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

OBJECTIVE: To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey. METHODS: Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members. RESULTS: Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet. CONCLUSION The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.
Adult ; Asian Continental Ancestry Group ; Heterozygote ; Humans ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics ; Spastic Paraplegia, Hereditary ; genetics

Objective To investigate the correlation between diabetic distress and coping styles among patients with type 2 diabetes. Method One hundred inpatients with type 2 diabetes were engaged in the investigation of their diabetes distress and coping styles by the diabetes distress scale (DDS) and medical coping modes questionnaire (MCMQ) and the correlation between them. Results The average score of diabetic distress was (2.17 ± 0.71), which was at mild level. 57%of them were at the higher level of diabetic distress. Confrontation and avoidance dimensions were lower than the norm in coping styles, and the acceptance dimension was higher than the norm (all P<0.01). The average scores of diabetic distress, regimen-related distress and physician-related distress subscales were negatively correlated with confrontation (all P<0.05). The average score on diabetic distress and the subscales were positively correlated with avoidance and acceptance dimension (all P<0.01). Conclusions Diabetic distress is prevalent in type 2 diabetic patients and the degree of positive coping is still not insufficient. The diabetic distress is negatively correlated to the confrontation, and positively correlated to the avoidance and the acceptance dimension. The medical staff should instruct the patients to adopt positive coping styles, and avoid negative coping styles to reduce diabetic distress. It will be conductive to the physical and mental rehabilitation of the patients as well.

Objective To evaluate the effects of midazolam pretreatment on inflammatory responses and cell apoptosis during intestinal ischemia-reperfusion (I/R) in mice.Methods Thirty healthy male Kunming mice,weighing 18-22 g,were equally and randomly divided into 3 groups using a random number table:sham operation group (S group),I/R group,and midazolam pretreatment group (M group).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 20 min followed by reperfusion.In group M,midazolam 1 mg/kg was injected intraperitoneally,and intestinal I/R was produced 30 min later.At 24 h of reperfusion,the mice were sacrificed,and intestinal tissues were removed for microscopic examination and for determination of the expression of interleukin-6 (IL-6),tumor necrosis factor-alpha (TNF-α) and caspase-3.Intestinal damage was assessed and scored according to Chiu.Results Compared with group S,Chiu's scores were significantly increased,and the expression of IL-6,TNF-α and caspase-3 was significantly up-regulated in I/R and M groups (P＜0.05).Compared with group I/R,Chiu's scores were significantly decreased,and the expression of IL-6,TNF-α and caspase-3 was significantly down-regulated in group M (P＜0.05).Conclusion Midazolam pretreatment can reduce intestinal I/R injury,and the mechanism is related to inhibition of inflammatory responses and cell apoptosis in mice.