Abstract. To the best of our knowledge, the effect of pre-emptively blocking pain transmission on acute postoperative cognitive dysfunction (POCD) has not yet been assessed. Therefore, the present study aimed to investigate the effect of pre-emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative pain and early cognitive function following total knee arthroplasty (TKA) surgery in elderly patients. CFNB was performed prior to TKA surgery in the preemptive analgesia group (n=30) and following TKA surgery in the control group (n=30). POCD was defined as a two-point reduction in the postoperative score compared with the preoperative score in the mini-mental state examination. The visual analog scale (VAS) was used to evaluate the intensity of pain at rest and during exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia group was significantly lower than in the control group (P<0.01). In the preemptive analgesia group, VAS scores at three days post-surgery were lower than those in the control group (P<0.01). The incidence of POCD on the third postoperative day was slightly lower in the pre-emptive analgesia group compared with the control group. In conclusion, the results demonstrate that pre-emptive analgesia by CFNB may promote the recovery of early cognitive function following TKA in elderly patients. IntroductionPostoperative cognitive dysfunction (POCD) describes the memory and intellectual impairment that occurs in certain individuals during the perioperative period (1,2). A major risk factor for POCD is age; therefore, it is particularly prevalent in the elderly (2). Pain is also considered to be a risk factor for POCD as the areas of the brain involved in pain perception and cognitive control overlap (2,3). Total knee arthroplasty (TKA) has been reported to be one of the most painful orthopedic surgeries (4).Postoperative pain is intensified by sensitization of the pain receptors in the spinal cord and brain (5). This sensitization may be due to a perioperative inflammatory response, in which inflammatory mediators released at the operative site sensitize peripheral pain receptors (6). The ensuing increased nociceptive input to the spinal cord sensitizes the pain receptors there and this sensitization, in turn, sensitizes the pain receptors in the brain.If pain impulses from the operative site were interrupted throughout as well as following surgery, both intra-and postoperative peripheral pain stimuli could be blocked from transmitting to the central nervous system, thus reducing sensitization of pain receptors in the brain. If the occurrence of POCD is associated with the development of this sensitization, as has been suggested previously (6), initiating a blockade of pain transmission prior to, rather than following, surgery may decrease the incidence of POCD.Femoral nerve block (FNB) reduces pain transmission from the TKA operative area (7) and when FNB is administered during TKA, following spinal anesthesia postoperative pain is reduced (4). In tendon graf...
Human epidermal growth factor receptor 2-positive (HER2+) breast cancer, which accounts for 15-20% of all breast cancer, is associated with tumor recurrence and poor prognosis. RAS association domain family protein 1 subtype A (RASSF1A) is a tumor suppressor that is silenced in a variety of human cancers. The present study aimed to investigate the role of RASSF1A in HER2+ breast cancer and the therapeutic potential of RASSF1A-based targeted gene therapy for this malignancy. RASSF1A expression in human HER2+ breast cancer tissues and cell lines was evaluated by reverse transcription PCR and western blot analysis. The associations between tumorous RASSF1A level and tumor grade, TNM stage, tumor size, lymph node metastasis and five-year survival were examined. HER2+ and HER2-negative (HER2-) breast cancer cells were transfected with a lentiviral vector (LV-5HH-RASSF1A) that could express RASSF1A under the control of five copies of the hypoxia-responsive element (5HRE) and one copy of the HER2 promoter (HER2p). Cell proliferation was evaluated by the MTT and colony formation assays. It was found that tumorous RASSF1A level was negatively associated with tumor grade (P=0.014), TNM stage (P=0.0056), tumor size (P=0.014) and lymph node metastasis (P=0.029) and positively associated with five-year survival (P=0.038) in HER2+ breast cancer patients. Lentiviral transfection of HER2+ breast cancer cells resulted in increased RASSF1A expression and decreased cell proliferation, especially under hypoxic conditions. However, lentiviral transfection of HER2-breast cancer cells did not affect RASSF1A expression. In conclusion, these findings verified the clinical significance of RASSF1A as a tumor suppressor in HER2+ breast cancer and supported LV-5HH-RASSF1A as a potential targeted gene therapy for this malignancy.
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