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Background Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis. Methods We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods. Results GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA. Conclusion Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases.

In this paper, we investigate the limits of Riemann solutions to the Euler equations of compressible fluid flow with a source term as the adiabatic exponent tends to one. The source term can represent friction or gravity or both in Engineering. For instance, a concrete physical model is a model of gas dynamics in a gravitational field with entropy assumed to be a constant. The body force source term is presented if there is some external force acting on the fluid. The force assumed here is the gravity. Different from the homogeneous equations, the Riemann solutions of the inhomogeneous system are non self-similar. We rigorously proved that, as the adiabatic exponent tends to one, any two-shock Riemann solution tends to a delta shock solution of the pressureless Euler system with a Coulomb-like friction term, and the intermediate density between the two shocks tends to a weighted δ -mesaure which forms the delta shock; while any two-rarefaction-wave Riemann solution tends to a two-contact-discontinuity solution of the pressureless Euler system with a Coulomb-like friction term, whose intermediate state between the two contact discontinuities is a vacuum state. Moreover, we also give some numerical simulations to confirm the theoretical analysis.

Purpose The relationship between coronavirus disease 2019 (COVID-19) and rheumatoid arthritis (RA) remains uncertain. We aimed to assess the association between COVID-19 and RA through immune inflammation. Methods First, we conducted a meta-analysis on the risk of COVID-19 infection, hospitalization rate, and mortality rate for patients with RA. Then, Mendelian randomization (MR) was used to evaluate the causal relationship between COVID-19 and RA, and further analyzed the cytokines and immune cells in COVID-19 and RA. Finally, we obtained microarray datasets of COVID-19, RA patients, and normal controls from the GEO database. And performed functional, pathway enrichment, and immune cell infiltration analysis on differentially expressed genes between each group. Results The meta-analysis results suggested that the hospitalization rate and mortality rate of RA patients infected with COVID-19 were higher than those of the control population. MR analysis showed a positive correlation between COVID-19 infection and RA. We also found that interleukin 13 was associated with RA and COVID-19 infection. CD27 on IgD + CD24 + B cells and CD3 on CD39 + CD8 + T cells are common immune cell phenotypes in two diseases. In addition, COVID-19 function is enriched in immune responses mediated by leukocytes and neutrophils, while RA is significantly enriched in the proliferation of T and B lymphocytes. The results of immune cell infiltration showed that both diseases had more neutrophils and fewer CD8 T cells. Conclusion There are many similarities between COVID-19 and RA in immune inflammatory responses such as cytokines and immune cells. COVID-19 may lead to the development of RA through immune inflammation.

Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving the progressive degradation of the cartilage extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological and pathological processes, particularly in protein degradation. Excess cathepsins levels are reported to contribute to the development of OA. However, the causal relationship between the cathepsin family and knee and hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses to explore this causal association. Our results indicated that elevated serum levels of cathepsin O increase the overall risk of knee OA, while increased serum levels of cathepsin H enhance the risk of hip OA. Conversely, the reverse MR analyses did not reveal a reverse causal relationship between them. In summary, OA in different anatomical locations may genetically result from pathological elevations in different serum cathepsin isoforms, which could be utilized as diagnostic and therapeutic targets in clinical practice.

Purpose We conducted an assessment to investigate the impact of prostate volume on the recurrence of patients with non-muscle invasive bladder cancer (NMIBC). Subsequently, we developed and validated nomograms to accurately evaluate recurrence in NMIBC patients. Additionally, we examined the potential improvement in predictive capability achieved by introducing prostate volume as a variable in the model. Methods We conducted a retrospective analysis, enrolling 555 eligible patients from seven independent medical institutions across China. We first evaluate recurrence-free survival outcomes in patients with varying prostate volumes. Subsequently, we divided patients into a training cohort and an external validation cohort. Univariate and multivariate Cox regression analyses were conducted within the training cohort. Accordingly, two nomogram models with and without prostate volumes were developed. Their performance was compared by concordance index, calibration curves, receiver operating characteristics curves, and decision curve analysis. Furthermore, a risk classification model utilizing the nomogram incorporating prostate volume was developed. Results The 3-year recurrence-free survival was markedly lower in patients with large prostate volumes (> 30 ml) compared to those with relatively small prostate volumes (< 30 ml) ( p  < 0.001). The AUC for the model incorporating prostate volume at 3 years in the training cohort and external validation cohort was 0.828 and 0.811, surpassing the AUC for the model excluding prostate volume at the corresponding intervals, which was 0.796 and 0.778. The 1- and 2-year AUC for the two models also exhibited similar differences. The decision curve analysis results demonstrated the significant superiority of the nomogram incorporating prostate volume over the one without it. Conclusion Our investigation revealed that prostate volume significantly influences recurrence in patients with NMIBC. We successfully developed a more accurate nomogram by introducing prostate volume as a variable and provided new insights to further guide clinical management and individualized treatment of NMIBC patients.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor with unique histological and immunohistochemical characteristics. Malignant renal cell carcinoma is even rarer and its biological behavior is still not clear. We report here a case of malignant PEComa in a male patient. The first symptom of the patient was intermittent hematuria. Ultrasound and computed tomography scan showed a solid mass in the left kidney. Fibrosarcoma was initially diagnosed after radical resection of the tumor. Six years later, the patient had a tumor recurrence and underwent a second operation, through which the diagnosis of renal malignant PEComa was made. Since then, the patient received chemotherapy, a third operation, and interventional treatment because of recurrence and metastasis of the tumor, which prolonged the life of the patient for another 6 years. Malignant PEComa involving the kidney is very rare; it seems to develop slowly but will recur and metastasize. At present, surgical resection remains the best treatment.

Background Research has identified a link between the triglyceride-glucose index (TyG-i) and the risk of mortality in severely ill patients. However, it remains uncertain if the TyG-i affects mortality by influencing heart rate (HR). Methods This study enrolled 3,509 severely ill participants from the Medical Information Mart for Intensive Care (MIMIC-IV) database who had triglyceride, glucose, and HR data upon entering the ICU. Cox regression models were applied to estimate the effect of the TyG-i and HR on 28-day all-cause mortality (ACM) and 28-day in-hospital mortality (IHM). Additionally, Kaplan-Meier (K-M) survival analysis was employed to explore outcome variations among different patient groups. The association of the TyG-i with HR, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) II was explored through linear regression analysis. Subgroup analysis explored potential interactions among patient characteristics, while sensitivity analysis gauged the robustness of the findings. Additionally, mediation analysis was conducted to assess whether elevated HR acts as an intermediary factor linking the TyG-i to both 28-day ACM and 28-day IHM. Results During the 28-day follow-up, 586 cases (16.7%) died from all causes, and 439 cases (12.5%) died during hospitalisation. Cox results showed that individuals with a heightened TyG-i and elevated HR had the highest 28-day ACM (Hazard Ratio 1.70, P -value below 0.001) and 28-day IHM (Hazard Ratio 1.72, P -value below 0.001) compared to those with a reduced TyG-i and HR. The K-M curves showed that individuals with low TyG-i and low HR had the lowest incidence of 28-day ACM and 28-day IHM. The linear analysis results evidenced that the TyG-i was independently connected to HR (beta = 3.05, P -value below 0.001), and the TyG-i was also independently associated with SOFA score (beta = 0.39, P -value below 0.001) and SAPS II (beta = 1.79, P -value below 0.001). Subgroup analysis revealed a significant association in participants without hypertension, the interaction of an elevated TyG-i and HR strongly correlated with a higher 28-day death risk (interaction P -value below 0.05). Furthermore, HR mediated 29.5% of the connection between the TyG-i and 28-day ACM ( P -value = 0.002), as well as 20.4% of the connection between the TyG-i and 28-day IHM ( P -value = 0.002). Conclusion For severely ill patients, the TyG-i is distinctly correlated with HR, and elevated levels of both are strongly connected to greater 28-day ACM and 28-day IHM risks, especially in patients without hypertension. Furthermore, elevated HR mediates the connection between the TyG-i and 28-day mortality.

The mTOR inhibitor everolimus has been approved as a sequential or second‐line therapy for renal cell carcinoma (RCC). However, the development of drug resistance limits its clinical applications. This study aims to address the challenge of everolimus resistance and provide new insights into the treatment of advanced RCC. Here, the cytotoxicity of the DNA methyltransferase 1 (DNMT1) inhibitor SGI‐1027 in inducing cell vacuolation and methuosis is discovered and demonstrated for the first time. Additionally, SGI‐1027 exerts synergistic effects with everolimus, as their combination suppresses the growth, migration, and invasion of renal cancer cells. Mechanistically, apoptosis and GSDME‐dependent pyroptosis triggered by lysosomal membrane permeability (LMP) are observed. The upregulation of GSDME expression and increased lysosomal activity in renal cancer cells provide a therapeutic window for the combination of these two drugs to treat renal cancer. The combination treatment exhibits effective anti‐tumor activity and is well tolerated in a subcutaneous tumor model. Overall, this study validates and reveals the specific cytotoxicity property of SGI‐1027 and its potent synergistic effect with everolimus, offering new insights into advanced RCC therapy and everolimus‐resistance overcoming. Schematic model for cell death induced by SGI‐1027 in combination of everolimus suggested by the present study: SGI‐1027 induces vacuolation by macropinocytosis and inhibits the fusion of vacuoles and lysosomes. Everolimus enhances the process of macropinocytosis and cooperates with SGI‐1027 to induce lysosomal membrane permeability (LMP), subsequently leading to apoptosis and GSDME‐dependent pyroptosis.

A horseshoe kidney is a congenital kidney malformation commonly associated with complications such as hydronephrosis, renal calculi, and infections of the renal pelvis. Renal cell carcinoma is extremely rare in a horseshoe kidney; once it occurs, however, it is intractable because of vascular abnormalities. This is especially true in laparoscopic nephron-sparing surgery, even for tumors of <4 cm in diameter. We herein report a case involving an asymptomatic 65-year-old man with an incidental finding of a 4-cm solid mass near the isthmus of a horseshoe kidney on B-mode ultrasonography. Preoperative computed tomography of the renal artery revealed six arterial vessels supplying the affected kidney. Laparoscopic partial nephrectomy was performed. The outcome of this case suggests that laparoscopic nephron-sparing surgery might be a successful treatment method for a horseshoe kidney but that preoperative vessel evaluation and experienced laparoscopic skills are needed.

Targeting the environment of gas-cooled reactors (800 °C, 1 Mpa), we propose an all-sapphire composite-cavity sensor system for pressure measurement with in-situ temperature compensation. The sensor based on a fully sapphire-based dual-cavity structure and white-light interferometry principle. Decoupling two cavities’ information enables the simultaneous measurement. The high hardness and excellent thermal stability of sapphire ensure the high-temperature resilience. The novel central platform structure of the pressure-sensitive diaphragm enhances the spectrum contrast and measurement accuracy while maintaining high sensitivity. An optimized MEMS wet etching process guarantees superior diaphragm surface roughness and etching rate, and high-temperature wafer-level bonding ensures hermeticity. Furthermore, the adaptive peak-shift correction FFT algorithm is proposed for demodulation, achieving a sub-nanometer theoretical resolution. Experimental results under 0–1.2 MPa and 28–800 °C demonstrate that the system exhibits systematic error better than 0.13% F.S (temperature) and 0.18% F.S (pressure). The stability is better than 0.04% F.S. (temperature) and 0.12% F.S (pressure). The sensing chip remains stable performance after prolonged annealing at 1500 °C followed by cooling. It demonstrates the sensor is suitable for pressure monitoring in 800 °C and the potential of the chip for applications in extreme temperature, such as exceeding 1300 °C in aero-engines.