The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To observe any effect of aerobic exercise on lipid deposition in the liver and monoacylglycerol O-acyltransferase 1 (MGAT1) signaling in non-alcoholic fatty liver disease (NAFLD).Methods:Male Sprague-Dawley rats were fed a 45% diet fat for 6 weeks, after which they were confirmed to have NAFLD. The rats were then randomly divided into an exercise group, a sedentary group and a diet adjustment group. The exercise and sedentary groups remained on the high-fat diet, but the exercise group underwent 8 weeks of aerobic exercise, while the diet adjustment group returned to a normal diet without any exercise. After the intervention, lipid accumulation in liver tissues was detected by hematoxylin-eosin staining and hepatic steatosis indices were calculated. Liver MGAT1 and the expression of peroxisome proliferator activated receptor γ (PPARγ) protein were detected using western blotting.Results:Liver steatosis indices in the exercise and the diet adjustment groups had decreased significantly after the eight weeks. The expression of MGAT1 protein had decreased significantly in the exercise group and the expression of PPARγ protein had increased significantly. Compared with the sedentary group, no significant changes were observed in the expression of MGAT1 protein in the livers of the diet adjustment group, though their average PPARγ protein expression had increased significantly. Compared with the diet adjustment group, the average liver steatosis index had increased significantly in the exercise group, but the expression of MGAT1 protein had decreased significantly.Conclusions:Aerobic exercise can significantly improve liver lipid deposition in NAFLD, at least in rats. The mechanism may be related to inhibition of the MGAT1 signal pathway. Aerobic exercise may be a rehabilitation intervention for NAFLD patients.

BACKGROUND:Traditionally, forced expiratory volume in one second (FEV1) was used to evaluate exercise response of patients with asthma; however, patients obviously had panting after exercise, so FEV1 was affected commonly. Impulse oscillometry (IOS) is a new technique for measuring respiratory impedance that do not require maximal inspiration and forced expiration.OBJECTIVE: To study airway resistance with IOS before and after exercise in healthy and asthmatic patients and investigate the significance of exercise excitation and IOS assessment.DESIGN: Synchronically non-randomized case contrast study.SETTING: Department of Respiratory Medicine, East Hospital Affiliated to Tongji University.PARTICIPANTS: A total of 14 male patients with bronchial asthma who were regarded as the asthmatic group were selected from Department of Respiratory Medicine of Shanghai East Hospital from January to October 2006. They were in a clinical stationary phase. Another 14 male healthy subjects were selected as the control group and ages of all subjects ranged from 29 to 50 years. All subjects provided the confirmed consent.METHODS: IOS was used to measure basic value of respiratory resistance, and then subjects underwent exercise challenge. Nose of subjects was clipped breathing through mouth. Within 3-4 minutes, heart rate was increased to 90% and maintained for 6 minutes during challenge. Respiratory resistance was repeatedly measured at 1, 5, 10, 15 and 20 minutes after exercise, including airway hyperresponse (AHR), total respiratory resistance, central resistance, peripheral resistance and resonance frequency at 5, 20 and 35 Hz of pulse frequency, elasrtic resistance and inertia resistance (X5 and X35) at 5 and 10 Hz of pulse frequency. In addition, difference of AHR at 5 and 35 Hz was calculated, and change ratios of both Rcentral and Rperipheral were calculated as (highest value after exercise-baseline value)/baseline value × 100%.MAIN OUTCOME MEASURES: Basic value of respiratory resistance by using IOS and exercise challenge test.RESULTS: All 14 patients with bronchial asthma and 14 healthy subjects were involved in the final analysis. Peripheral resistance (Rperiphera) was significantly higher than central resistance (Rcentral) in asthmatic patients (P ＜ 0.01). The maximal increase of respiratory impedance occurred from 5 minutes to 10 minutes after exercise in asthmatics. Resonance frequency (Fres) of asthmatics before and after exercise was significantly increased than that of controls (P ＜ 0.01).Change ratios of Fres from asthmatics were higher than that from control group (P ＜ 0.01). After challenge, R5, R5-R20,Zrespir and X5 from asthmatics changed significantly than that from controls (P ＜ 0.01). The increment change value of After exercise Zrespir increased significantly, because obstruction of small bronchi during expiration and impedance increased abruptly. Air trapping was expressed in VT-Zrespir graph in 57.1% patients. There was no difference in the VT-Zrespir graph of controls before and after exercise.CONCLUSION: The main site of airflow obstruction was in small airways in asthmatics after exercise challenge. The general acceptance of IOS method was good among the asthmatic patients. The airway response of exercise challenge may be assessed more accurately with IOS that do not require a maximal inspiration and forced expiration.