, GPR143, TRPM1, OCA2, ASIP, KIT, and SLC24A5, which were significantly down-regulated in the white feather follicles of Shitou geese. Among these genes, EDNRB2 and KIT emerged as the most promising candidate genes for white plumage coloration in Shitou geese. Additionally, our analysis also uncovered 46 differentially expressed miRNAs. Of these, miR-144-y may play crucial roles in the regulation of feather pigmentation. Furthermore, the expression of novel-m0086-5p, miR-489-y, miR-223-x, miR-7565-z, and miR-3535-z exhibits a significant negative correlation with the expression of pigmentation genes including TYRP1, EDNRB2, MLANA, SOX10, TRPM1, and KIT, suggesting these miRNAs may indirectly regulate the expression of these genes, thereby influencing feather color. Our findings provide valuable insights into the genetic mechanisms underlying white plumage coloration in Shitou geese and contribute to the broader understanding of avian genetics and coloration research.

The role of CELF family in neurodevelopment and neurodevelopmental disorders.

RNA-binding proteins (RBPs) bind to RNAs and are crucial for regulating RNA splicing, stability, translation, and transport. Among these proteins, the CUGBP Elav-like family (CELF) is a highly conserved group crucial for posttranscriptional regulation by binding to CUG repeats. Comprising CELF1-6, this family exhibits diverse expression patterns and functions. Dysregulation of CELF has been implicated in various neural disorders, encompassing both neurodegenerative and neurodevelopmental conditions, such as Alzheimer's disease and autism. This article aims to provide a comprehensive summary of the CELF family's role in neurodevelopment and neurodevelopmental disorders. Understanding CELF's mechanisms may offer clues for potential therapeutic strategies by regulating their targets in neurodevelopmental disorders.

Social support predicted subsequent subjective well-being during the COVID-19 pandemic: a prospective study.

BACKGROUND: Subjective well-being (SWB) is associated with social support in cross-sectional studies. However, it remains unclear whether and how social support predicts SWB longitudinally, especially during the COVID-19 contingency. METHODS: By adopting a prospective design, the current work addressed this research question in a sample of 594 participants from the U.K. The data were collected via the online platform, Prolific, at two time points (June, 2020 and August, 2021) with a 14-month interval. Descriptive analysis and a moderated mediation model were conducted to test the proposed hypotheses. RESULTS: Baseline social support was a significant predictor of subjective well-being (SWB) 14 months later, even after controlling for baseline SWB and other covariates such as personality traits. Additionally, affect balance (i.e., the affective component of SWB) fully mediated the link between baseline social support and subsequent life satisfaction (i.e., the cognitive component of SWB). Moreover, household income moderated this relationship, indicating a stronger mediation for individuals with lower monthly household income. CONCLUSION: The present work sheds light on the underlying mechanism and boundary condition of the association between social support and different components of SWB during the COVID-19 pandemic.

Research advances on molecular mechanism and natural product therapy of iron metabolism in heart failure.

The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.

Precision Identification of Locally Advanced Rectal Cancer in Denoised CT Scans Using EfficientNet and Voting System Algorithms.

BACKGROUND AND OBJECTIVE: Local advanced rectal cancer (LARC) poses significant treatment challenges due to its location and high recurrence rates. Accurate early detection is vital for treatment planning. With magnetic resonance imaging (MRI) being resource-intensive, this study explores using artificial intelligence (AI) to interpret computed tomography (CT) scans as an alternative, providing a quicker, more accessible diagnostic tool for LARC. METHODS: In this retrospective study, CT images of 1070 T3-4 rectal cancer patients from 2010 to 2022 were analyzed. AI models, trained on 739 cases, were validated using two test sets of 134 and 197 cases. By utilizing techniques such as nonlocal mean filtering, dynamic histogram equalization, and the EfficientNetB0 algorithm, we identified images featuring characteristics of a positive circumferential resection margin (CRM) for the diagnosis of locally advanced rectal cancer (LARC). Importantly, this study employs an innovative approach by using both hard and soft voting systems in the second stage to ascertain the LARC status of cases, thus emphasizing the novelty of the soft voting system for improved case identification accuracy. The local recurrence rates and overall survival of the cases predicted by our model were assessed to underscore its clinical value. RESULTS: The AI model exhibited high accuracy in identifying CRM-positive images, achieving an area under the curve (AUC) of 0.89 in the first test set and 0.86 in the second. In a patient-based analysis, the model reached AUCs of 0.84 and 0.79 using a hard voting system. Employing a soft voting system, the model attained AUCs of 0.93 and 0.88, respectively. Notably, AI-identified LARC cases exhibited a significantly higher five-year local recurrence rate and displayed a trend towards increased mortality across various thresholds. Furthermore, the model's capability to predict adverse clinical outcomes was superior to those of traditional assessments. CONCLUSION: AI can precisely identify CRM-positive LARC cases from CT images, signaling an increased local recurrence and mortality rate. Our study presents a swifter and more reliable method for detecting LARC compared to traditional CT or MRI techniques.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Variable Time-Step Physics Engine with Continuous Compliance Contact Model for Optimal Robotic Grinding Trajectory Planning.

In the transition from virtual environments to real-world applications, the role of physics engines is crucial for accurately emulating and representing systems. To address the prevalent issue of inaccurate simulations, this paper introduces a novel physics engine uniquely designed with a compliant contact model designed for robotic grinding. It features continuous and variable time-step simulations, emphasizing accurate contact force calculations during object collision. Firstly, the engine derives dynamic equations considering spring stiffness, damping coefficients, coefficients of restitution, and external forces. This facilitates the effective determination of dynamic parameters such as contact force, acceleration, velocity, and position throughout penetration processes continuously. Secondly, the approach utilizes effective inertia in developing the contact model, which is designed for multi-jointed robots through pose transformation. The proposed physics engine effectively captures energy conversion in scenarios with convex contact surface shapes through the application of spring dampers during collisions. Finally, the reliability of the contact solver in the simulation was verified through bouncing ball experiments and robotic grinding experiments under different coefficients of restitution. These experiments effectively recorded the continuous variations in parameters, such as contact force, verifying the integral stability of the system. In summary, this article advances physics engine technology beyond current geometrically constrained contact solutions, enhancing the accuracy of simulations and modeling in virtual environments. This is particularly significant in scenarios wherein there are constant changes in the outside world, such as robotic grinding tasks.

Prediction of jaw opening function after mandibular reconstruction using subject-specific musculoskeletal modelling.

BACKGROUND: Mandibular reconstruction patients often suffer abnormalities in the mandibular kinematics. In silico simulations, such as musculoskeletal modelling, can be used to predict post-operative mandibular kinematics. It is important to validate the mandibular musculoskeletal model and analyse the factors influencing its accuracy. OBJECTIVES: To investigate the jaw opening-closing movements after mandibular reconstruction, as predicted by the subject-specific musculoskeletal model, and the factors influencing its accuracy. METHODS: Ten mandibular reconstruction patients were enrolled in this study. Cone-beam computed tomography images, mandibular movements, and surface electromyogram signals were recorded preoperatively. A subject-specific mandibular musculoskeletal model was established to predict surgical outcomes using patient-averaged muscle parameter changes as model inputs. Jaw bone geometry was replaced by surgical planning results, and the muscle insertion sites were registered based on the non-rigid iterative closest point method. The predicted jaw kinematic data were validated based on 6-month post-operative measurements. Correlations between the prediction accuracy and patient characteristics (age, pathology and surgical scope) were further analysed. RESULTS: The root mean square error (RMSE) for lower incisor displacement was 31.4%, and the error for peak magnitude of jaw opening was 4.9 mm. Age, post-operative infection and radiotherapy influenced the prediction accuracy. The amount of masseter detachment showed little correlation with jaw opening. CONCLUSION: The mandibular musculoskeletal model successfully predicted short-range jaw opening functions after mandibular reconstruction. It provides a novel surgical planning method to predict the risk of developing trismus.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Breakthrough SARS-CoV-2 infection and disease flares in patients with rheumatoid arthritis: result from COVAD e-survey study.

COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. This study aimed to identify factors associated with breakthrough infection (BIs) and disease flares in patients with RA following COVID-19. We analysed data from RA patients who participated in the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities, pharmacologic treatment and details regarding disease flares were extracted from the COVAD database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. The analysis comprised 1928 patients with RA who participated in the COVAD study. Younger age, Caucasian ethnicity, comorbidities with obstructive chronic pulmonary disease and asthma were associated with COVID-19 breakthrough infection. Moreover, younger age (odds ratio (OR): 0.98, 95% CI 0.96-0.99, p < 0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI 1.12-12.94, p = 0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56-4.17, p < 0.001), poor global physical health (OR: 1.07, 95% CI 1.00-1.15, p = 0.044) and mental health (OR: 0.91, 95% CI 0.87-0.95, p < 0.001) were independent factors associated disease flares in patients with RA. Our study highlights the impact of socio-demographic factors, clinical characteristics and mental health on disease flares in patients with RA. These insights may help determine relevant strategies to proactively manage RA patients at risk of flares.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

General anesthesia with local infiltration reduces urine retention rate and prolongs analgesic effect than spinal anesthesia for hemorrhoidectomy.

Introduction: Postoperative pain and complications pose significant challenges following a hemorrhoidectomy. Attaining effective anesthesia with minimal complications is crucial. The ideal anesthesia method for ambulatory hemorrhoidectomy remains uncertain. This study aimed to investigate whether the combination of general anesthesia plus local infiltration (GAL) is associated with lower complications and reduced pain compared to spinal anesthesia (SA) in the context of hemorrhoidectomy. Methods: This retrospective single-center cohort study, conducted in a tertiary medical center in East Asia, evaluated excisional hemorrhoidectomies performed between January 1, 2017, and March 31, 2023, utilizing GAL or SA. Data on the six most common complications-pain, constipation, acute urine retention (AUR), bleeding, nausea, and headache-were extracted from medical records. A total of 550 hemorrhoidectomies were included: 220 in the GAL group and 330 in the SA group. Patient characteristics were comparable between the two groups. Results: The AUR rate was significantly lower in the GAL group compared to the SA group (15.5% vs. 32.1%, P < 0.001). Although the proportion of pain scores ≥4 did not differ significantly between the GAL and SA groups (36.2% vs. 39.8%, P = 0.429), the pain score curve indicated a stable trend. Overall, the GAL group exhibited a lower rate of adverse effects (56.9% vs. 67.4%, P = 0.023). There were no significant differences in the rates of other complications and emergency department readmission between the GAL and SA groups. Discussion: GAL emerges as a favorable choice for anesthesia in hemorrhoidectomy, demonstrating a lower incidence of urine retention and a prolonged analgesic effect in multiple hemorrhoidectomies. These findings support the conclusion that GAL represents an optimal anesthetic method for enhancing the postoperative experience in patients undergoing hemorrhoidectomy.