Identification of cross-talk pathways and PANoptosis-related genes in periodontitis and Alzheimer's disease by bioinformatics analysis and machine learning.

Background and objectives: Periodontitis (PD), a chronic inflammatory disease, is a serious threat to oral health and is one of the risk factors for Alzheimer's disease (AD). A growing body of evidence suggests that the two diseases are closely related. However, current studies have not provided a comprehensive understanding of the common genes and common mechanisms between PD and AD. This study aimed to screen the crosstalk genes of PD and AD and the potential relationship between cross-talk and PANoptosis-related genes. The relationship between core genes and immune cells will be analyzed to provide new targets for clinical treatment. Materials and methods: The PD and AD datasets were downloaded from the GEO database and differential expression analysis was performed to obtain DEGs. Overlapping DEGs had cross-talk genes linking PD and OP, and PANoptosis-related genes were obtained from a literature review. Pearson coefficients were used to compute cross-talk and PANoptosis-related gene correlations in the PD and AD datasets. Cross-talk genes were obtained from the intersection of PD and AD-related genes, protein-protein interaction(PPI) networks were constructed and cross-talk genes were identified using the STRING database. The intersection of cross-talk and PANoptosis-related genes was defined as cross-talk-PANoptosis genes. Core genes were screened using ROC analysis and XGBoost. PPI subnetwork, gene-biological process, and gene-pathway networks were constructed based on the core genes. In addition, immune infiltration on the PD and AD datasets was analyzed using the CIBERSORT algorithm. Results: 366 cross-talk genes were overlapping between PD DEGs and AD DEGs. The intersection of cross-talk genes with 109 PANoptosis-related genes was defined as cross-talk-PANoptosis genes. ROC and XGBoost showed that MLKL, DCN, IL1B, and IL18 were more accurate than the other cross-talk-PANoptosis genes in predicting the disease, as well as better in overall characterization. GO and KEGG analyses showed that the four core genes were involved in immunity and inflammation in the organism. Immune infiltration analysis showed that B cells naive, Plasma cells, and T cells gamma delta were significantly differentially expressed in patients with PD and AD compared with the normal group. Finally, 10 drugs associated with core genes were retrieved from the DGIDB database. Conclusion: This study reveals the joint mechanism between PD and AD associated with PANoptosis. Analyzing the four core genes and immune cells may provide new therapeutic directions for the pathogenesis of PD combined with AD.

The preventive effect of photocrosslinked Hep/GelMA hydrogel loaded with PRF on MRONJ.

BACKGROUND: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. METHODS: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. RESULTS: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). CONCLUSIONS: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ.

Development and experimental verification of a prognosis model for disulfidptosis-associated genes in HNSCC.

Disulfidptosis is a newly discovered cell death pattern that has been less studied in head and neck squamous carcinoma (HNSCC). Exploring the molecular features of different subtypes of HNSCC based on disulfidptosis-associated genes (DAGs) is important for HNSCC. In addition, immunotherapy plays a pivotal role in the treatment of HNSCC. Exploring the sensitivity of immunotherapies and developing predictive models is essential for HNSCC. We analyzed the expression and mutational status of DAGs in 790 HNSCC patients and correlated the dates with clinical prognosis. HNSCC patients were divided into 2 groups based on their DAG expression. The relationship between DAGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm. A disulfidptosis risk model was constructed based on 5 risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed column line plots and performed stem cell correlation analysis and antitumor drug sensitivity analysis. Two different disulfidptosis-associated clusters were identified using consistent unsupervised clustering analysis. Correlations between multilayer DAG alterations and clinical characteristics and prognosis were observed. Then, a well-performing disulfidptosis-associated risk model (DAG score) was developed to predict the prognosis of HNSCC patients. We divided patients into high-risk and low-risk groups based on the DAG score and found that patients in the low-risk group were more likely to survive than those in the high-risk group (P < .05). A high DAG score implies higher immune cell infiltration and increased mutational burden. Also, univariate and multivariate Cox regression analyses revealed that the DAG score was an independent prognostic predictor for patients with HNSCC. Subsequently, a highly accurate predictive model was developed to facilitate the clinical application of DAG scores, showing good predictive and calibration power. Overall, we present a comprehensive overview of the DAG profile in HNSCC and develop a new risk model for the therapeutic status and prognosis of patients with HNSCC. Our findings highlight the potential clinical significance of DAG and suggest that disulfidptosis may be a potential therapeutic target for patients with HNSCC.

Design and Implementation of a Message-Based Regional Telemedicine System to Achieve High Availability and Scalability.

BACKGROUND: Different levels of telemedicine systems have been built across China. To share high-quality medical resources and conduct centralized management of telemedicine systems, a regional telemedicine system (RTS) (such as a provincial level system) has been developed to integrate with small-scale telemedicine systems. Although the established systems offer integration services, they are tightly coupled systems, and not easily integrated with new systems. Meanwhile, with the increasing of input/output, it is difficult for them to run with high scalability, considering the cost of architecture redesign and further development. This article presents the design and implementation of regional integration system through a study in Henan, China, mainly aimed to integrate with heterogeneous small-scale telemedicine systems and provide high efficiency. METHODS: A provincial telemedicine system and some city-level telemedicine systems have already been established. The provincial system has been built to act as a regional integration system to connect city-level systems. Adopting message-based technology, the provincial system achieves high availability and high scalability, respectively, through LevelDB + ZooKeeper and multicast. RESULTS: The system achieved the centralized management of established telemedicine systems without restructuring their framework, improving high availability of RTS when one ActiveMQ service node in a group failed, and it did not negatively influence normal business logic when adding a new service node. At the same time, two "Master" state ActiveMQ service nodes provided services simultaneously, which enable the RTS to achieve high scalability. CONCLUSIONS: The message-based regional integration system enriched the RTS with high availability, easy extensibility, and provided a convenient way to integrate new small-scale telemedicine systems.

[Perindopril and losartan attenuate intrahepatic Toll-like receptor 4 protein expression in rats with bile duct ligation-induced hepatic fibrosis].

OBJECTIVE: To investigate the expression of Toll-like receptor 4 (TLR4) in the liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and evaluate the inhibitory effects of perindopril and losartan on TLR4 expression. METHODS: Male Wistar Rats were randomly divided into sham-operated group (n=6), BDL group, perindopril treatment group (2 mg/kg) and losartan treatment group (50 mg/kg) (n=12). Perindopril and losartan groups were further divided into two subgroups for corresponding treatments by gastric lavage once daily for 14 and 30 days. The protein level of TLR4 in the liver tissue was examined by Western blotting. RESULTS: In 14-day BDL group, the protein level of TLR4 significantly increased to 6.53∓1.11 folds of that in the sham group (P<0.05), and was lowered significantly to 1.71∓0.41 folds and 0.95∓0.38 folds following perindopril and losartan treatments for 14 days. TLR4 expression significantly increased to 6.51∓0.87 folds and 5.64∓0.87 folds of that of the sham group in perindopril and losartan groups after the 30-day treatments (P<0.05). CONCLUSION: TLR4 expression is up-regulated in the liver of rats with BDL-induced hepatic fibrosis, and can be lowered by perindopril and losartan treatmemts for 14 days.