Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

OBJECTIVE To establish and optimize tablets adding mechanism of automatic tablet dispensing machine in the inpatient pharmacy, realize tablets checking and fine management for tablets inventory and expiration date in process of tablets adding, reduce incidence of errors, improve work efficiency, and ensure the safety of tablets use for patients. METHODS Intelligent software combined with barcode scanning technology was used to carry out intelligent intervention on the error-prone link in the process of tablets adding of automatic drug dispensing machine. The error ratio of tablets adding(%), average of daily tablets adding time(min), error ratio of tablets quantity in monthly inventory check(%) were compared before and after intelligent intervention. RESULTS Compared with before optimization, the error ratio of tablets adding decreased from 0.11 % to 0%, average of daily tablets adding time decreased from (96.50±21.84)min to (64.23±19.59)min(P<0.01), which saved 32.27 min on average, and error ratio of tablets quantity in monthly inventory check decreased from (9.42±1.13)% to (3.42±0.88)%(P<0.01) after optimizing the dosing process of the automatic drug dispensing machine. CONCLUSION The optimized process of tablets adding of automatic drug dispensing machine is simple and rapid to operate, which has high accuracy. The tablets inventory and expiration date can be tracked and managed in real time, which ensures the safety of tablets use for patients, promotes development of digital pharmacy management system, and improves quality of pharmaceutical care.

Objective To analyze the 10-year survival outcome and failure patterns for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT),aiming to provide reference for optimized treatment for NPC.Methods Clinical data of 866 patients with NPC receiving IMRT from January 2001 to December 2008 were retrospectively analyzed.Survival analysis was performed using the Kaplan-Meier estimator.Univariate analysis was carried out by log-rank test and multivariate analysis was performed using Cox proportional hazards model.Results The median follow-up time was 132 months.The 10-year local recurrence-free survival (LRFS),distant metastasis-free survival (DMFS),progression-free survival (PFS) and disease specific survival (DSS) were 92.0％,83.4％,75.7％ and 78.6％,respectively.A total of 210 patients died including 124 patients (59.0％) from distant metastasis,which was the primary cause of death,and 47 (22.3％) from local regional recurrence.Independent negative factors of DSS included age＞50 years (P=0.00),LDH ≥ 245 IU/L (P=0.00),Hb＜ 120 g/L (P=0.01),T2-T4 staging (P=0.00),N1-N3 staging (P=0.00) and GTV-nx＞20 cm3(P=0.00).The 10-year LRFS,DMFS and DSS of stage Ⅱ NPC patients did not significantly differ after IMRT alone and chemoradiotherapy (P=0.83,0.22,0.23).For patients with stage Ⅲ NPC,the 10-year LRFS and DSS in the chemoradiotherapy arm were significantly higher than those in the IMRT alone (P=0.01,0.01),whereas no statistical significance was observed in the DMFS between two groups (P=0.14).The overall survival of stage Ⅳa+Ⅳb NPC patients is relatively poor.Conclusions IMRT can improve the long-term survival of NPC patients.Distant metastasis is the primary failure pattern.Patients with stage Ⅰ-Ⅱ NPC can obtain satisfactory survival outcomes after IMRT alone.The addition of chemotherapy can further enhance the LRFS and DSS of stage Ⅲ NPC patients.However,the optimal therapeutic strategy remains to be urgently investigated for stage a+ Ⅳb NPC patients.

Objective To explore the effect of information system management combined with PDCA on negative emotion and quality of life in patients with Parkinson's disease.Methods Totally of 232 patients with Parkinson's disease who were hospitalized in Affiliated Hospital of Ji'ning Medical University from July 2014 to June 2016 were selected and divided into observation group and control group according to the random number table, with 116 cases in each group. The control group was given routine mental health education, while the observation group was treated with the combination of PDCA and nursing intervention on the basis of routine nursing. The scores of depression, cognitive function and quality of life were measured and evaluated at three months after admission.Results At the time of admission, scores of depression showed no significant difference between two groups (t=0.965,P=0.102); after the intervention, the score of depression in the observation group was significantly lower than that in the control group, and the difference was statistically significant (t=3.359, P=0.001). Before the intervention, the score of cognitive assessment scale showed no significant difference between two groups (t=1.254,P=0.068); after the intervention, cognitive function score in the observation group was significantly higher than that in the control group, and the difference was statistically significant (t=4.021, P<0.001). The scores of physiological function, psychological function, social function, environmental adaptability and total quality of life in the observation group were improved significantly higher than those in the control group, and the differences were statistically significant (t=5.274, 4.667, 4.277, 4.148, 3.957;P<0.01).Conclusions Information system management combined with PDCA mode nursing intervention can improve the negative emotions and the quality of life of patients with Parkinson's disease.

Objective To evaluate the influence of pressing technique on the malposition of catheter dur- ing the operation of peripherally inserted central catheter (PICC). Methods Totally, 169 patients with lung cancer were randomly divided into treatment group (n = 88), in which the external and internal jugular veins were pressed at the supraclavicular fossa by the assistant when the catheter was navigated in 25 cm, and control group (n = 81), in which the patients were called to turn their angle of mandible to supraclavicular fossa when the cathe- ter was sent in. Results There were only one patient whose catheter was sent in external jugular vein in treatment group and nine patients whose catheters were sent in external and internal jugular vein in control group. The inci- dence of malposition of catheter was significantly different between two groups (1.1% vs. 11. 1% , X2 =7. 3636, P < 0. 01). Conclusion The pressing technique can reduce the incidence of malposition of catheter into external and internal jugular vein during the operation of PICC.