Background: Multisite chronic pain (MCP) is a debilitating condition disproportionately affecting females, yet its underlying biological basis, particularly the connection to brain structure and the specific role of genetic factors, remains incompletely understood. Methods: This study delves into the genetic correlation between MCP in females and cerebral cortical morphology, specifically concentrating on cortical thickness (CT) and surface area (SA). Leveraging genome-wide association study (GWAS) data, the investigation establishes significant genetic correlations between female MCP and diverse cerebral cortical regions. Results: The outcomes underscored that diminished CT in the frontal pole, increased CT in the rostral middle frontal cortex, and reduced SA in the superior frontal cortex exhibited nominal associations with increased susceptibility to MCP in females (P < 0.05). Conversely, MCP susceptibility demonstrated a nominal causal association with reduced CT in the parahippocampal gyrus and postcentral gyrus. Gene enrichment analysis suggests potential correlations between these genetic loci and biological pathways related to body mass index and pain phenotypes. Conclusions: This study provided exploratory evidence of potential shared genetic pathways influencing both MCP susceptibility and cerebral cortex structure. The results suggested that alterations in brain morphology in females may have a bidirectional relationship with susceptibility to chronic pain.

Systemic Lupus Erythematosus (SLE) is a complex autoimmune condition, fundamentally characterized by the loss of self-tolerance. This breakdown leads to the generation of autoantibodies and widespread inflammation that compromises multiple organs. A significant clinical challenge in SLE management is the lack of effective options for refractory disease, driving the pursuit of innovative treatments. Among these, mesenchymal stromal/stem cells (MSCs) have garnered significant attention due to their potent immunomodulatory and tissue-repair capabilities, highlighting their potential as a viable therapy. This review critically assesses the potential of MSCs in reconciling the unmet need for effective SLE therapies by examining their immunomodulatory mechanisms, clinical efficacy, and safety. MSCs reestablish immune tolerance through coordinated interactions with T and B cells, macrophages, and dendritic cells, predominantly facilitated by soluble factor secretion and extracellular vesicle release. In severe SLE, allogeneic MSC transplantation has demonstrated a capacity to induce durable remission, restore organ function, and improve survival rates, coupled with a reassuring safety profile. However, the field must still address issues of product standardization and long-term safety evaluation. Next-generation solutions-featuring engineered MSCs, iPSC-MSCs products, and vesicle-based therapies-hold the potential to usher in a new era of personalized SLE treatment. The conduct of large-scale randomized controlled trials is now imperative to definitively establish therapeutic efficacy and optimize clinical protocols.

OBJECTIVES:The subdivisions of the anterior cingulate cortex (ACC) are involved in distinct functions in the processing of chronic pain and regulation of emotions. However, the specific impact of each ACC subdivision on fibromyalgia (FM) remains unclear. This study aimed to systematically investigate the abnormal resting-state functional connectivity (rsFC) patterns between the ACC (and its subregions) and other chronic-pain-related limbic cortices and subcortical nuclei in patients with FM. METHODS:Resting-state functional magnetic resonance imaging (fMRI) was conducted in 31 patients diagnosed with fibromyalgia (FM) and 32 demographically matched healthy controls (HCs). Using subdivisions of the anterior cingulate cortex (ACC) as regions of interest, we employed a seed-based resting-state functional connectivity (rsFC) approach to identify alterations in connectivity between limbic cortex and subcortical nuclei. A two-sample t-test was applied to compare functional connectivity differences between the two groups. Additionally, Pearson correlation analysis was performed to examine the relationships between rsFC alterations and measures of executive function and clinical symptom severity. RESULTS:Patients with FM demonstrated aberrant rsFC of the dorsal ACC (dACC) with the limbic system, notably the amygdala (t = 2.840, SE = 0.942, p = 0.007), parahippocampal gyrus (t = 2.340, SE = 0.905, p = 0.024), and insula (t = 2.159, SE = 0.835, p = 0.036). Subregion analyses further revealed heightened connectivity of the anterior midcingulate cortex (aMCC) with the parahippocampal gyrus (t = 2.737, SE = 1.064, p = 0.009), and increased connectivity of the superior anterior cingulate cortex (supACC) with the insula (t = 2.596, SE = 0.706, p = 0.013) and amygdala (t = 2.398, SE = 0.812, p = 0.021), which were significantly associated with pain severity and depressive symptoms in FM. CONCLUSION:This study revealed specific abnormalities in the rsFC between the dACC and the limbic cortices and subcortical nuclei in FM patients. The heightened connectivity of the aMCC with the parahippocampal gyrus and of the supACC with the insula and amygdala was closely associated with the regulation of emotion and processing of chronic pain.

BACKGROUND:Multisite chronic pain (MCP) and major depressive disorder (MDD) exhibit significant clinical relevance. However, the central nervous system comorbidity mechanism and the shared genetic risk mechanisms remain poorly elucidated. This study aims to systematically investigate the neurobiological and genetic correlation features between MCP and MDD. METHOD:Leveraging a multidimensional genetic framework, we integrated GWAS data for MCP (UK Biobank, UKB), MDD (Psychiatric Genomics Consortium, PGC), and ENIGMA neuroimaging data to investigate their genetic-neurobiological interplay. Initially, genome-wide genetic correlations were evaluated using Linkage Disequilibrium Score Regression (LDSC). Next, the GWAS Pairwise (GWAS-PW) method was employed to identify local genetic association regions, complemented by functional annotation through the FUMA platform. Lastly, Mendelian randomization (MR) mediation models were applied to explore the mediating effects of brain structure. RESULT:LDSC analysis revealed a significant genetic correlation between MCP and MDD (rg = 0.53, P = 4.1 ×10-45). GWAS-PW method identified 18 genomic regions associated with both MCP and MDD. FUMA functional annotation prioritized seven key genes (e.g., DCC and TCF4) implicated in neurodevelopmental and synaptic regulation pathways. Additionally, mendelian mediation analysis of specific brain regions, such as the isthmus cingulate cortex, play a mediating role in the comorbid pathogenesis of MCP and MDD. CONCLUSION:This study revealed that MCP-MDD comorbidity arises from genome-wide shared neurodevelopmental loci, structural abnormalities, and dysregulated coordination among the default mode, central executive, and sensorimotor networks, collectively forming its neurobiological basis.

Numerous studies have demonstrated that COVID-19 is associated with an increased risk of new-onset fibromyalgia (FM), which not only significantly impacts patients’ quality of life but also places a substantial burden on healthcare systems. However, no studies have yet investigated whether COVID-19 vaccination may mitigate the risk of developing new-onset FM in individuals who have survived COVID-19. This study aimed to assess the potential effect of COVID-19 vaccination in reducing the risk of new-onset FM among COVID-19 survivors. We utilized the data resources from the TriNetX platform to compare 90,508 COVID-19 survivors who received the COVID-19 vaccine with 90,508 unvaccinated survivors. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and its corresponding 95

SAPHO syndrome is an inflammatory disorder with bone and cutaneous manifestations, for which whole-body bone scintigraphy (WBBS) is frequently used in diagnosis. The WBBS findings of SAPHO syndromes and secondary bone tumors (SBT) have overlapping features, posing diagnostic challenges. In this multicenter study, we aim to identify different bone and joint involvement patterns between the two disease entities through multiple methods to build machine-learning models and explore interpretable variables. The study included 1,193 patients, of which 593 were diagnosed with SAPHO syndrome and 600 with SBT. LASSO regression, logistic regression, and random forest techniques were applied in the training set to identify significant risk factors. Manual management and other methods were evaluated in the validation set to identify the top-performing model and the most interpretable terms. The study developed a model using 15 manually selected terms and multiple machine learning techniques, which demonstrated high diagnostic accuracy in the G1 dataset for (training AUC 0.934, testing AUC 0.929, accuracy = 88.3%, precision = 88.7%, Recall = 88.3%, F1 score = 0.882). The model was compared with logistic regression and random forest models and showed consistent results in the G2 dataset for external validation (AUC 0.957, Youden index = 0.806, sensitivity = 0.820, specificity = 0.986). The pelvis, femur, and ribs (excluding anterior ribs 1st-5th) and thoracic vertebrae 1st-8th were significant predictors of SBT, whereas the sacroiliac joints, sternum, foot, anterior ribs 1st-5th, and clavicle were indicative of SAPHO. This study assesses the effectiveness of WBBS terms in identifying SBT from SAPHO syndrome and utilizes machine learning to help screen features for patients. The final model demonstrates its dependability, providing a valuable tool for accurate and timely diagnosis.

Rheumatoid arthritis is often a neglected autoimmune disease characterized by inflammation and destruction of the joints leading to pain, swelling and restricted movement, particularly affecting specific population groups and severely reducing the quality of life of patients. Certain risk factors (smoking, diet, infections) contribute to the increased prevalence of the disease in patients, with targeted interventions to alleviate symptoms. Due to the complexity of current medications and the lack of a systematic approach to decision-making, Mesenchymal stromal cells therapy has become increasingly popular in recent years. It plays different roles in different diseases, especially in Rheumatoid arthritis, stromal cells have shown promising therapeutic potential for tissue repair and regeneration, immunomodulation and anti-inflammatory effects. This paper provides a systematic review of our current understanding of the regulatory mechanisms, heterogeneity, and cell engineering modifications of stromal cells from multiple sources.

Acrodermatitis continua of Hallopeau (ACH) is a rare aseptic pustular dermatosis for which clinical guidelines are lacking and treatment is largely based on case reports. Biologically targeted therapies offer new therapeutic ideas, with TNF antagonists such as adalimumab showing promising efficacy in both adults and children.The IL-17 and IL-23 axes play a key role in the pathogenesis of ACH, and anti-IL-17A and anti-IL-23 antibodies have shown therapeutic efficacy. In addition, new therapies such as IL-36 inhibitors and JAK inhibitors are being explored. Although biologics provide a new direction for ACH treatment, their safety and efficacy still need to be confirmed by large-scale clinical studies.

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease with recurrent erythema, scales, and sterile pustules on the palms and soles. Treating PPP in children is difficult due to limited effective therapies, especially as there's a lack of data on upadacitinib use in children under 12.This article reports a pediatric PPP case. The patient had severe, recurring rashes that affected daily activities. Treated with upadacitinib for two months, she showed a significant therapeutic response.

BACKGROUND:Epidemiological and observational studies have indicated an association between Sjögren's syndrome (SS) and Parkinson's disease (PD). However, consistent conclusions have not been reached due to various limitations. In order to determine whether SS and PD are causally related, we conducted a Mendelian randomization study (MR) with two samples.METHODS:Data for SS derived from the FinnGen consortium's R9 release (2495 cases and 365 533 controls). Moreover, data for PD were acquired from the publicly available GWAS of European ancestry, which involved 33 674 cases and 449 056 controls. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between SS and PD. To assess the estimation's robustness, a number of sensitivity studies were performed. To determine the probability of reverse causality, we performed a reverse MR analysis.RESULTS:There was no evidence of a significant causal effect of SS on PD risks based on the MR [odds ratio (OR) = 1.03; 95% confidence interval (CI) = 0.95-1.11; p = .45]. Similarly, no evidence supported the causal effects of PD on SS (OR = 0.92; 95% CI = 0.81-1.04; p = .20). These findings held up under rigorous sensitivity analysis.CONCLUSIONS:MR bidirectional analysis did not reveal any cause-and-effect relationship between SS and PD, or vice versa. Further study of the mechanisms that may underlie the probable causal association between SS and PD is needed.

Fibromyalgia (FM) is a central sensitization syndrome that is strongly associated with the cerebral cortex. This study used bidirectional two-sample Mendelian randomization (MR) analysis to investigate the bidirectional causality between FM and the cortical surface area and cortical thickness of 34 brain regions. Inverse variance weighted (IVW) was used as the primary method for this study, and sensitivity analyses further supported the results. The forward MR analysis revealed that genetically determined thinner cortical thickness in the parstriangularis (OR = 0.0567 mm, PIVW = 0.0463), caudal middle frontal (OR = 0.0346 mm, PIVW = 0.0433), and rostral middle frontal (OR = 0.0285 mm, PIVW = 0.0463) was associated with FM. Additionally, a reduced genetically determined cortical surface area in the pericalcarine (OR = 0.9988 mm2, PIVW = 0.0085) was associated with an increased risk of FM. Conversely, reverse MR indicated that FM was associated with cortical thickness in the caudal middle frontal region (beta = -0.0035 mm, PIVW = 0.0265), fusiform region (beta = 0.0024 mm, SE = 0.0012, PIVW = 0.0440), the cortical surface area in the supramarginal (beta = -9.3938 mm2, PIVW = 0.0132), and postcentral regions (beta = -6.3137 mm2, PIVW = 0.0360). Reduced cortical thickness in the caudal middle frontal gyrus is shown to have a significant relationship with FM prevalence in a bidirectional causal analysis.