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Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high‐priority targets for pharmaceutical treatment of ligament degeneration. Here, single‐cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity. After stringent quality control, high‐quality data were obtained from 32,014 cells. Distinct cell clusters comprising stromal and immune cells were identified in ligament tissues. Among them, we noted that collagen degradation associated with CTHRC1+ fibroblast‐like cells and calcification linked to CRTAC1+ chondrocyte‐like cells were key features of ligament degeneration. SCENIC analysis and further experiments identified ATF3 as a key transcription factor regulating the pathogenesis of CRTAC1+ chondrocyte‐like cells. Typically, immune cells infiltrate localized organs, causing tissue damage. In our study, myeloid cells were found to be inflammatory‐activated, and SPP1+ macrophages were notably enriched in degenerative ligaments. Further exploration via CellChat analysis demonstrated a robust interaction between SPP1+ macrophages and CRTAC1+ chondrocyte‐like cells. Activated by SPP1, ATF3 propels the CRTAC1/MGP/CLU axis, fostering ligament calcification. Our unique resource provides novel insights into possible mechanisms underlying ligament degeneration, the target cell types, and molecules that are expected to mitigate degenerative spinal ligament. We also highlight the role of immune regulation in ligament degeneration and calcification, enhancing our understanding of this disease. [ABSTRACT FROM AUTHOR]

Objective: To construct a prediction model for renal involvement in patients with hyperuricemia (HUA) based on logistic regression analysis, to achieve early risk stratification. Method: In this cross‐sectional study, we collected data from the National Health and Nutrition Examination Survey (NHANES), and constructed a predicted model for renal involvement in HUA patients. The discriminative ability of the model was assessed using the receiver operating characteristic (ROC) curve. Model accuracy was evaluated using the Hosmer‐Lemeshow test and calibration curve, while clinical utility was assessed using decision curve analysis (DCA). Furthermore, internal and external validation cohorts were also applied to validate the model. Results: A total of 1669 patients from NHANES between 2007 and 2010 were included in the final analysis for modeling and validation. Six predictive factors including age, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Cr, Uric Acid (UA), and sex were identified by binary logistic regression analysis for renal involvement in HUA patients and used to construct a nomogram with good consistency and accuracy. The AUC values for the predictive model, internal validation, and external validation were 0.881 (95% CI: 0.836–0.926), 0.908 (95% CI: 0.871–0.944), and 0.927 (95% CI: 0.897–0.957), respectively. The calibration curves demonstrated consistency between the nomogram and observed values. The DCA curves of the model and validation cohort indicated good clinical utility. Conclusion: This study developed a predictive model for renal involvement in hyperuricemia patients with strong predictive performance and validated by internal and external cohorts, aiding in the early detection of high‐risk populations for renal involvement. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry.MethodsHLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27-negative patients with AS were analysed separately, and logistic regression and 'relative predispositional effects' (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility.ResultsAlthough numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA-DQB1*06:02. Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis.ConclusionsThese data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.

Objective: This study aimed to assess the association between Dietary Inflammatory Index (DII) score and death among adults with hyperuricemia. Methods: We collected data from the 2001 to 2018 cohorts of the National Health and Nutritional Examination Survey. Death information was obtained based on death certificate records from the National Death Index through December 31, 2019. The associations between DII score and all‐cause, cardiovascular disease (CVD), and cancer death were investigated by using Cox proportional hazards regression models. Results: We enrolled 7,786 participants with hyperuricemia in this study. The DII score ranged from −4.42 to 4.61. Higher DII score was significantly associated with higher levels of body mass index, glycohemoglobin, glucose, low‐density lipoprotein–cholesterol, and C‐reactive protein (all P < 0.05). During 67,851 person‐years of follow‐up, deaths of 1,456 participants were identified, including 532 CVD deaths and 246 cancer deaths. After adjusting for potential variables, significant higher risk of all‐cause (hazard ratio [HR] 1.18, 95% confidence interval [95% CI] 1.03–1.36, P = 0.01) and CVD (HR 1.30, 95% CI 1.03–1.63, P = 0.02) death was observed for individuals with higher DII scores. Considering the DII score as a continuous variable, the risk of all‐cause and CVD death increases 5% (HR 1.05, 95% CI 1.01–1.08) and 8% (HR 1.08, 95% CI 1.02–1.15) with each one‐unit increment in DII score, respectively. Subgroup analysis indicated that the association between DII score and all‐cause death among participants with hyperuricemia was more significant in males. Conclusion: DII score is found to be positively associated with all‐cause and CVD death of adults with hyperuricemia. Controlling the intake of proinflammatory food might be a potential strategy to reduce the mortality rate. [ABSTRACT FROM AUTHOR]

ObjectiveThe human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS.MethodsWe examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term.ResultsSequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS.ConclusionsParallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.

Objective: To construct a risk prediction model for atherosclerotic cardiovascular disease (ASCVD) in patients with hyperuricemia. Methods: Data in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) (2007–2010). Participants from Huashan Hospital were included as an external validation. Logistic regression analysis was used to explore the relevant factors of ASCVD in patients with hyperuricemia. The discriminability of the model was evaluated using the area under the curve (AUC) statistic of the receiver operating characteristic curve. Hosmer–Lemeshow test, correction curve and decision curve analysis (DCA) were used to evaluate the model. Results: A total of 389 patients collected from the NHANES were included in the final analysis. Logistic regression analysis showed that age, creatinine (Cr), glucose (Glu), serum uric acid (SUA), and history of gout were predictive factors for ASCVD in hyperuricemia (HUA) patients. These predictive factors were used to construct a nomogram. And 157 patients from NHANES were in the internal validation group and 136 patients from Huashan Hospital were in the external validation group. The AUC values of the three groups were 0.943, 0.735, and 0.664. The p values of the Hosmer–Lemeshow test were.568,.600, and.763. The calibration curve showed consistency between the nomogram and the actual observed values. The DCA curve indicated that the model has good clinical practicality. Conclusion: This study constructed the ASCVD risk prediction model for HUA patients, which is beneficial for medical staff to detect high‐risk populations of ASCVD in the early stage. [ABSTRACT FROM AUTHOR]

Objective Spontaneous serum uric acid (SUA) decrease has been found in many patients during acute gout attacks, but its mechanism remains unclear. Methods The spontaneous regulation of SUA during a gout attack and its possible causes were evaluated in patients with gout. The mechanism of the spontaneous SUA decrease was further studied in Caco2 cells and a monosodium urate (MSU)-induced gout model of wild-type mice and ABCG2−/− mice. The urate transport function of intestinal epithelial cells was detected by transwell culture of Caco2 cells. Expression of ATP-binding cassette super-family G member 2 (ABCG2), IL-1β and phosphoinositide 3-kinase (PI3K)/Akt was analysed using real-time PCR, western blotting, or immunofluorescence assays. Results SUA decreased during acute gout attacks in both the gout patients and MSU-induced gouty mice. Increased serum CRP and IL-1β levels were correlated with the SUA decrease. Intestinal uric acid excretion and expression of ABCG2 were upregulated in the mice during acute gout attacks. In the ABCG2−/− mice, intestinal uric acid excretion significantly decreased during gout attacks. In an in vitro study of a transwell culture, ABCG2 and its upstream PI3K/Akt pathway were significantly upregulated in intestinal epithelial cells. However, ABCG2 expression and its associated intestinal uric acid transport were inhibited when PI3K/Akt was blocked by a PI3K inhibitor, LY294002. Conclusions Increased intestinal urate excretion resulted in spontaneous SUA downregulation during acute gout attacks. Inflammation-induced PI3K/Akt activation and ABCG2 expression in epithelial cells might contribute to the upregulation of intestinal uric acid excretion. [ABSTRACT FROM AUTHOR]

In the past ten years, the objective structured clinical examination (OSCE) project team of the Shanghai Medical College of Fudan University has continuously conducted further study on the development and maintenance of standardized patients and their application in teaching. The team carried out a series of randomized controlled studies on the application of standardized patients in OSCEs, and obtained strong theoretical and practical results.