Background: Abdominal aortic calcification (AAC) pathogenesis is intricately linked with inflammation. The pan-immune-inflammation value (PIV) emerges as a potential biomarker, offering reflection into systemic inflammatory states and assisting in the prognosis of diverse diseases. This research aimed to explore the association between PIV and AAC.Methods: Employing data from the National Health and Nutrition Examination Survey (NHANES), this cross-sectional analysis harnessed weighted multivariable regression models to ascertain the relationship between PIV and AAC. Trend tests probed the evolving relationship among PIV quartiles and AAC. The study also incorporated subgroup analysis and interaction tests to determine associations within specific subpopulations. Additionally, the least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression were used for characteristics selection to construct prediction model. Nomograms were used for visualization. The receiver operator characteristic (ROC) curve, calibration plot and decision curve analysis were applied for evaluate the predictive performance.Results: From the cohort of 3,047 participants, a distinct positive correlation was observed between PIV and AAC. Subsequent to full adjustments, a 100-unit increment in PIV linked to an elevation of 0.055 points in the AAC score (β=0.055, 95% CI: 0.014-0.095). Categorizing PIV into quartiles revealed an ascending trend: as PIV quartiles increased, AAC scores surged (β values in Quartile 2, Quartile 3, and Quartile 4: 0.122, 0.437, and 0.658 respectively; P for trend <0.001). Concurrently, a marked rise in SAAC prevalence was noted (OR values for Quartile 2, Quartile 3, and Quartile 4: 1.635, 1.842, and 2.572 respectively; P for trend <0.01). Individuals aged 60 or above and those with a history of diabetes exhibited a heightened association. After characteristic selection, models for predicting AAC and SAAC were constructed respectively. The AUC of AAC model was 0.74 (95%CI=0.71-0.77) and the AUC of SAAC model was 0.84 (95%CI=0.80-0.87). According to the results of calibration plots and DCA, two models showed high accuracy and clinical benefit.Conclusion: The research findings illuminate the potential correlation between elevated PIV and AAC presence. Our models indicate the potential utility of PIV combined with other simple predictors in the assessment and management of individuals with AAC.

The aim of this study was to compare the efficacy and safety of focused low-intensity pulsed ultrasound (FLIPUS) with pulsed shortwave diathermy (PSWD) in subjects with painful knee osteoarthritis (OA). In a prospective randomized trial, 114 knee OA patients were randomly allocated to receive FLIPUS or PSWD therapy. The primary outcome was the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores. Secondary outcomes included the numerical rating scale (NRS) for pain assessment, time up and go (TUG) test, active joint range of motion (ROM) test, and Global Rating of Change (GRC) scale. Data were collected at baseline, 12 days, 12 weeks and 24 weeks. Patients receiving FLIPUS therapy experienced significantly greater improvements in the WOMAC total scores than patients receiving PSWD therapy at 12 days (mean difference, − 10.50; 95% CI − 13.54 to − 7.45; P = 0.000). The results of the NRS, TUG test, ROM test and GRC scale showed that participants treated with FLIPUS reported less pain and better physical function and health status than those treated with PSWD at 12 days (P = 0.011, P = 0.005, P = 0.025, P = 0.011, respectively). Furthermore, patients in the FLIPUS group showed significant improvements in the WOMAC total scores and NRS scores at 12 weeks (mean difference, − 7.57; 95% CI − 10.87 to − 4.26; P = 0.000 and − 1.79; 95% CI − 2.11 to − 1.47, respectively) and 24 weeks (mean difference, − 6.96; 95% CI − 10.22 to − 3.71; P = 0.000 and − 1.37; 95% CI − 1.64 to − 0.96; P = 0.000, respectively) of follow-up. There were no adverse events during or after the interventions in either group. This study concluded that both FLIPUS and pulsed SWD are safe modalities, and FLIPUS was more effective than PSWD in alleviating pain and in improving dysfunction and health status among subjects with knee OA in the short term.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032735. Registered 08/05/2020, http://www.chictr.org.cn/showproj.aspx?proj=53413.

The current research aimed to verify the effects of erythropoietin (EPO) on vascular calcification under inflammatory conditions and the molecular regulator of vascular calcification induced by EPO. To induce vascular calcification and systemic chronic inflammation in SD rats, EPO was administered intraperitoneally, and 10% casein was injected subcutaneously. The administration period lasted for 20 consecutive weeks. Blood samples were subsequently collected to detect inflammatory factors and vascular calcification. Additionally, high-dose EPOs were applied to stimulate primary vascular smooth muscle cells (VSMCs), and vascular calcification was measured using alizarin red staining, alkaline phosphatase (ALP) activity, and calcium salt quantification. The probe 2’,7’-dichlorofluorescein diacetate (DCFH-DA) was employed to detect cellular reactive oxygen species (ROS) levels. The expressions of bone formation-related protein and anti-calcification protein matrix gla protein (MGP) were determined via Western blot. Compared with the control group, calcium deposits and vascular calcification were increased in the EPO group, tumor necrosis factor-alpha (TNF-α) group and TNF-α+ EPO group, whereas MGP was significantly reduced. Moreover, under the stimulation of TNF-α and EPO+TNF-α, pp38/p38 was increased substantially, the addition of p38 inhibitor SB203580 could significantly reduce calcium deposits and vascular calcification. In vivo experiment, compared with the EPO group, calcium salt deposition and vascular calcification were elevated in the EPO+casein group. The present results revealed that high-dose EPO could cause calcification of the abdominal aorta in rats. The inflammatory response aggravated the vascular calcification induced by EPO via activating p38 and ROS levels. Graphical Abstract

Background: RPN1, also known as ribophorin I (RPN1), is a type I transmembrane protein that plays an important role in glycosylation. However, the effects of RPN1 on cancer progression and immune evasion in breast cancer (BC) have not been identified. Materials and methods: The expression of RPN1 was evaluated using RT-qPCR and immunohistochemistry (IHC). The effects of RPN1 on tumor cells were assessed using RT-qPCR, western blotting, flow cytometry, Cell Counting Kit 8 (CCK-8), colony formation assays, and in vivo experiments. The mechanism by which RPN1 modifies programmed death ligand-1 (PD-L1) and the tumor microenvironment was examined by RT-qPCR, western blotting, co-immunoprecipitation (Co-IP), and flow cytometry. The influence of the transcription factor YY1 on RPN1 expression was revealed using bioinformatics analysis, RT-qPCR, and dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Results: RPN1 is aberrantly expressed in triple-negative breast cancer (TNBC) cells, correlating with increased proliferation and poor prognosis. RPN1 mediates the post-translational modification of PD-L1, enhancing its glycosylation and stability, thus facilitating PD-L1-mediated immune escape and tumor growth. The deletion of RPN1 improves the TNBC microenvironment and enhances the efficacy of anti-PD-1 therapy. Additionally, we uncovered a novel regulatory axis involving YY1/RPN1/YBX1 in PD-L1 regulation, affecting TNBC growth and metastasis. Conclusions: Our preliminary study reveals that targeting RPN1 promotes immune suppression, providing a new potential immunotherapy strategy for TNBC. However, further research is necessary to fully elucidate and understand the specific mechanisms of RPN1 in TNBC and its potential for clinical application.

Clear cell renal cell cancer (ccRCC) is a tumor of high malignancy, which can escape apoptosis. The tumor protein p53-inducible nuclear protein 2 (TP53INP2), known as an autophagy protein, is the essential part for autophagosome formation and sensitizes cells to apoptosis. Our study is aimed at exploring the role of TP53INP2 in ccRCC. We have identified the autophagy-related genes (ARGs) of differential expression in ccRCC patients with the help of the TCGA database by bioinformatics analysis. Our assays of quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were for the determination on the both levels of mRNA and protein. Overexpression of TP53INP2 on cellular proliferation, migration, and apoptosis of ccRCC was verified in the ways of performing CCK-8, wound scrape, transwell and flow cytometry assays in vitro, and a mice tumor model in vivo. Transmission electron microscopy was used to measure autophagy formation. The underlying mechanisms of TP53INP2 on ccRCC were determined via coimmunoprecipitation. TP53INP2 was found highly associated with an outcome of worse overall survival (OS) in Kaplan-Meier curves, and this parameter in ccRCC tissues was also lower than the normal tissues. Overexpression of TP53INP2 inhibited ccRCC cellular proliferation, migration, and invasion, as well as the tumor growth of mice. Those cells treated with autophagy inhibitor chloroquine (CQ) or TP53INP2 increased the apoptosis rate. TP53INP2 promoted autophagy formation and elevated the ratio of LC3 II/LC3 I. However, TP53INP2 did not significantly decrease the p-mTOR level. In addition, TP53INP2 activates the expressions of caspase-3, caspase-8, and PARP. Caspase-8 and TNF receptor associated factor 6 (TRAF6) were found to bind to each other in the presence of TP53INP2. TP53INP2 induces apoptosis in ccRCC cells through caspase-8/TRAF6 pathway, rather than the autophagy-dependent pathway.