Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

Interstitial lung disease (ILD) is a heterogeneous disease characterized by diffuse pulmonary parenchyma, alveolar inflammation, and pulmonary fibrosis. At present, there are no ideal tools to diagnose and predict the prognosis of ILD. The application of biological markers can assist in the rapid diagnosis of the disease and guide clinical treatment decisions. Therefore, there is an urgent need for reliable, safety and feasible biomarkers to identify disease progression and treatment of interstitial lung disease, so as to achieve timely, accurate and personalized treatment for patients with interstitial lung disease.

Interstitial lung disease (ILD) is a heterogeneous disease characterized by diffuse pulmonary parenchyma, alveolar inflammation, and pulmonary fibrosis. At present, there are no ideal tools to diagnose and predict the prognosis of ILD. The application of biological markers can assist in the rapid diagnosis of the disease and guide clinical treatment decisions. Therefore, there is an urgent need for reliable, safety and feasible biomarkers to identify disease progression and treatment of interstitial lung disease, so as to achieve timely, accurate and personalized treatment for patients with interstitial lung disease.

Objective: To detect the expression of GRHL2 (grainyhead-like-2) in breast cancer tissues and to explore its correlation with clinicopathological characteristics and prognosis of breast cancer (BC) patients，aiming to find new therapeutic target for breast cancer. Method: A total of 88 pairs of BC tissues and corresponding para-cancerous tissues from patients with primary BC that treated and pathologically confirmed at the Second Department of General Surgery, Xinxiang Central Hospital from January 2010 to January 2017 were collected for this study. The expression of GRHL2 in BC tissues and para-cancerous tissues was examined with IHC, and the association between GRHL2 and clinicopathological characteristics of BC patients was analyzed. Moreover, the correlation between GRHL2 and prognosis of BC patients was investigated by analyzing TCGA clinic data for BC. Result: The expression of GRHL2 was significantly higher in BC tissues (75.00%) compared with para-cancerous tissues (36.36%) (P<0.01); Based on the results of GRHL2 expression in 114 cases of normal breast tissues and 1 097 cases of primary breast cancer tissues in TCGA database, the expression of GRHL2 in primary BC tissues was significantly higher than that in normal breast tissues (P<0.01). GRHL2 expression was associated with BC TNM stage,histological grade, HER2 status and lymphnode metastasis status (all P<0.05); TCGA database showed that the RFS of 1 979 BC patients with high GRHL2 expression was significantly shorter than that of the 1 972 cases of BC patients with low GRHL2 expression (HR=1.24, 95%CI:1.11-1.38, P<0.01); GRHL2 expression exerted no significant effect on RFS of TNBC patients or ER+ BC patients (TNBC: HR=1.30，95%CI: 0.89-1.88，P=0.170; ER+: HR=1.17, 95%CI:0.76-1.78， P=0.470); however, the RFS of HER2+ BC patients with high GRHL2 expression was significantly shorter than that of HER2+ BC patients with low GRHL2 expression (HR=1.72, 95%CI:1.11-2.68, P=0.015） . Conclusion：Expression level of GRHL2 was up-regulated in BC tissues, and was associated with BC TNM stage, histological grade, HER2 status and the lymphnode metastasis status. GRHL2 plays an important role in the generation and development of BC, indicating poor prognosis.