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 summarize the major risk factors of infection in the process of cleaning and disinfection of endoscopy center in our hospital,and formulate the corresponding prevention measures to reduce the incidence of endoscopic infection so as to ensure medical safety of patients.Methods:The specialist check the cleaning disinfection process,statistics of each link in the risk factors of infection.600 endoscopes were taken at random after disinfection,endoscopic inner cavity and the outer surface samples are collected,the cleaning and disinfection of the test results for evaluating quality indicators.Results:Testing 600 samples of qualified 584,and the percent of pass is 97.3％,gastroscopy,colonoscopy,duodenum mirror,bronchoscope,endoscopic ultrasonography qualified rate was 98.6％,96.8％,95.6％,96.0％,97.2％,respectively.28 strains of pathogenic bacteria were detected in 16 cases of unqualified samples,including 13 strains of helicobacter pylori,7 strains of escherichia coli,4 strains of pseudomonas aeruginosa,2 strains of pseudomonas aeruginosa,1 strains of staphylococcus aureus,1 strains of Klebsiella pneumoniae;16 cases to detect unqualified reason analysis,scrub incomplete accounted for 37.5％,Not according to the instructions required to use multi-enzyme and disinfectant accounted for 18.75％,special infected patients did not do special treatment of endoscopy accounted for 12.5％,endoscopic insufficient drying and the staffhand hygiene is not up to standard accounted for 12.5％,respectively.Conclusion:Endoscopic cleaning and disinfection aspects of infection caused by many factors,infection control education should be strengthened for all personal in the endoscopy center,regular professional training of cleaning and sanitation personal,cleaning and disinfection process should be standardized management,establish traceability registration system,control the quality of the endoscope cleaning and disinfection from each link.It is the main measure to prevent digestive endoscopy center in infection.

OBJECTIVE:To study inhibitory effect of Lycianthes biflora polysaccharide on the proliferation of hepatic stellate HSCs-T6 cells in rats and its mechanism. METHODS:After treated with 0(blank control),50,100,200μg/ml L. biflora polysac-charide for 24 and 48 h,the activity of hepatic stellate HSCs-T6 cells in rats was determined by MTT assay and inhibitory rate of cell proliferation was calculated;the content of Hyp in supernatant was detected by immunohistochemical assay. After 48 h,the ex-pression of cellular α-smooth muscle actin(α-SMA)was measured by immunohistochemical assay;both transforming growth fac-tor β1(TGF-β1)and Smad3 were measured by Western blot assay. RESULTS:Compared to blank control,50,100 and 200 μg/ml L. biflora polysaccharide could inhibit the proliferation of HSCs-T6 cells;cell inhibitory rates were 39.84%-69.31% and 45.16%-82.93% respectively after treated for 24 and 48 h,which were positively associated with time and concentration. The con-tents of Hyp in supernatant were 178.36-93.25 μg/ml and 131.94-68.74 μg/ml respectively after treated with different concentrations of PRP for 24 and 48 h,which were negatively associated with time and concentration. The protein level of TGF-β1 and Smad3 de-creased after treated with L. biflora polysaccharide for 48 h(P<0.01). CONCLUSIONS:L. biflora polysaccharide can inhibit the proliferation of hepatic stellate HSCs-T6 cells in rats,and its mechanism is associated with the inactivation of endogenous TGF-βpathway for reducing collagen production.