Risk factors and assessment of subclinical atherosclerosis in patients with psoriatic arthritis.

OBJECTIVE: To understand the prevalence of subclinical atherosclerosis (SCA) in psoriatic arthritis (PsA) patients; to explore the correlation between PsA combined with SCA and traditional cardiovascular risk factors and disease activity; to compare the role of Framingham Risk Score (FRS) and atherosclerotic cardiovascular disease (ASCVD) scores. METHODS: We included 50 PsA patients who met the CASPAR classification criteria, 50 diabetes patients and 50 healthy people. Clinical data were collected from all patients, minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA), ASCVD, FRS were assessed in patients with PsA, and carotid artery intima-media thickness was measured. RESULTS: The prevalence of SCA in PsA patients was significantly higher than that in healthy controls (44% vs 24%, P<0.05). Smoking, drinking, ASCVD, FRS were the risk factors of PsA with SCA (P<0.05). Psoriasis (PsO) duration, PtGA, VAS and DAPSA were the risk factors for PsA with SCA (P<0.05). FRS and ASCVD scores underestimated SCA risk in PsA patients. CONCLUSION: Compared with healthy controls, patients with PsA have higher prevalence of SCA. High DAPSA is a risk factor for PsA with SCA. Carotid ultrasound can monitor SCA in patients with PsA, improve stratification of cardiovascular risk.

Investigating the value of urinary biomarkers in relation to lupus nephritis histopathology: present insights and future prospects.

Lupus nephritis (LN), a leading cause of death in Systemic Lupus Erythematosus (SLE) patients, presents significant diagnostic and prognostic challenges. Although renal pathology offers critical insights regarding the diagnosis, classification, and therapy for LN, its clinical utility is constrained by the invasive nature and limited reproducibility of renal biopsies. Moreover, the continuous monitoring of renal pathological changes through repeated biopsies is impractical. Consequently, there is a growing interest in exploring urine as a non-invasive, easily accessible, and dynamic "liquid biopsy" alternative to guide clinical management. This paper examines novel urinary biomarkers from a renal pathology perspective, encompassing cellular components, cytokines, adhesion molecules, auto-antibodies, soluble leukocyte markers, light chain fragments, proteins, small-molecule peptides, metabolomics, urinary exosomes, and ribonucleic acids. We also discuss the application of combined models comprising multiple biomarkers in assessing lupus activity. These innovative biomarkers and models offer insights into LN disease activity, acute and chronic renal indices, fibrosis, thrombotic microangiopathy, podocyte injury, and other pathological changes, potentially improving the diagnosis, management, and prognosis of LN. These urinary biomarkers or combined models may serve as viable alternatives to traditional renal pathology, potentially revolutionizing the method for future LN diagnosis and observation.

Asparagine Dependency Is a Targetable Metabolic Vulnerability in TP53-Altered Castration-Resistant Prostate Cancer.

TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that specifically target TP53 alterations. Using transcriptomic and metabolomic analyses, we have shown here that TP53-altered prostate cancer exhibits an increased dependency on asparagine (Asn) and overexpresses Asn synthetase (ASNS), the enzyme catalyzing the synthesis of Asn. Mechanistically, the loss or mutation of TP53 transcriptionally activated ASNS expression, directly and via mTORC1-mediated ATF4 induction, driving de novo Asn biosynthesis to support CRPC growth. TP53-altered CRPC cells were sensitive to Asn restriction by knockdown of ASNS or L-asparaginase treatment to deplete the intracellular and extracellular sources of Asn, respectively, and cell viability was rescued by Asn addition. Notably, pharmacological inhibition of intracellular Asn biosynthesis using a glutaminase inhibitor and depletion of extracellular Asn with L-asparaginase significantly reduced Asn production and effectively impaired CRPC growth. This study highlights the significance of ASNS-mediated metabolic adaptation as a synthetic vulnerability in CRPC with TP53 alterations, providing a rationale for targeting Asn production to treat these lethal prostate cancers. Significance: TP53-mutated castration-resistant prostate cancer is dependent on asparagine biosynthesis due to upregulation of ASNS and can be therapeutically targeted by approaches that deplete intracellular and extracellular asparagine.

The association of an elevated Th/Ts ratio and lupus anticoagulant with symptomatic osteonecrosis in systemic lupus erythematosus patients.

Objective: This study aimed to assess the risk factors for symptomatic osteonecrosis (ON) in systemic lupus erythematosus (SLE) and identify clinical characteristics and laboratory markers for predicting symptomatic ON occurrence in SLE patients. Methods: Seventy (6.0%) of 1175 SLE patients diagnosed with symptomatic ON were included in this study. An equal number of SLE patients without symptomatic ON, matched in terms of age and gender, were enrolled in the control group. Clinical symptoms, routine laboratory examinations, lymphocyte subsets, and treatments of these patients were retrospectively reviewed and compared between the two groups. Logistic regression analysis was employed to identify risk factors associated with symptomatic ON in SLE. Results: Among the 70 cases in the symptomatic ON group, 62 (88.6%) patients experienced femoral head necrosis, with bilateral involvement observed in 58 patients. Bone pain was reported in 32 cases (51.6%), and 19 cases (30.6%) presented with multiple symptoms. Univariate analysis revealed significant differences between the two groups in various factors, including disease duration (months), cumulative steroid exposure time, history of thrombosis, neurological involvement, the number of affected organs, myalgia/myasthenia, and the use of medications such as glucocorticoids, immunosuppressants, aspirin, and statins (P<0.05). Moreover, lupus anticoagulant (LA) levels were significantly higher in the symptomatic ON group than in the control group (P<0.05). Furthermore, notable distinctions were observed in peripheral blood immune cells, including an elevated white blood cell count (WBC), a decreased percentage of Ts cells (CD3+CD8+), and an elevated Th/Ts ratio. Logistic regression analysis revealed that a history of thrombosis, LA positivity, and an elevated Th/Ts ratio remained positive factors associated with symptomatic ON (P<0.05). Conclusion: Decreased Ts cells and changes in the T lymphocyte subset play an important regulatory role in the development of symptomatic ON. A history of thrombosis and LA are associated with an increased probability of symptomatic ON in SLE and may serve as potential predictors.

Urinary biomarkers associated with podocyte injury in lupus nephritis.

The most prevalent and devastating form of organ damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN). LN is characterized by glomerular injury, inflammation, cell proliferation, and necrosis, leading to podocyte injury and tubular epithelial cell damage. Assays for urine biomarkers have demonstrated significant promise in the early detection of LN, evaluation of disease activity, and tracking of reaction to therapy. This is because they are non-invasive, allow for frequent monitoring and easy self-collection, transport and storage. Podocyte injury is believed to be a essential factor in LN. The extent and type of podocyte injury could be connected to the severity of proteinuria, making podocyte-derived cellular debris and injury-related urinary proteins potential markers for the diagnosis and monitoring of LN. This article focuses on studies examining urinary biomarkers associated with podocyte injury in LN, offering fresh perspectives on the application of biomarkers in the early detection and management of LN.

Exfoliation of a Coordination Polymer Based on a Linear π-Conjugated Ligand into an Ultrathin Nanosheet for Glyphosate Sensing.

Owing to the large-scale consumption of pesticides and their potential threats to the environment and human health, the development of sensing materials for pesticides has attracted considerable attention in recent years. In this work, a novel Cd(II)-based coordination polymer (CP) with the formula [Cd(H2O)2(L)]·DMF (Cd-1, DMF = N,N-dimethylformamide, H2L = 4,4'-[(2,5-dimethoxy-1,4-phenylene)di-2,1-ethenediyl]bis-benzoic acid) was synthesized under solvothermal conditions. Structural analysis revealed that coordination between central Cd2+ cations and the ligand L2- formed two-dimensional (2D) networks, which were further assembled by noncovalent hydrogen bonds into a three-dimensional (3D) supramolecular framework. Through ultrasonic treatment in isopropyl alcohol, Cd-1 was exfoliated to afford an ultrathin CP-based 2D nanosheet (Cd-1-NS) with a thickness of less than 1.8 nm. Compared to the bulk materials, the prepared Cd-1-NS exhibited enhanced fluorescence emission properties and superior sensing performance toward glyphosate (Glyph) in water with high selectivity, sensitivity, anti-interference, fast response, and good recyclability via the turn-off effect. The limit of detection (LOD) of Cd-1-NS for Glyph was as low as 41 nM (7 ppb) in the low-concentration range of 0-2.4 µM. In addition, the Cd-1-NS also showed excellent practicability and reliability for the detection of Glyph in real samples, including lake water, tap water, cabbage, and watermelon skin, and could realize the rapid visualized sensing of Glyph residues on the surfaces of vegetables and fruits.

Flexi-EIT: A Flexible and Reconfigurable Active Electrode Electrical Impedance Tomography System.

Electrical Impedance Tomography (EIT) systems have shown great promise in many fields such as real-time wearable healthcare imaging, but their fixed number of electrodes and placement locations limit the system's flexibility and adaptability for further advancement. In this article, we propose a flexible and reconfigurable EIT system (Flexi-EIT) based on digital active electrode (DAE) architecture to address these limitations. By integrating a reconfigurable number of up to 32 replaceable DAEs into the flexible printed circuit (FPC) based wearable electrode belt, we can enable rapid, reliable, and easy placement while maintaining high device flexibility and reliability. We also explore hardware-software co-optimization image reconstruction solutions to balance the size and accuracy of the model, the power consumption, and the real-time latency. Each DAE is designed using commercial chips and fabricated on a printed circuit board (PCB) measuring 13.1 mm × 24.4 mm and weighing 2 grams. In current excitation mode, it can provide programmable sinusoidal current signal output with frequencies up to 100 kHz and amplitudes up to 1 mA p-p that meets IEC 60601-1 standard. In voltage acquisition mode, it can pre-amplify, filter, and digitize the external response voltage signal, improving the robustness of the system while avoiding the need for subsequent analog signal processing circuits. Measured results on a mesh phantom demonstrate that the Flexi-EIT system can be easily configured with different numbers of DAEs and scan patterns to provide EIT measurement frames at 38 fps and real-time EIT images with at least 5 fps, showing the potential to be deployed in a variety of application scenarios and providing the optimal balance of system performance and hardware resource usage solutions.

Corrigendum: High follicle-stimulating hormone level associated with risk of rheumatoid arthritis and disease activity.

[This corrects the article DOI: 10.3389/fendo.2022.862849.].

Nocardia rubra cell-wall skeleton activates an immune response in cervical tissue via stimulating FPR3 to enhance dendritic cell-mediated Th1 differentiation.

Nocardia rubra cell wall skeleton (Nr-CWS) has proven to be a successful medicine for therapy of cervical human papillomavirus infection. The mechanism of action of Nr-CWS is unclear but may involve a stimulatory effect on the host immune system. We previously found that CD4+ T cells were increased in cervical tissue after Nr-CWS treatment. Microarray data from these cervical tissues revealed the significant upregulation of formylated peptide receptor 3 (FPR3). This study aimed to explore the role of Nr-CWS in immunomodulatory based on these findings. Examination of CD4+ T cell subsets in cervical tissue from patients who received Nr-CWS revealed substantial increases in Th1 cytokines and transcription factors. The regulatory effects of Nr-CWS on the function and phenotype of dendritic cells (DCs) were assessed in comparison with the traditional DC maturation inducer lipopolysaccharide (LPS). Similar to LPS, Nr-CWS potently induced DC maturation and interleukin-12 (IL-12) secretion. Differentiation of T cells induced by Nr-CWS stimulated DCs was assessed using the mixed lymphocyte reaction assay. Significant differentiation towards Th1 was evident. Finally, FPR3 expression in DCs in response to Nr-CWS and LPS was measured. Nr-CWS potently upregulated FPR3 expression, while the LPS did not. Silencing FPR3 in DCs reduced Nr-CWS-induced IL-12 production and Th1 cell polarization in co-cultured T cells. The collective findings indicate that Nr-CWS may target FPR3 on the surface of DC cells and activate a Th1-type immune response. The findings clarify the basis of the antiviral immune effects of Nr-CWS on human papillomavirus.

Long-term secular trends in dermatomyositis and polymyositis mortality in the USA from 1981 to 2020 according to underlying and multiple cause of death mortality data.

BACKGROUND: People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data. METHODS: We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis. RESULTS: We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD. CONCLUSION: We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.

Nocardia rubra cell wall skeleton regulates tumour-associated macrophage polarization by reprogramming M2 macrophages into M1 macrophages via STAT1/STAT6 pathways.

Targeted therapy with tumour-associated macrophages (TAMs) has emerged as a new paradigm for immunotherapy of cervical cancer. Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immunotherapeutic agent. In this study, we aimed to explore the effects of Nr-CWS on TAMs and the potential mechanisms. Cervical tissue samples were collected before and after Nr-CWS treatment from patients with high-risk HPV infection and cervical intraepithelial neoplasia (CIN). The effect of Nr-CWS on macrophages in vivo was examined by immunohistochemistry and double-labeling immunofluorescence histochemistry. In vitro experiments were performed using a TAM model established by THP-1 cells under Nr-CWS treatment. We found that Nr-CWS treatment significantly reduced the numbers of total macrophages and M2 macrophages, increased the proportion of M1 macrophages and decreased the proportion of M2 macrophages in cervical tissues. After Nr-CWS treatment in vitro, the expression levels of the M1 macrophage markers were increased, while the expression levels of the M2 macrophage markers were decreased. Nr-CWS treatment also activated STAT1 pathways but inhibited STAT6 pathways. These results indicated that Nr-CWS may improve local immune response and reverse immunosuppression by regulating the M2 to M1 polarization of TAMs via STAT1/STAT6 pathways.

Case report: The first case of concurrent breast myeloid sarcoma and borderline phyllodes tumor with malignant features.

Background: Myeloid sarcoma (MS) is a rare hematological malignancy characterized by the formation of a solid mass of myeloblasts outside the bone marrow, such as in the lymph nodes, skin, or bone. MS may arise de novo or concurrently with acute myeloid leukemia (AML), myeloproliferative neoplasm (MPN), or myelodysplastic syndrome (MDS). MS accounts for less than 1% of extramedullary acute myeloid leukemia cases. Phyllodes tumors (PTs) are a rare fibroepithelial breast tumor that can be benign, malignant, or borderline, and account for less than 1% of all breast cancers. Case presentation: We present a unique case of a 50-year-old woman with both breast MS and borderline PT with malignant features, which presented a diagnostic challenge. The patient initially presented with a mass in her right breast, and the initial fine-needle biopsy revealed the presence of immature myeloperoxidase (MPO)+ myeloid cells consistent with MS. Subsequent pathological analysis of tumor tissues after neoadjuvant radiotherapy and chemotherapy showed a borderline PT with malignant features. Following excision of the tumor, the patient experienced a local recurrence, which was also surgically removed. At 8 months post-surgery, the patient remains free of recurrence under close follow-up. Conclusion: This case highlights the importance of considering the possibility of concurrent malignancies in the differential diagnosis of complex breast masses and underscores the challenges involved in diagnosing and managing such cases. Additionally, we also emphasize the value of neoadjuvant radiotherapy and chemotherapy in MS.

Enhanced stent visualization system for percutaneous coronary intervention in patients with chronic kidney disease: effects on contrast media volume and radiation exposure.

OBJECTIVE: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). BACKGROUND: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD), as they share a similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as the radiation dose; however, few studies have reported the impact on contrast media with the use of ESV systems. METHODS: We retrospectively collected 124 patients with acute coronary syndrome who underwent PCI from May 2020 to July 2021. The patients were divided into the ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters, including contrast media volume, radiation exposure (in Air Kerma-AK and Dose Area Product-DAP), number of cines, cine frames, fluoroscopy and procedure time, were recorded and analysed. RESULTS: The groups were comparable regarding the patient characteristics. There was a significant reduction in contrast media volume (174.7 ± 29.6 ml vs.132.6 ± 22.3 ml, p = 0.0001), radiation exposure (776 (499 - 1200) mGy vs. 1065 (791 - 1603) mGy, p = 0.002 in AK; 43 (37 - 73) Gycm2 vs. 80 (64 - 133) Gycm2, p = 0.030 in DAP) and procedure time (53.06 ± 21.20 min vs. 72.00 ± 30.55 min, p = 0.01) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD. CONCLUSION: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in a subgroup analysis in patients with CKD, and this shows that ESV-guided PCI has the potential to reduce renal impairment and mitigate the progression of CKD for those CHD patients with CKD.

Clinical characteristics and surgical treatment of congenital cystic adenomatoid malformation in adults: the largest cohort of 46 patients.

Background: Congenital cystic adenomatoid malformation (CCAM) is a rare congenital malformation of the lungs, however it lacks a summary of pathognomonic clinical and imaging features in adults. Our study aims to evaluate clinical characteristics and surgical treatment in the largest case series of adult CCAM. Methods: The records of 46 adult patients with CCAM admitted to West China Hospital between February 2009 and March 2019 were reviewed. All patients accepted the surgery and get fully recovered. Data were collected and analyzed regarding patient demographics, medical history, preoperative investigations, intraoperative findings, and postoperative outcomes. Results: The records of 22 men and 24 women were examined. The main systemic and respiratory symptoms included fever, productive cough, hemoptysis, and chest pain. Twenty lesions were found in the right pulmonary lobes and 26 in the left lobes. All CCAM lesions were successfully resected by surgery (35 patients had lobectomies, and the remaining 11 patients underwent wedge resections). Twenty-nine patients underwent video-assisted thoracic surgery (VATS), while 17 patients received posterolateral thoracotomy (PLT). The pathological analysis of surgical specimens revealed 26 cases of pure CCAM lesions and 20 cases of CCAM mixed with other diseases. More than 10% of patients had coexisting pre-malignant or malignant lung lesions. Four patients experienced postoperative complications. No intraoperative and postoperative deaths occurred. Conclusions: Surgical resection remains the preferred approach for adults with CCAM and has satisfied outcomes. Clinicians should be aware of possible coexisting infections and malignancies.

High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and Disease Activity.

Background: The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity. Methods: In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups. Results: Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008). Conclusion: High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.

Therapeutic Potential of Janus Kinase Inhibitors for the Management of Interstitial Lung Disease.

Interstitial lung disease (ILD) refers to a heterogeneous group of diseases characterized by lung fibroblast proliferation, interstitial inflammation, and fibrosis-induced lung damage. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is known to be activated by pro-fibrotic/pro-inflammatory cytokines such as IL-6 and IL-13, whose levels are elevated in ILD. The overexpression of growth factors such as transforming growth factor ß1 in ILD activates the JAK/STAT pathway through classical or non-classical pathways, promotes macrophage activation, increases the release of pro-inflammatory and pro-fibrosis factors, and facilitates fibroblast differentiation into myofibroblasts. These findings implicate that the JAK/STAT pathway plays an important role in the course of ILD. Recent evidence also suggests that JAK inhibition alleviates excessive inflammation and pulmonary fibrosis. Accordingly, the JAK inhibitors may serve as promising drugs for the treatment of JAK/STAT-induced ILD.

Related Risk Factors and Treatment Management of Psoriatic Arthritis Complicated With Cardiovascular Disease.

Psoriatic arthritis (PsA) is a chronic autoimmune inflammatory joint disease related to psoriasis (PsO). The risk of PsA patients with cardiovascular disease (CVD) is significantly higher than that of the general population. At present, the relevant mechanism is not clear, chronic inflammation and traditional cardiovascular risk factors are the most important factors for the increased risk of CVD in PsA patients. Early assessment of the risk of PsA patients with CVD, and active control of the disease activity of PsA patients and intervention of traditional cardiovascular risk factors can delay the progression of CVD risk. This article reviews the epidemiology and pathogenesis between PsA and CVD, and reviews the latest developments in the risk assessment and management of CVD in PsA patients.