With the rapid development of biotechnology, therapeutic peptide has been a hot area in the central nervous system drugs due to its features of easy to design and target specificity. However, therapeutic peptide is difficult to cross the blood brain barrier into the central nervous system and target cells, coupled with its in vivo instability, which seriously restricts its application in central nervous system diseases. This review focuses on the progress of therapeutic peptides across the blood brain barrier targeting the central nervous system, compares and analyses the methods of increasing therapeutic peptides penetration, specificity and stability in combination with other molecules, in order to provide help for the development of central nervous system drugs.

Objective:To retrospectively analyze the long-term survival (10-15 years) and late toxicity of nasopharyngeal carcinoma (NPC) patients after intensity-modulated radiotherapy (IMRT), aiming to provide reference for the optimal treatment of NPC.Methods:132 patients with NPC who were treated with IMRT in Sichuan Cancer Hospital from 2003 to 2009 were recruited. Among them, 3 patients were classified as stage Ⅰ, 22 cases of grade Ⅱ, 61 cases of grade Ⅲ, 43 cases of Ⅳ A and 3 cases of Ⅳ B, respectively. The median dose was 73.37Gy (66 to 85Gy), divided into 33 times. Twenty patients received radiotherapy alone, 112 cases of concurrent radiochemotherapy. The survival rate was calculated by Kaplan-Meier method and log- rank test. Univariate prognostic analysis was performed. Cox model was used to conduct multivariate prognostic analysis. The late radiation toxicity was evaluated by RTOG/EORTC criteria. Results:The median follow-up duration was 128 months (range, 3 to 191 months). The 10-and 15-year local control rates of NPC patients were 86.0% and 79.9%. The disease-free survival rates were 72.5% and 63.2%, and the overall survival (OS) rates were 65.2% and 57.1%. The local recurrence rate was 12.1%, and the distant metastasis rate was 16.7%. A total of 53 patients died, of whom 15 patients died of local recurrence, 20 patients died of distant metastasis and 18 patients died of other diseases (pneumonia, intracranial hemorrhage and accident, etc.). The 10-and 15-year non-tumor-related mortality rates were 11.3% and 13.6%. Univariate analysis showed that age, smoking habit, lactate dehydrogenase (LDH), T stage and clinical stage were the independent prognostic factors of OS in NPC patients. Multivariate analysis demonstrated that LDH, T stage and synchronous chemotherapy were the prognostic factors of OS in NPC patients. The incidence of gradeⅠ-Ⅱ late radiation injury (hearing impairment, dysphagia, dental caries and xerostomia) was 90.4%, and 8.5% for grade Ⅲ-Ⅳ late radiation injury (skin fibrosis, hearing impairment and radiation brain injury).Conclusions:The 10-and 15-year OS of NPC patients treated with IMRT is relatively high. With the prolongation of survival, the non-tumor-related mortality rate is increased. Distant metastasis is the main cause of treatment failure. The main late injuries include grade Ⅰ/Ⅱ hearing impairment, dysphagia, dental caries and xerostomia.

Objective:To explore the effects of general anesthesia and combined spinal and epidural anesthesia on inflammatory factors and pain in patients with osteoarthritis after total knee arthroplasty.Methods:A total of 84 patients with osteoarthritis who underwent unilateral total knee arthroplasty in Hulunbuir People's Hospital from January 2020 to May 2021 were selected as the research subjects. They were randomly divided into general anesthesia group (40 cases) and combined spinal and epidural anesthesia group (44 cases). Venous blood samples of 5 ml were collected before operation and 6, 24, 48 hours after operation, and the contents of inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6] in serum were determined by enzyme-linked immunosorbent assay (ELISA). The visual analogue pain scale (VAS) of the two groups at 30 min, 6, 24 and 48 hours after operation was compared.Results:At 6 and 24 hours after operation, TNF-α, IL-1β and IL-6 levels in the combined spinal and epidural anesthesia group were lower than those in the general anesthesia group ( t = 4.17, 3.85, 8.95, 10.98, 10.04, 9.87, P < 0.05). There were significant differences in the levels of TNF-α, IL-1β and IL-6 at different time points between the general anesthesia group and combined spinal and epidural anesthesia group ( F = 271.67, 149.26, 81.70, 189.36, 102.44, 157.32, P < 0.001). At 6 and 24 hours after operation, the VAS scores of patients in the combined spinal and epidural anesthesia group were significantly lower than those in the general anesthesia group ( t = 6.60, 3.66, P < 0.05). There were statistically significant differences in VSA scores between the two groups at different time points ( F = 67.47, 52.37, P < 0.05). Conclusion:The effect of combined spinal and epidural anesthesia is significantly higher than general anesthesia in inhibiting the expression of TNF-α, IL-1β and IL-6 in patients with osteoarthritis after operation, and the effect of analgesia is obvious.