ABSTRACT
@#The incidence of orofacial pain is high, and its pathological mechanism is complex. Currently, there is a lack of long-lasting and effective clinical treatment drugs, resulting in a major economic burden to patients and society. Therefore, it is important to develop more durable and effective drugs for treatment. In recent years, substantial evidence has shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) play a vital role in somatic and orofacial pain. Among them, subunit phosphorylation regulated by protein kinases and interactions with partner proteins promote the activation and trafficking of AMPARs and signal transduction to regulate the expression of AMPARs. The increase of GluA1-containing AMPARs promotes calcium ion influx, further activating protein kinases and auxiliary proteins, which forms a self-feedback loop. This is an important mechanism that promotes chronic pain. The expression of AMPARs in the trigeminal nervous system and the spinal cord nervous system overlaps, and the above mechanism may also participate in regulating orofacial pain. However, research on AMPARs in orofacial neuropathic pain or cancer-related pain is relatively insufficient, and more in-depth research is needed in the future. Furthermore, there is a lack of clinical evidence for AMPAR antagonists to treat pain. Understanding the regulatory mechanisms of the activation and trafficking of AMPARs and precisely intervening in the activation and trafficking of AMPARs may provide effective strategies for the development of new analgesics and offer new insights for treating orofacial pain.
ABSTRACT
Objective@#To explore the relative effects of various forms of childhood maltreatment on adolescent anxiety and depression and to explore possible sex difference.@*Methods@#By using convenient sampling method, 6 228 middle school students were selected from 2 middle schools in Chongqing. Self reported questionnaires were used to collect demographic characteristics, childhood maltreatment experiences, anxiety and depression symptoms. The relative weights analysis was conducted to analyze the relationship between childhood maltreatment forms and adolescent anxiety and depression and possible sex differences.@*Results@#The prevalence of physical neglect, emotional abuse, physical abuse, emotional neglect and sexual abuse was 28.2%, 23.7%, 16.0 %, 12.4% and 10.3%, respectively. Among them, emotional abuse had the greatest impact on anxiety and depression ( R 2= 0.12 /0.15), followed by emotional neglect( R 2=0.08/0.11), physical abuse ( R 2=0.02/0.03), sexual abuse ( R 2=0.02/0.01) and physical neglect ( R 2=0.01/0.01). Compared with boys ( R 2=0.09/0.12, R 2=0.06/0.09), emotional abuse ( R 2=0.13/0.16) and emotional neglect ( R 2=0.10/0.13) had greater impacts on anxiety and depression among girls.@*Conclusion@#Psychological maltreatment (including emotional abuse and emotional neglect) in childhood has the greatest influence on anxiety and depression, especially for girls.
ABSTRACT
BACKGROUND: Metastatic melanoma has a high mortality rate and poor survival. This is associated with efficient metastatic colonization, but the underlying mechanisms remain elusive. Communication between cancer stem cells (CSCs) and cancer cells plays an important role in metastatic dissemination. Whether cancer stem cells can alter the metastatic properties of non-CSC cells; and whether exosomal crosstalk can mediate such interaction, have not been demonstrated in melanoma prior to this report. RESULTS: The results revealed that exosomes secreted by highly metastatic melanoma CSCs (OL-SCs) promoted the invasiveness of the low metastatic melanoma cells (OL) and accelerated metastatic progression. miR-1268a was up-regulated in cells and exosomes of OL-SCs. Moreover, OL-SCs-derived exosomal miR-1268a, upon taking up by OL cells, promoted the metastatic colonization ability of OL cells in vitro and in vivo. In addition, the pro-metastatic activity of exosomal miR-1268a is achieved through inhibition of autophagy. CONCLUSION: Our study demonstrates that OL cells can acquire the "metastatic ability" from OL-SCs cells. OL-SCs cells achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-1268a, to the targeted OL cells which in turn augments metastatic colonization by inactivating the autophagy pathway in OL cells.
Subject(s)
Humans , MicroRNAs/metabolism , Exosomes/metabolism , Melanoma/metabolism , Autophagy , Stem Cells , Cell Line, Tumor , Neoplasm MetastasisABSTRACT
@#Objective To analyze the incidence and possible risk factors of the chronic postsurgical pain (CPSP) in patients undergoing cardiac surgery with cardiopulmonary bypass via median sternotomy. Methods A total of 248 cardiac surgery patients (104 males, 144 females with age of 20–74 years) were enrolled in this single-center, prospective observational study. The severity of acute postoperative pain at first 7 days was evaluated by numeric rating scale (NRS) and pain at 30 days after surgery and CPSP at 3 and 6 months after surgery was evaluated with modified brief pain inventory. Results The CPSP at postoperative 6 months occurred in 45.2% (112/248) patients and 24.1% of them suffered moderate to severe pain (NRS≥4). The CPSP at postoperative 3 months occurred in 60.9% (151/248) patients and 25.8% of them suffered moderate to severe pain. Moderate to severe postoperative pain at postoperative 30 days and 3 months, and intraoperative remifentanil infusion were the risk factors of the CPSP at postoperative 6 months. Conclusion CPSP is common in patients undergoing cardiac surgery with median sternotomy. Moderate to severe postoperative pain at 30 days and 3 months, and intraoperative remifentanil infusion can predict the presence of CPSP at 6 months.