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.